The endocannabinoid system and cancer: therapeutic implication
Medical Aspects of CBD - Tallahassee, FL · 2019-09-19 · Medical Aspects of CBD Objectives: 1....
48
Medical Aspects of CBD Board Certified Family Medicine Physician Medical Cannabis Expert and Certifying Physician MediCanna® Academy Compassionate Medical Cannabis Care Clinic, Apollo Beach , FL Hillsborough County Osteopathic Medical Society Trustee and Past-President Florida Osteopathic Medical Association District 10 Trustee Sasha Noe, DO, PhD
Transcript of Medical Aspects of CBD - Tallahassee, FL · 2019-09-19 · Medical Aspects of CBD Objectives: 1....
Medical Aspects of CBD
Board Certified Family Medicine Physician
Medical Cannabis Expert and Certifying Physician
MediCannareg Academy
Compassionate Medical Cannabis Care Clinic Apollo Beach FL
Hillsborough County Osteopathic Medical Society Trustee and Past-President
Florida Osteopathic Medical Association District 10 Trustee
Sasha Noe DO PhD
Award winning research
Who am I and
Why Trust me
Award winning research has
contributed towards the
advancement of the therapeutic
potential for cannabis over the last
two decades
Award winning research has
been referenced worldwide in
numerous scholarly articles and
books along with the great
cannabinoid researchers of our
lifetime
Who am I and
Why Trust me
Portugal
US
US
Germany
Iceland
Australia
US
US
US
US
US
US
Scotland
UK UK
bull International Speaker
Who am I and
Why Trust me
and many morehellip
MY STORY
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Award winning research
Who am I and
Why Trust me
Award winning research has
contributed towards the
advancement of the therapeutic
potential for cannabis over the last
two decades
Award winning research has
been referenced worldwide in
numerous scholarly articles and
books along with the great
cannabinoid researchers of our
lifetime
Who am I and
Why Trust me
Portugal
US
US
Germany
Iceland
Australia
US
US
US
US
US
US
Scotland
UK UK
bull International Speaker
Who am I and
Why Trust me
and many morehellip
MY STORY
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Award winning research has
contributed towards the
advancement of the therapeutic
potential for cannabis over the last
two decades
Award winning research has
been referenced worldwide in
numerous scholarly articles and
books along with the great
cannabinoid researchers of our
lifetime
Who am I and
Why Trust me
Portugal
US
US
Germany
Iceland
Australia
US
US
US
US
US
US
Scotland
UK UK
bull International Speaker
Who am I and
Why Trust me
and many morehellip
MY STORY
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Award winning research has
been referenced worldwide in
numerous scholarly articles and
books along with the great
cannabinoid researchers of our
lifetime
Who am I and
Why Trust me
Portugal
US
US
Germany
Iceland
Australia
US
US
US
US
US
US
Scotland
UK UK
bull International Speaker
Who am I and
Why Trust me
and many morehellip
MY STORY
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
bull International Speaker
Who am I and
Why Trust me
and many morehellip
MY STORY
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
MY STORY
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
bull best-selling author x 3
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
ldquoAs the only known physician in
the US who holds a PhD in this
arena for almost 2 decades it is
my lifersquos goal to educate and
consult with patients physicians
and the industry about medical
cannabis while developing safe
maximally effective therapeutic
applications of cannabis AND
minimizing the use opioids and
other more harmful
pharmaceuticals to improve overall
health and wellnessrdquo
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
The FDA has only approved Epidiolex a CBD extract for the treatment of 2 rare forms of epilepsy (Dravet Syndrome and Lennox-Gastaut Syndrome)
DISCLAIMERS and DISCLOSURES
The potential therapeutic applications of CBD use in this presentation are based on tens of thousands of in-vitro in-vivo and pre-clinical studies as well as limited RCTs
My experience in the field of medical cannabis spans 25 years of conducting cannabinoid research evaluation of the on-going research publications and clinical applications of cannabinoids as well as consulting and recommending cannabinoid
treatment for symptoms of a variety of medical conditions
The information in this presentation has not been evaluated by the FDA and CBD products are not intended to treat cure or prevent any disease
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
What we know about the
Endocannabinoid System (ECS)-CB3
-lsquoOrphan Receptorsrsquo
GPR18 and GPR55
GPR119 - structural
similarity no cross-
reactivity
THC - is a partial
agonist for CB1-R and
CB2-R
CBD is an inverse
agonist for both
receptors
Neuroimmunomodulation 201724183ndash199
CBD
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
ovaries
httpsmcanzorgnzthe-endocannabinoid-system
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Cannabinoid Receptor Expression
CB2
Microglia
dendritic cells
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Overview of the most important potential targets of the
phytoCBs
httpswwwncbinlmnihgovpmcarticlesPMC5686045
bullpCB is evidenced to interact with
only 1 part of the potential targets
bullThe interactions can lead to
opposing biology outcomes
bullTHC - partial CB1 agonist
bullCBD - CB1
antagonistinverse agonist
bullA2A - Adenosine (brain heart lung
spleen)
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
ldquoClassicalrdquo CB1 signaling (green) and beyond examples
for biased agonism and heteromerization
httpswwwncbinlmnihgovpmcarticlesPMC5686045
CB1 Orexin GABA
Dopamine Opioid and
Adenosine
CB2 CXCR4 or GPR55
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
bull at least some part of the ECS is present in virtually every cell type of the human
body
bull and it was shown to be involved in the regulation of a plethora of physiological
processes
bull In the central nervous system (CNS) - these processes include regulation of
appetite pain sensation mood and memory
bull In the peripheral tissues eg bone formation spermatogenesis sebum
production etc and maybe most importantly immune functions (Olah et al 2017)
The Complexity of the ECS
httpswwwncbinlmnihgovpmcarticlesPMC5686045
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
4
Role of CBD
In-vitro and In-Vivo
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
CBD has been shown to exert potent anti-inflammatory and antioxidant effects
CBD pre-treatment attenuated
CBD role as anti-inflammatory and anti-oxidant
bullhigh-glucose-induced mitochondrial superoxide generation
bullNF-kappaB activation
bullnitrotyrosine formation
bull iNOS and
bulladhesion molecules ICAM-1 and VCAM-1 expression
bullmonocyte-endothelial adhesion transendothelial migration of monocytes
and disruption of endothelial barrier function in human coronary artery
endothelial cells (HCAECs)
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
bullis anti-inflammatory anti-oxidative anti-emetic anti-psychotic and neuroprotective
bullA review of 132 original studies by Bergamaschi et al (2011)
bullpsychomotor and psychological functions are not negatively affected
bulldescribes the safety profile of CBD by highlighting that catalepsy is not induced
bullphysiological parameters (heart rate blood pressure and body temperature) are not altered
bullHigh doses of up to 1500thinspmg per day and chronic use have been repeatedly shown to be well tolerated by humans
bullThere is also evidence that CBD may reduce the negative psychotropic effects memory impairment and appetite stimulation anxiety and psychotic-like states of THC while enhancing its positive therapeutic actions
Cannabidiol (CBD)
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Anti-apototic effect of CBD da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of
cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
As an anti-cancer agent Massi Paola et al ldquoCannabidiol as potential anticancer
drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Role in Hepatitis Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic
ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011)
1368-81 doi101016jfreeradbiomed201102021
Potential roles of CBDnot exhaustive
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Role in Cardiac Function Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress
fibrosis and inflammatory and cell death signaling pathways in diabetic cardiomyopathyrdquo Journal of the
American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Role in Immune Modulation Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its
Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functionsrdquo International journal of
molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Role in Astrocyte Activity Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a
Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188 1669 31 Jul 2017
doi103390ijms18081669
Potential roles of CBDnot exhaustive
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by
Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
ldquoTaken together these results suggest that elevated phosphorylation of NOS3
is essential for oxaliplatin resistance The combination of oxaliplatin and CBD
decreased NOS3 phosphorylation which resulted in autophagy by inducing
the overproduction of ROS through mitochondrial dysfunction thus overcoming
oxaliplatin resistance
To summarize NOS3 plays an important role in oxaliplatin resistance and
CBD overcomes NOS-induced oxaliplatin resistance by inducing autophagy
This enhanced autophagy is triggered by mitochondrial dysfunction through a
reduction in SOD2 expression Additionally because CBD can attenuate the
side effects of oxaliplatin our findings suggest that CBD has potential as a new
therapeutic agent to combine with other modalities and drugs to treat CRCrdquo
CBD role as an anti-oxidant in Human Colorectal Cancer cells
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
CASE REPORT Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS
Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
bull CBD has antipsychotic effects
bull It was found to be a safe and well-tolerated alternative treatment for schizophrenia
Effects of CBD in various studies over the last 25 years have indicated benefit in early stage
psychotic disorders
CBD and anti-psychotic effects
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
214 Articles of case reports and RCTs
Dose ranges 600mg to 1500mg CBD
orally per day
ldquoCBD either as monotherapy or added to
regular antipsychotic medication improved
symptoms in patients with schizophrenia
with particularly promising effects in the
early stages of illnessrdquo
CBD and THC mixtures showed positive
effects in reducing short-term withdrawal
and craving in cannabis use disordersrdquo
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Anti-psychotic potential of CBD Neuro-cognitive mechanism
ldquoIn summary results presented here
suggest that altered function of the
insular cortex a core component of the
salience network may underlie
aberrant salience processing and
psychotic symptoms in patients at
clinical high-risk of psychosis and that a
single dose of CBD may attenuate
some of this dysfunction Future studies
need to investigate whether such
effects may underlie the antipsychotic
effects of CBD observed following a
period of treatmentrdquo
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
CBD Role in Mental Disorders
bullNo adverse effects have been reported for cannabidiol as treatment for mental disorders
bullTHC and CBD-based medicines were associated with improvements of several symptoms of mental disorders but not with remission
bullSide effects can occur but severe AEs were mentioned in single cases only
bullThe overall confidence in the evidence is low
bullTo provide reliable treatment recommendations more high-quality RCTs with larger sample sizes are requested
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Anti-inflammatory effects of cannabinoid-based drugs
Nat Rev Immunol 2005 May5(5)400-11
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Acidic form - growing plant
Unstable
Non-psychoactive
More potent than CBD
Decarboxylated when heated
(smoking vaping cooking)
Non-psychoactive
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullIn vivo studies - Exogenous cannabinoids have been shown to decrease host resistance to a variety of infectious agents
bullTHC to mice reported to lessen their ability to resist infection with Listeria monocytogenes and HSV-2
bullmice and guinea pig models of genital herpes have demonstrated an increased incidence of viral lesions and recurrences for animals treated with Δ9-THC
bullcompromise host resistance to Legionella pneumophila Staphylococcus albus Treponema pallidum Friend leukemia virus and Acanthamoeba
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bull In vitro studies using cells of human and rodent origin have demonstrated that cannabinoids alter the functionality of a diverse array of immune cells
bullΔ9-THC and the synthetic cannabinoids CP55940 and HU-210 have been shown to inhibit cell contact-dependent cytolysis of tumor cells that is mediated by macrophages and macrophage-like cells
bull Δ9-THC also has been reported to suppress proliferation of B and T lymphocytes in response to cell-specific mitogens to suppress the cytolytic activity of NK cells
bull inhibit cell-killing activity proliferation and maturation of cytotoxic T lymphocytes (CTLs)
bullaffect immune cell recruitment and chemotaxis to sites of infection andor injury
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Effect of Exogenous Cannabinoids on Host Resistance and Immunity
bullCollective outcome
bullconsistent with these exogenous compounds as playing a role in decreased host resistance to infectious agents
bullThe recognition that select exogenous cannabinoids acted as anti-inflammatory agents and that immune cells also expressed cannabinoid receptors served as an impetus for studies aimed at defining a functional linkage between these two events
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
bullAlthough the endocannabinoid system (ECS) is involved in the regulation of several
physiological processes including sleep and the immune response its role during
infections has not been fully studied
bull It is well known that the use of this drug increases susceptibility to infections because
of the impact on the modulation of the immune system
bull Itrsquos been suggested that both the CB1 and CB2 were involved in the network that mediates
NK cytolytic activity
bullThese and other studies have indicated that cannabinoids not only exert direct effects
on immune cells but also alter the expression of chemokines and cytokines which are
involved in a complex network of cross-signaling among immune cells that plays a critical
role in homeostatic balance between pro-inflammatory (Th1) and anti-inflammatory
(Th2) activities
Role of Cannabinoids in Infection
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Medical Aspects of CBD
Objectives
1 Brief Overview of the Endocannabinoid System2 Discuss Role of Cannabidiol (CBD) in Medical Conditions3 Special considerations with CBD for appropriate safe effective use in patients
Text to 8133246655
FOMA2019
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
bullMonitor closely
bullDosing and routes of administration
bullobservation and directing treatment
bullblood work surveillance
bull Mental Health Disorders and medication interactions - Complicated
bull Cannabis naive vs Non-Naive patients - most medical cannabis patients are
cannabis naive low levels of THC in CBD products can have psychoactive effects
bull Patient co-morbidities chronic and acute conditions infections wounds (post-op
surgical vs chronic)
bull Geriatric and Pediatric approach to treatment compared to other adult treatments
bull Medication interactions in general - important to understand MC metabolism and
how it potentially can interact with other medications
Special considerations with CBD appropriate safe effectiveness use
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Certificate of Analysis
(COA)
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Pesticides
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Pesticides
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Solvents
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Pathogens
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Heavy Metals
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
ReferencesImmunoregulatory Role of Cannabinoids during Infectious Disease Hernaacutendez-Cervantes R Meacutendez-Diacuteaz M Prospeacutero-Garciacutea Oacute Morales-Montor
JNeuroimmunomodulation 201724183-199
Cannabidiol State of the art and new challenges for therapeutic applications Pisanti Malfitano et al 2017 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed28232276
Crystal structures of agonist-bound human cannabinoid receptor CB1 Nature 2017 Jul 27547(7664)468-471 doi 101038nature23272 Epub 2017 Jul 5
Up-regulation of immunomodulatory effects of mouse bone-marrow derived mesenchymal stem cells by tetrahydrocannabinol pre-treatment involving
cannabinoid receptor CB2 Xie Xiao et al 2016 httpswww-ncbi-nlm-nih-govlecomlrclecomedupmcarticlesPMC4872725
Cannabidiol (CBD) and its analogs a review of their effects on inflammation Burstein 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupubmed25703248
Turning Over a New Leaf Cannabinoid and Endocannabinoid Modulation of Immune Function Cabral Rogers Lichtman 2015 httpswww-ncbi-nlm-nih-
govlecomlrclecomedupmcarticlesPMC4469415
The endocannabinoid system and its therapeutic exploitation Di Marzo V1 Bifulco M De Petrocellis L Endocannabinoid Research Group Institute of
Biomolecular Chemistry National Research Council Via Campi Flegrei 34 Comprensorio Olivetti 80078 Pozzuoli Napoli Italy vdimarzoicmibnacnrit Nat
Rev Drug Discov 2004 Sep3(9)771-84
Cannabinoid-based drugs as anti-inflammatory therapeutic Thomas W Klein May 2005 Volume 5 wwwnaturecomreviewsimmunol
Cabral G A and L Griffin-Thomas ldquoEmerging Role of the CB2 Cannabinoid Receptor in Immune Regulation and Therapeutic Prospectsrdquo Expert reviews in
molecular medicine 11 (2009) e3 PMC
Massi P et al Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer
activity Eur J Pharmacol 2000387343ndash347[PubMed]
Klein TW et al Delta-9-tetrahydrocannabinol treatment suppresses immunity and early IFN-gamma IL-12 and IL-12 receptor beta 2 responses to Legionella
pneumophila infection J Immunol 20001646461ndash6466 [PubMed]
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
References
da Silva Vanessa Kappel et al ldquoAntiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron
overloadrdquo Translational psychiatry vol 81 176 3 Sep 2018 doi101038s41398-018-0232-5
Massi Paola et al ldquoCannabidiol as potential anticancer drugrdquo British journal of clinical pharmacology vol 752 (2013) 303-12 doi101111j1365-
2125201204298x
Chronic administration of cannabidiol to healthy volunteers and epileptic patientsCunha JM Carlini EA Pereira AE Ramos OL Pimentel C Gagliardi R
Sanvito WL Lander N Mechoulam RPharmacology 1980 21(3)175-85
Antipsychotic effect of cannabidiol Zuardi AW Morais SL Guimaratildees FS Mechoulam R J Clin Psychiatry 1995 Oct 56(10)485-6
Jeong Soyeon et al ldquoCannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer
Cellsrdquo Cancers vol 116 781 5 Jun 2019 doi103390cancers11060781
Bergamaschi MM Queiroz RH Zuardi AW Crippa JA Safety and side effects of cannabidiol a cannabis sativa constituent Curr Drug Saf (2011) 6237ndash49
doi102174157488611798280924
Rajesh Mohanraj et al ldquoCannabidiol attenuates cardiac dysfunction oxidative stress fibrosis and inflammatory and cell death signaling pathways in diabetic
cardiomyopathyrdquo Journal of the American College of Cardiology vol 5625 (2010) 2115-25 doi101016jjacc201007033
Mabou Tagne Alex et al ldquoA Novel Standardized Cannabis sativa L Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte
Functionsrdquo International journal of molecular sciences vol 208 1833 13 Apr 2019 doi103390ijms20081833
Kozela Ewa et al ldquoModulation of Astrocyte Activity by Cannabidiol a Nonpsychoactive Cannabinoidrdquo International journal of molecular sciences vol 188
1669 31 Jul 2017 doi103390ijms18081669
Mukhopadhyay Partha et al ldquoCannabidiol protects against hepatic ischemiareperfusion injury by attenuating inflammatory signaling and response
oxidativenitrative stress and cell deathrdquo Free radical biology amp medicine vol 5010 (2011) 1368-81 doi101016jfreeradbiomed201102021
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
Sasha Noe DO PhD is a dual
doctorate board-certified award
winning physician researcher best-
selling author speaker and medical
cannabis expert
Dr Noe is
The only known physician in the US
with a PhD in the field of molecular
cannabinoid research
An award-winning published
researcher over the last two decades
contributing towards the advancement
of the therapeutic potential for
cannabis
Has been referenced worldwide in
numerous scholarly articles and
books
wwwdrsashanoecom
FB Group Physicians Only
MediCannareg Docs
httpbitlyMediCannaDocs
DrSashaNoe
Text to 8133246655
FOMA2019
infoDrSashaNoecom
