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Marijuana in a Medical Context

Eric A. Voth, M.D., F.A.C.P-

Chairman

The Institute on

Global Drug Policy

Medical Excuse Marijuana

As with any medication that possesses

significant side effects, it is imperative to

understand that there are important medical,

legal, and social consequences to the use of

marijuana for medicinal applications.

Medical Excuse Marijuana

No compelling evidence that there

is a significant group of untreated

or inadequately treated patients.

Support is vastly anecdotal.

Marijuana lobby getting its

“nose under the tent”

Appropriate Prescribing

Providing reasonable doses of effective

medications to the correct patients in a

manner that is carefully monitored and

which provides the patient with

improvement in daily life functions

Pharmacotherapy

Demonstrated efficacy ***

Predictable dose response ***

Known dose availability ***

Known and predictable side effects ***

Be cautious of reinforcing qualities ***

***Not available with Marijuana.

Scientific Status of Medical

Excuse Marijuana

Specific Cannabinoids may be useful and

worth studying

Smoking problematic/ Doses unpredictable

Legislative processes bypass the FDA and

jeopardize the public

Oral THC (Marinol) is readily available

New products such as Sativex and

Epidiolex are on the horizon/ Also

Investigational New Drug Applications

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Organizations Voicing Positions

NIH 1994

American Public Health Association

1995

AMA 1997

Institute on Global Drug Policy 1997

NIH 1997

WHO 1997

British Medical Association 1997

IOM 1999

Academy of Addiction Psychiatry

2002

AAFP 2007

American College of Physicians

2008

American Academy of

Ophthalmology

American Academy if Pediatrics

2004

American Nurses Association 2008

American Glaucoma Society 2009

American Medical Association 2009

American Psychiatric Association

2009

American Society of Addiction

Medicine 2010

Marijuana

Impurity-over 500 substances, 66

cannabinoids

Resembles tobacco in constituents.

High THC concentrations 2-30%

1/2 life 5-7 days

Ave %THC potency (seizures)

1975 0.74%

1977 0.90

1980 2.06

1983 3.23

1985 2.82

1990 3.35

1992 3.10

1995 3.75

1996 4.07

1997 4.53

1998 4.43

1999 4.55

2000 4.87

2001 5.32

2002 6.34

2003 6.12

2006 8.75

2007 9.6

2008 8.8

University of Mississippi

Potency monitoring report

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THC Potency Proposed Medicinal Uses of

Marijuana

Nausea of Chemotherapy

Glaucoma

Appetite Stimulation

Multiple Sclerosis

Pain

Misc- Cramps, Sleep, Depression

“Any Chronic Condition” wording

Who is Actually Using

Medical Excuse Marijuana?

Under 34 -- 45.4%

Under 54 (most pain age older) 84%

For Pain 82%

For Anxiety 37%

For Depression 26%

For Nausea 27%

For Appetite 37.7%Journal of psychoactive drugs

2011;43:128-135

Nevada Medical Program

65% between 35 and 64 y/o

20% 25-34 y/o

59% complain of pain

21% muscle spasm

12%nausea2012 Nevada State Epidemiologist

Marijuana

For

Pain

Pharmacotherapy

Demonstrated efficacy ***

Predictable dose response ***

Known dose availability ***

Known and predictable side effects ***

Be cautious of reinforcing qualities ***

***Not available with Marijuana.

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Pain

Healthy volunteers doses 0,2,4,8% THC

Decrease of pain medium doses

Increase of pain higher doses

?Specific substance responsible?Anesthesiology. 2007;107:785-96

What is an effective dose?

Evaluation of neuropathic pain

Diabetic, post herpetic, idiopathic,

lumbosacral, brachial plexopathy

Pain reduction similar to level of reduction

with other standard medications.

Massive doses appear unnecessary Wilsey et al

Journal of pain 2013;136-148

Marijuana for Neuropathic pain

38 subjects / # who had 30% reduction

Placebo Medium 3.53 Low 1.29

27% 57% 61%

Significant dose-related effects on memory

and learning

Both groups reported feeling high, stoned,

impaired, medium greater than low dose.

Massive doses appear unnecessary

THC as Opioid Adjunct

THC alone ineffective for the most part

Literature is contradictory. Some

demonstrated higher morphine doses

May be useful as an adjunct to opiods

International Review of Psychiatry,

April 2009; 21(2): 143–151

Palliative Care

Studies largely marginal

Mostly involve oral or Sativex

Not indicated as sole agent

May be some add-on benefitInternational Journal of Palliative Nursing

2010, Vol 16, No 10

Pain in HIV

Trial in HIV-associated neuropathy

No comparison to other medicines nor

Marinol

Benefit in reducing the neuropathic pain

comparable to existing medications

Difficult to discern “high” vs. medical

effect Abrahms Neurology 2007;68 515-521

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Abrahms

Table 2 Mean side effect scores by study group

Anxiety* 0.25 (0.14, 0.44) 0.10 (0.05, 0.22)

Sedation† 0.54 (0.36, 0.81) 0.08 (0.04, 0.17)

Disorientation† 0.16(0.07, 0.34) 0.01 (0.00, 0.04)

Paranoia 0.13 (0.03, 0.45) 0.04 (0.01, 0.14)

Confusion† 0.17 (0.07, 0.39) 0.01 (0.00, 0.06)

Dizziness† 0.15 (0.07, 0.31) 0.02 (0.01, 0.05)

Nausea 0.11 (0.04, 0.30) 0.03 (0.01, 0.14) * p, 0.05; † p 0.001.

HIV Cognitive Impairment

HIV patients vs controls

Significantly more depression and anxiety

in marijuana using group

More alcohol use if used marijuana

Memory impaired even after factoring out

depression, anxiety, and alcohol

The Journal of Neuropsychiatry and

Clinical Neurosciences 2004; 16:330–335

Pain Summary

Summary of literature on pain/ quality of

studies generally marginal

Mostly discussing oral or synthetic

cannabinoids

May be useful as an adjunct particularly for

neuropathic pain

As solo agent, Effective doses undefined. Current Opinion in Anaesthesiology 2005, 18:424–427

Cannabinoids in MS

meta-analysis

All studied were non-smoked

Cannabinoids difficult to work with

Adverse effects not related to dose

Little benefit for spasticity-poss as add-on

Evidence on tremor weak

Evidence on pain moderate

Problems with psychoactivityCNS Drugs 2011:25 Zajicek

MS- Cognitive Effects

MS patients using smoked or ingested pot

Impaired processing speed, memory,

executive function, spatial perception

Twice as likely as nonusers to be

classified as globally cognitively

impaired.

Neurology 2011;76:1153-1160

Complications of marijuana use

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Neuro-Behavioral Implications

Brain Development

Motivation

Emotion

Judgment

Cerebellum

Amygdala

Nucleus Accumbens

Prefrontal Cortex

Judgment is last to develop!

Physical coordination Sensory processing

Maturation starts at the back of the brain

and moves to the front

Complications of Marijuana Use

Cognitive Changes Attention

Concentration

Decision-making

Inhibition

Impulsivity

Working memory

Verbal fluency

Concept formation and planningJ Addict Med 2011;5:1-8

Structural Change on MRI

48 marijuana users

Abnormal Gray Matter volume

Abnormal Orbitofrontal Cortex

Part of the reward network of the brain

Cumulative deleterious effect on OFC Filbey et al

Proceedings of the National Academy of Sciences,

2014;111:16913-16918

Structural Damage to Brain

59 users 33 controls

Ave age 33, Ave use 15 yrs, started 16.7 yo

Ave joints /mo=147

Ave life joints 25922

Demonstrated axonal connectivity

impairment in hippocampus, splenium of

corpus callosum, commissural fibers Brain 2012:135;2245-2255

Neuropsychological Decline

1037 individuals

Pot use at 18,21,26,32,38 y/o

Neuropsych testing at 13 before pot and 38

Broad Neuropsychological decline across all

domains even controlling for education

10% (101-91) IQ difference between never and

persistent user.

6-point IQ decline age 13-38 w/ persistent useProc Natl Acad Sci U S A. 2012 Aug 27

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Poor Life Outcomes with Pot

Never used cannabis vs daily before age 17

Increased odds of :

later cannabis dependence (17·95, 9·44–34·12),

use of other illicit drugs (7·80, 4·46–13·63),

suicide attempt (6·83, 2·04–22·90).

Reductions in:

high- school completion

degree attainment Lancet Psychiatry 2014; 1: 286–93

From the horse’s mouth

“I used to smoke this stuff regulerly I quit because I

needed to pass a test to get a job. The reason I am writing

is because I never had any of thougs side effects you talk

about don’t get me wrong its not for every body. But you

don’t need to say untrue things about it coordination

imparment that’s bs it allows you to focus better on single

things its perfect for kids like I was that cant concetrate on

ting well you don’t have to reply to this email I am just

bored and looking at stuff on the net and emailing people

and going on and on cause I cant sleep well you have a

nice day.

Driving effects Driving Effects

Combining EtOH and Marijuana in First

Study Reduced Driving Skills

.07 + 100ug = Plain EtOH of 0.09

.07 + 200 ug = Plain EtOH of .14 g/dl

NHTSA Notes Annals of Emergency Medicine

2000;35:399

Marijuana and Fatal Crashes

California 2008

Five years following medical excuse

marijuana dispensaries 1240 fatal crashes

compared to 631 for the five years prior

8.3% of fatal single vehicle crashes

5.5% fatal passenger crashes

Use rate estimated at 16-20%

Rivals alcohol as top cause of fatalitiesCrancer and Crancer

Involvement of marijuana in

California Fatal Vehicle Crashes

Medicinal Use and Driving

Impairment Subjects received 10 and 20 mg dronabinol

Worse impairment that 0.05 BAC

Standard Field Sobriety Test was not

abnormal when other findings were

Actual driving tests were affected.

Addiction,107.1837-1844

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Marijuana & Pilots

Psychiatric and

Behavioral Disorders

PTSD and Marijuana Use

2000 participants in VA treatment programs

Non-users had significantly less symptoms

Prior users who quit had less symptoms

Users had higher levels of violence,

New users had higher levels of violence and also

turned more to other drugs

Commented: “Most people assume things based

on their own experience… People assume that

there aren’t a lot of risks…..there really are”Wilkinson

Yale University December 2014

Presented to the AAAP

Depression

Depressive responses measured

Lower doses= Serotonin agonist

Higher doses= Serotonin suppressant

Effect was the Medial Prefrontal Cortex

J Neuroscience 2007;27:11700-11711

Marijuana and Psychosis

Early cannabis use is associated with

psychosis-related outcomes in young adults.

The use of sibling pairs reduces the

likelihood that unmeasured confounding

explains these findings. Further support for

the hypothesis that early cannabis use is a

risk-modifying factor for psychosis-related

outcomes in young adults. Arch Gen Psychiatry. 2010;67(5)

Persistence of Psychosis

Risk of psychosis -no prior psychosis who

used pot, 1.9 times greater that non-users in

ave 3.5 years.

Continued pot use risk of future psychosis

was 31% vs 20% in those who did not

continue use out to approx 8.5 years.

BMJ 2011;342: d738

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Marijuana and Bipolar Illness

166 first-episode bipolar I disorder patients.

Cannabis and alcohol associated with the

first episode of mania

Bipolar Disorder 2008;10:738-741

Sexual Assault/ Victimization

Alcohol and Marijuana predict violence. Kraanen Journal of Substance Abuse Treatment 46 (2014) 532–539

Marijuana-associated partner aggression Moore Clinical Psych Review 28 (2008) 247-274

College Drug Use and Partner ViolenceNabors Journal of Interpersonal Violence 25(6) 1043–1063

Dating Aggression by AdolescentsReyes Journal of Adolescence 37 (2014) 281–289

Marijuana Disinhibition

From: Joe Davis [ ]

Sent: Friday, November 09, 2012 1:36 AM

To: Voth, Eric

Subject: Marijuana

Your views on marijuana are so ignorant

and wrong I feel so sorry for your pathetic

mind learn to accept people's differences

and stop being a judgemental piece of shit

Gateway Effects

&Addiction

Gateway effects

Risk of other drug use with weekly

marijuana vs nonusers:

14-15 y/o 66.7%

17-18y/o 28.5%

20-21y/o 12.2%

24-25y/o 3.9%Fergusson DM, et al.

Addiction 2006;101:556-569

Marijuana Dependence

Most patients claimed serious problems with

cannabis, and 78.6% met criteria for cannabis

dependence.

Two thirds reported withdrawal. Cannabis is a

reinforcer. produces both dependence and

withdrawal and reinforces cannabis use.

Regular cannabis use rapid as tobacco

progression, and more rapid than alcohol CrowleyDrug and Alcohol Dependence 1998;50:27-37

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Marijuana treatment episodes

National increase

1992 92,500

2008 322,000

California increase

1992 7300

2008 35000RAND 2010

Altered State?

Assessing How Marijuana Legalization

in California Could Influence

Marijuana Consumption

Fetal/Newborn Effects

Newborn Effects

Birthweight

Length

Head Circumference

Abnormal Development

Neurological Irritability

Effect on Conception

If men smoked marijuana 11 to 90 times in

their lifetime, there was a 15% decrease in

infant birth weight (P = .03)

more than 90 times, there was a 23%

decrease (P=.01).

Women and men who smoked in the past 15

years, had 12%(P=.04) and 16% (P=.03)

smaller infants, respectively.

Fetal Effects: 14 y/o

524 subjects

Confounding variables controlled

Greatest effect first Trimester >1joint /day

Fetal exposure= 14 y/o Wechsler composite

Poor Intelligence age 6

Attention and Depression age 10 Neurotoxicology and Teratology

Goldschmidt and Day

34 (2012) 161–167

SOCIAL AND MEDICAL

IMPLICATIONS

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CESAR FAXU n i v e r s i t y o f M a r y l a n d , C o l l e g e P a r k

A Weekly FAX from the Center for Substance Abuse Research

January 18, 2010

Vol. 19, Issue 2

U.S. High School Seniors’ Perception of Harm from Regular Marijuana Use Decreasing

1975

1976

1977

1978

1979

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

0%

10%

20%

30%

40%

50%

60%

70%

80%

Perceived Risk of Harm

from Regular Use

Used in Past Month

Percentage of U.S. Twelfth Grade Students Reporting Past Month

Marijuana Use and Perceived Risk of Harm from Regular Marijuana Use, 1975-2009

SOURCE: Adapted by CESAR from University of Michigan, “Teen Marijuana Use Tilts Up, While Some Drugs Decline in Use,” Press Release, 12/14/09. Available online at

http://www.monitoringthefuture.org/data/09data.html#2009data-drugs.

2012-13 National Household Survey

http://data/sites/def

ault/files/NSDUHSt

ateEst2012-2013-

p1/Maps/NSDUHsa

eMaps2013.pdf

Perception of Harm –

% reporting NO RISK with regular use

The Colorado Social Experiment

Marijuana and Fatal Crashes

Colorado Since DispensariesFatal crashes THC Ave Percent THC

2006 21 2.9

2007 23 2.9

2008 31 4.4

2009 37 5.7

2010 42 7

2011 52 8.9

2010Colo Dept of Transportation

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National Survey on Drug Use and Health,

2013 released Jan 2014 SAMHSA

Past-month use in Colorado increased

22% from 10.41 % to 12.7 % between 2012

and 2013, one year after the state legalized

recreational marijuana in November 2012

but one year before recreational pot shops

opened for business in January 2014.

Colorado legalized medical marijuana in

2000 when 7.8 percent of its citizens used

the drug monthly compared to 12.7% in

2013National Survey on Drug Use and Health,

2013 released Jan 2014 SAMHSA

Adult Marijuana Use Colorado

485,000 Colorado adult regular marijuana

users (at least once/mo) = 9% population

Heavy users (daily) = 21.8% of user

population and 66.9% of demand

Colorado near daily users 35.29% higher

than national average

Alcohol consumption unchanged in

Colorado since 2005Rocky Mountain HIDTA, 2014

Child Marijuana Poisonings

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Colorado Dispensaries

493 medical/212 recreational dispensaries

149 medical/63 recreational marijuana infused product

factories

729 medical/279 recreational cultivation operations

0 medical/8 recreational testing facilities

One marijuana store in Denver for every 3,780 residents

“Denver has more marijuana dispensaries than liquor

stores or licensed pharmacies.”

Colorado Department of Revenue, Marijuana Enforcement Division; July 24, 2014

Dr. Christian Thurstone, M.D., attending physician, Denver Health Medical Center

Marijuana and Crime

All reported Denver crime

(compare Jan-June 2013 to Jan-June 2014)

• Person Crime ↑ 18.1%

• Property Crime ↑ 8%

• All Offenses ↑ 114.9%

National Incident Based Reporting System

Colorado Marijuana Interdiction

Seizures

El Paso Intelligence Center, National Seizure System

Marijuana and Crime Nationally

Chance of being arrested = 1 in every

11,000 – 12,000 joints smoked

Less than 1% serving time for simple

possession of marijuana

Median amount of marijuana = 115 pounds

RAND, 2010. Altered State? Assessing How Marijuana Legalization in California Could Influence Marijuana Consumption.

Multiple Sources including Bureau of Justice Statistics & Caulkins and Sevigny (2005)

U.S. Sentencing Commission, 2011.

Poorly Known Facts

The data from legalization is lagging

At least two Denver high schools have

opened on-site treatment programs

Denver homeless drug-tourists

Denver General child poisonings.

Practical Issues/ Regulation

What marijuana will be allowed, what strengths, and who pays for it?

Who produces the marijuana?

Is marijuana purity assured?

Is the caregiver licensed and in good standing with regulatory agencies?

Does the caregiver demonstrate formal training or experience in addiction and in the administration of dangerous drugs?

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Practical Issues/Regulation

Has user exhausted all other accepted

medical interventions?

Is the proposed patient a drug abuser?

Does law allow for drug screening to assure

no use of illegal drugs?

Will patient have medical oversite and

monitoring of status and adverse Events

Legal liability and responsibility?

Responsibilities of Public Health

Safe, effective reliable medicines are best for patients, and they are available

Marijuana is impure, unreliable, full of contaminants, high side effect rate.

Defense to possession bypasses FDA and jeopardizes consumer protection

Medical excuse marijuana creates “medicine by popular vote.”