Post on 16-Oct-2021
3/28/2019
1
Disclosure
Kevin Schleich reports no actual or potential conflicts of interest associated with this
presentation.
www.google.com/images_cheech&chong
Objectives• Review historical context of medical cannabis and literature
that addresses efficacy of cannabis for multiple medical conditions
• Discuss safety concerns from both an acute and chronic use standpoint
• Compare and contrast available formulations of medical cannabis in Iowa
• Highlight the process by which patients in Iowa can receive medical cannabis
• Summarize the Department of Family Medicine’s (DFM) policy on medical cannabis
3/28/2019
2
Weed 101
• Marijuana contains numerous extractable substances– Steroidal components
– Volatile compounds
• 60 cannabinoids can be isolated– Delta‐9‐tetrahydrocannabinal (THC): main psychoactive cannabinoid
• Dronabinol (Marinol®)
– Cannabidiol (CBD): main non‐psychoactive cannabinoid
• Agents non FDA‐approved in US, but currently investigational (Nabiximol®, Sativex®, Epidiolex®)
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations.
Weed 101
• Two main cannabinoid receptors throughout the human body– CB1: brain, spinal cord, some periphery
– CB2: intestinal tract, peripheral organs, immune system
• Neither CBD or THC directly agonize
either the CB1 or CB2 receptor– THC a partial agonist of CB1
– CBD influences endogenous cannabinoids
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations..http://sensipharma.com/ecs
Weed 101
• CBD antagonizes the effects of THC at the CB1 receptor
• CBD + THC
– Pain relief
– Anti‐spasmodic
• CBD only
– Epilepsy
www.analyticalcannabis.com
THC
CBD
THC + CBD
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations.
3/28/2019
3
Iowa Qualifying Conditions• Cancer, AIDS/HIV, or any terminal illness if:
– Severe/chronic pain– Nausea/severe vomiting– Cachexia or severe wasting
• Neuromuscular disorders:– Multiple sclerosis (with severe/persistent muscle spasms)– Amyotrophic lateral sclerosis (Lou Gehrig’s Disease)– Parkinson’s disease
• Seizures (including those characteristic of epilepsy)
• Crohn’s disease
• Untreatable pain – “…any pain whose cause cannot be removed… the full range of pain
management modalities have been used without adequate result”– accounts for ~90% of clientele in legal states
Does the Stuff Work?
www.google.com/images
Efficacy Data
• The National Academies of Sciences, Engineering, and Medicine (NASEM)– “The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research”
– Comprehensive report highlighting the health effects of recreational/therapeutic cannabis use
– Published in 2017
http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspx
3/28/2019
4
Efficacy Data• Chronic Pain
– “…there is substantial evidence that cannabis is an effective treatment for chronic pain in adults”
– NASEM cites 5 systematic reviews (n=2454)• Low‐quality evidence
• 2 studies focused on fibromyalgia
• Pain scores decreased by ~30% on average
– Generally, higher THC content = greater pain relief
– 31 active trials on clinicaltrials.gov
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspxwww.clinicaltrials.gov
Efficacy Data• Cancer‐Associated Symptoms
– Dronabinol and nabilone approved in 1985 for nausea/vomiting (n/v) associated with chemotherapy
– “…conclusive evidence that oral cannabinoids are effective antiemetics…”
• Dronabinol = ondansetron for delayed n/v• No evidence that combined CBD:THC products are effective
– “…insufficient evidence to support or refute the use of cannabinoids for cancer‐associated anorexia‐cachexia
• Limited evidence that cannabinoids can be useful for HIV/AIDS‐related anorexia and weight loss
• Very little primary literature evaluating CBD:THC combinations
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspxwww.clinicaltrials.gov
Efficacy Data• Seizure Management
– “… no or insufficient evidence to support or refute that cannabis or cannabinoids are effective for seizure management”
– NASEM cites 2 systematic reviews (n<50)• Small numbers of patients • Low quality evidence
– Further case series have been published demonstrating 25‐100% reduction in seizure frequency
• 3 current trials active on clinicaltrials.gov
– Most studies used only CBD
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspxwww.clinicaltrials.gov
3/28/2019
5
Efficacy Data
• Multiple Sclerosis (MS) Spasticity– “…substantial evidence that oral cannabinoids are an effective treatment for improving patient‐reported MS spasticity symptoms”
– “… limited evidence for an effect on clinician‐measured spasticity”
– NASEM cites 2 systematic reviews (n=2138)• Reduction (non‐statistically significant) in Ashworth score for spasticity
• Balanced 1:1 ratio of THC/CBD products predominantly used
– 2 active trials on clinicaltrials.gov
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspxwww.clinicaltrials.gov
Efficacy Data• Parkinsonism
– “…insufficient evidence that cannabinoids are an effective treatment for the motor system symptoms associated with Parkinson’s disease or the levodopa‐induced dyskinesias”
– NASEM cites 1 systematic review (n=26)
– Randomized‐controlled trial completed since NASEM publications suggests improvement in quality of life and motor symptoms (n=21)
• CBD alone was main ingredient studied
– 4 active trials on clinicaltrials.gov
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspxwww.clinicaltrials.gov
Efficacy Data• Irritable Bowel Syndrome (IBS)
– “… insufficient evidence to support or refute that cannabis is an effective treatment for IBS”
– NASEM cites only 1 relevant trial (n=36)• No effect of dronabinol on GI transit
– Trial evaluated by NASEM only utilized synthetic cannabinoid, dronabinol
– Some trials have demonstrated symptom improvement• No evidence of anti‐inflammatory effect
– 1 active trial on clinicaltrials.gov
http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspxGastroenterol Hepatol (N Y). 2016 Nov; 12(11): 668–679
3/28/2019
6
Efficacy Data• NASEM addresses efficacy for indications notapproved in the state of Iowa
Herman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspx
Indication Efficacy Statement
Anxiety“…limited evidence that cannabinoids are effective for improving
situational anxiety symptoms”
Sleep disturbances“…moderate evidence that cannabinoids are effective for
improving short‐term sleep outcomes in those with obstructive sleep apnea, fibromyalgia, chronic pain, and MS”
Dementia“…limited evidence that cannabinoids are ineffective for improving
symptoms”
Depression“…limited evidence that cannabinoids are ineffective for reducing
depressive symptoms”
Post‐traumatic stress disorder (PTSD)
“…there is no evidence to support or refute an association between cannabis use and development of PTSD
Condition Efficacy Studied Product(s)
Chronic Pain 1:1 CBD/THC*
Cancer/HIV‐Related Symptoms THC (Dronabinol)
Seizures CBD
MS Spasticity Symptoms 1:1 CBD/THC
Parkinson’s CBD
Irritable Bowel Synthetic cannabinoids
Situational Anxiety CBD
Sleep Disturbances Semi‐synthetic cannabinoids
Dementia Semi‐synthetic cannabinoids
Depression Semi‐synthetic cannabinoids
PTSD Variety
* Higher doses of THC = greater pain controlHerman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations. http://www.nationalacademies.org/hmd/Reports/2017/health‐effects‐of‐cannabis‐and‐cannabinoids.aspx
www.google.com/images
3/28/2019
7
Short‐Term Adverse Effects
• Marijuana inhalation/ingestion
Dry mouth
Nausea/ vomiting
Tachycardia
Hypertension
Short-term memory
impairment
Impaired motor coordination
www.google.com/imagesN Engl J Med. 2014;371(9):879
Paranoia/psychosis
Long‐Term Adverse Effects
Addiction*• 9%: overall• 17%: begin as adolescent• 25‐50%: daily user
Altered brain development*
Worsening educational outcomes*Cognitive
impairment*
Increased risk of chronic psychosis
disordersΩ
Diminished life satisfaction*
Ω = in those with a predisposition to such
disorders
* = effect strongly associated with initial use
in adolescence
Adverse Effects in Studies
CBD Solution Children With Epilepsy(n=213)
> 10% 5‐10% < 5%
Somnolence (21%)Fatigue (17%)
Decreased appetite (15%)Diarrhea (14%)
Increased appetite (7%)Weight gain (6%)Weight loss (5%)Convulsions (5%)
Gait disturbance (5%)
Sedation (3%)
Devinsky, Orrin. 2015,. “Epidiolex (Cannabidiol) in Treatment Resistant Epilepsy”. Washington, DC.www.google.com/images
3/28/2019
8
“Pharmacy stuff… pharmacy stuff… pharmacy stuff…
pharmacy stuff… pharmacy stuff”
www.google.com/images
Pharmacokinetics
InhaledSublingual /Buccal
Trans‐cutaneous
Oral
Absorption
Onset Seconds 5‐15 min ? 60 min
Time to Peak 30 min 4 hours ? 4‐6 hours
Duration 2‐4 hours ? ? > 8 hours
Bioavailability 10‐35%< inhaled> oral
CBD > THC ~5%
Distribution• Distributes readily into well‐vascularized organs (lung, heart, brain, liver)• Chronic use accumulates in adipose tissue• THC highly lipophilic crosses placenta; excreted into breast milk
Metabolism(by CYP enzymes)
THC CYP2C9, CYP3A4 Activemetabolite (2x as potent)
CBD CYP2C19, CYP3A4 Inactive metabolite
Excretion
Route of Elimination Half‐Life
Feces: 70% (5% unchanged)Urine: 30%
THC: 22 hoursCBD, occasional use: 24‐31 hours
CBD, frequent use: 2‐5 days
Ku, Jennifer. (2018). Cannabis Can Do What? Pharmacological Considerations with Cannabinoids.
Drug‐Drug Interactions
www.google.com/images
3/28/2019
9
What Effects CannabisIncrease Cannabinoid
Levels
• Grapefruit
• Azole antifungals
• Clarithromycin
• Amiodarone
• HIV Antivirals
Ku, Jennifer. (2018). Cannabis Can Do What? Pharmacological Considerations with Cannabinoids.
Decrease Cannabinoid Levels
• Rifampin
• Carbamazepine
• St. John’s Wort
• Barbiturates
• Common offenders for drug‐drug interactions when utilizing the CYP enzyme system
• Current manufacturers recommend monitoring efficacy and safety if administering concurrently with above drugs
• No preemptive dose adjustments necessary
What Cannabis Effects
Ku, Jennifer. (2018). Cannabis Can Do What? Pharmacological Considerations with Cannabinoids.
Cannabis Induces Cannabis Inhibits
Enzymes CYP1A2, CYP2B6CYP2C8, CYP2C9, CYP2C19, UGT1A9,
UGT2B7
EffectDecreases efficacy of the following
drugsIncreases efficacy of the following
drugs
Drugs
Neuro/psych:• Duloxetine• Haloperidol• Olanzapine
Musculoskeletal/analgesia:• Cyclobenzaprine• Naproxen• Tizanidine
Opioids:• Methadone
Hormones:• Estradiol
Neuro/psych:• Citalopram• Diazepam• Lamotrigine• Lorazepam
Platelet inhibitors:• Clopidogrel
Musculoskeletal/analgesia:• NSAIDS
Lipid‐lowering:• Fibrates
Anti‐hyperglycemic:• Sulfonylureas
Opioids:• Morphine
www.google.com/images
3/28/2019
10
Products in Iowa
www.medpharmiowa.com/productswww.google.com/images
20:1(CBD:THC)
2:1(CBD:THC)
1:1(CBD:THC)
1:20(CBD:THC)
Capsule 20 mg:1 mg
5 mg:5 mg 0.25 mg:5 mg
0.5 mg:10 mg10 mg:10 mg
1 mg:20 mg
Tincture5 mg:0.25 mg/0.25 mL
~5 mg:5 mg/0.25 mL 0.25 mg:5 mg/0.25 mL25 mg:2 mg/0.25 mL
Cream17.5 mg:8.75 mg/0.5 tsp*
17.5 mg:8.75 mg/0.5 tspΩ
pediatric formulation; * = no scent; Ω = rosemary extract scent
What’s In Recreational?
www.latimes.com/projects/la‐me‐weed‐101‐1hc‐calculator/www.google.com/images
Product Weight/Size THC (mg)
Pretzels 0.18 oz (5 g) 3
Honey 1 tsp: 0.2 oz (7 g) 8
Cookie 0.56 oz (16 g) 10
Gummy Bear 0.09 oz (2.5 g) 25
Green Tea 0.07 oz (1.9 g) 40
Chocolate Bar 1.5 oz (43 g) 200
Brownie 3.5 oz (100 g) 250
Can I Afford This?• Insurance does not cover
– Cash only form of payment accepted (debit coming)
– Credit card not permitted due to “federal regulations”
• Price of all products published on MedPharm website
• Cost obviously varies widely based on dose utilized/product
www.medpharmiowa.com/productswww.google.com/images
3/28/2019
11
www.medpharmiowa.com/productswww.google.com/images
20:1(CBD:THC)
2:1(CBD:THC)
1:1(CBD:THC)
1:20(CBD:THC)
Capsule 20 mg:1 mg
5 mg:5 mg 0.25 mg:5 mg
0.5 mg:10 mg10 mg:10 mg
1 mg:20 mg
Tincture5 mg:0.25 mg/0.25 mL
~5 mg:5 mg/0.25 mL 0.25 mg:5 mg/0.25 mL25 mg:2 mg/0.25 mL
Cream17.5 mg:8.75 mg/0.5 tsp
17.5 mg:8.75 mg/0.5 tsp
20:1(CBD:THC)
2:1(CBD:THC)
1:1(CBD:THC)
1:20(CBD:THC)
Capsule $69.99/30 caps
$49.99/30 caps $33.99/30 caps
$64.99/30 caps$94.99/30 caps
$119.99/30 caps
Tincture$27.99/14 mL
$89.99/14 mL $79.99/14 mL$129.99/14 mL
Cream$79.99/56 g
$79.99/56 g
Cost Example
• 4 kg infant requiring low THC formulation of tincture for seizures– 5 mg CBD:0.25 mg THC/0.25 mL
– 80‐160 mg total CBD/day in a divided dose
– 60 mg twice daily (120 mg/day = right in the middle)
– 3 mL twice daily = 6 mL/day = 180 mL/month
– 13 bottles of tincture would provide 182 mL
– 13 bottles x $27.99/bottle =
$365/monthHerman, Ronald A. (2018). Current Iowa Medical Cannabis Regulations
www.google.com/images
3/28/2019
12
Prescribing Review
Amoxicillin 500 mg Take 2 caps 3 times daily x 10 days
#60 0 refills
www.google.com/images
“Authorizing” Review
You have a condition
Dr. XYZ
My high school degree and 2-week training course leads me to believe your child needs this
dose of cannabis.
www.google.com/images
Application/Registration
• Patients submit a three‐page application to the Iowa Department of Public Health (IDPH) to receive a medical cannabidiol registration card– Available online at IDPH website
– $100 non‐refundable application fee
– $25 non‐refundable reduced application fee for low‐income
• Patient must be > 18 years of age
• Application must have physician (not PA or ARNP) signed attestation
3/28/2019
13
Application/Registration
• MD Attestation Requirements (page 3)– Established patient‐provider relationship with the patient
– Currently the primary care provider of the patient
– Confirmation that the patient suffers from a qualifying condition
– Have counseled patient (including guided patient to IDPH website) about benefits/risks of medical cannabidiol
– Agree to annually evaluate continuing need
Application/Registration• Patient obtains registration card from the Iowa Department of Transportation (DOT)
• As of December 1, 2018, dispensaries were allowed to begin the sale of medical cannabis
Sioux City
Council Bluffs
Windsor Heights
Davenport
Waterloo
www.idph.iowa.gov/cbd/Program‐Data‐and‐Statistics
Iowa Cannabis Statistics(3/25/19)
www.idph.iowa.gov/cbd/Program‐Data‐and‐Statistics
Role in Registry# of People (11/16/18)
# of People (11/30/18)
# of People (1/11/19)
# of People (2/1/19)
# of People (3/25/19)
Issued Cards: # patients with active, DOT‐issued cards
499 663 1197 1361 2170
Healthcare Practitioners:unique # of physicians who have certified patients
325 353 463 505 619
3/28/2019
14
www.idph.iowa.gov/cbd/Program‐Data‐and‐Statistics
Iowa Cannabis Statistics
“pain”= 61%
11/30/19
“pain”= 65%
2/1/19
“pain”= 67%
3/25/19
UIHC Department of Family Medicine (DFM)Policy
1. Licensed physicians in the State of Iowa are able to provide attestation cards to potential legal users of medical cannabis
2. Legal users must have the cards to apply to the Department of Public Health for a medical cannabis registration card
3. All University of Iowa Department of Family Medicine physicians will not provide attestation cards until January 1, 2020
– UI QuickCare PA/ARNP cannot provide attestation cards under current law
4. When declining to fill out the registration form, we should not actively assist in finding another physician or physician group who will fill out the attestation form
5. The January 1, 2020 date is the earliest date this will be considered. This date could be extended pending utilization patterns and distribution complications
DFM Policy Explanation“Medical cannabis contains minimal amounts of
the kind of marijuana that is used for recreational uses, delta‐9‐tetrahydrocannabinol(THC). The kind of marijuana that dispensaries would provide contains both cannabidiol (CBD) and THC. The CBD portion may have some scientific effect on your condition, but opposes the effect of THC. The THC portion is what provides the “high” effect in recreational marijuana, and the amount in medical cannabis is very small, and will be very expensive.
Because of the relative unknowns, cost, and concern for patient safety, our practice has decided to wait for more information until we consider completing your application.”
3/28/2019
15
DFM Policy Rationale• Policy decision is not based on the lack or presence of
legitimate scientific evidence, but instead suggests there is sufficient uncertainty about multiple aspects of prescribing, producing, and dispensing medical cannabis that warrants a watchful waiting approach by our practice
www.google.com/images
Review• Marijuana contains hundreds of substances, including
CBD and THC which have been produced for medical use
• Medical cannabis was able to be distributed to patients as of December 1, 2018
• While efficacy data is present for some indications of medical cannabis, it is lacking for other indications
• Like any substance, medical cannabis does have adverse effects that must be considered
• UIHC DFM will reevaluate the policy of providing attestation for medical cannabis in January 2020
www.google.com/images
Questions? Questions?
3/28/2019
16
www.hawkeyesports.com