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Medical Marijuana
Martin P. Eason MD, JD
Associate Chief of Staff for Education
Mountain Home VA Medical Center
Controversies in Pain Management Conference
Johnson City , TN
November 13, 2015
Disclosure
•  I have no financial interest in the
presentation or the products discussed
therein
Cannabis
Cannabis flower
A little history…
Chinese Pharmacopoeia of
Emperor Shen Nung circa 2700
BC
•  WB Shaughnessy
•  Used as an analgesic,
sedative, antiinflammatory,
antispasmodic, and
anti-convulsant.
“…producing as sometimes a heavy, lazy state of
agreeable reverie, from which the individual may be
easily roused to discharge any simple duty – sometimes
in a cheerful active of inebriation causing him to dance,
sing and laugh, provoking the venereal appetite, and
increasing the desire for food – and sometimes a
quarrelsome drunkenness, leading to acts of violence”
Christison, R. A Dispensary and Commentary on the Pharmacopoeais of
Great Britain, 1848
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Pure Food and Drug Act – 1906
Harrison Narcotics Tax Act – 1914
Marihuana Tax Act – 1937
Narcotics Control Act – 1956
Comprehensive Drug Abuse Prevention
and Control Act - 1970
Why are mores changing?
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Tax revenue
Job creation
Burden of criminalization
Increasing public support (2012 12% of
Americans used MJ)
Endocannabinoid System
•  Endogenous cannabinoids - principle
molecule is anandamide
•  Two principle receptors: CB1 and CB2
•  Discovered in 1988 and 1993
•  Found throughout the body
Endocannabinoids
CB2 activity
Mechanism of Action
Putative mechanisms in
analgesia
•  Modulator of rostral ventromedial medulla
neuronal activity
•  Anti-nociception effect in descending pain
pathways
•  Anti-inflammatory effects through
decreased prostaglandin production
Phytocannabinoids
•  Over 80 cannabinoids in
cannabis
•  Two most common
substances are THC and
Cannabidiol (CBD)
•  THC agonist for CB1 and
CB2
•  THC most psychotropic of
cannabinoids
•  CBD no psychotropic
properties and does not
work via receptor
Cannabidiol
Tetrahydrocannabinol
THC
•  Smoked, vaporized,
oil extract,
submucosal spray,
eaten
•  Variable
concentrations
(strains, preparations)
•  Psychotropic
properties
•  Unlawful in most
states
Pharmacokinetics
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Terminal ½ life is approximately 30 hrs.
Highly lipophilic
Vaporization becoming more popular
Smoked bioavailability is between 0.1
and .25%
•  Oral bioavailability is b/w 5 and 20%
•  Inhaled levels similar to IV
•  Metabolized by several enzyme systems
(cytochrome P450)
THC – Clinical effects
•  Euphoria, intoxication
•  Inc. HR, dec. alertness, motor stability, sedation
•  Decreased processing speed, attention,
learning, recall; altered perception of time and
velocity
•  Anxiety, panic attack, paranoia, dysphoria,
depressed mood, and possible latent risk of
psychosis in adolescents
•  Tolerance can develop in as little 4 days of use
•  Effects last longer than serum levels
Long term use
•  No evidence of increased lung disease (if
cig use is accounted for)
•  No increased lung or GI cancers
•  Possibility increase in MI incidence in pts.
with CV disease
•  No neurocognitive dysfunction with long
term use
Abstinence syndrome
•  After continuous use of 5-21 days
•  Begins after 12 hours, decreases after 24,
and terminates by 48 -72 hours
•  Anxiety, irritability, insomnia, abdominal
pain, and decreased appetite
Cannabidiol
•  Low affinity for CB1 and CB2
•  No psychotropic activity
•  Increases activity of CB
receptors via a variety of
mechanisms
•  Not FDA approved
•  Has shown effectiveness for
analgesia, neuroprotection,
anti-epileptic
•  Used in mixture of THC and
CBD (nabiximols, Sativex)
Cannabinoid preparations
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Cannabis
Cannibidiol (hemp oil,not FDA approved)
Dronabinol
Nabilone
Nabiximols (THC and CBD, Sativex)
Oral Cannabis extract (OCE)
Ribonabant (CB1 antagonist) – no longer
approved
Dronabinol (Marinol)
•  Synthetic THC
•  Approved for HIV
associated anorexia
and chemotherapy N/
V
•  Schedule III
Nabilone (Cesamet)
•  Synthetic derivative of
THC
•  Approved for chemotx
assoc. N/V who failed
conventional tx
•  Schedule II drug
Nabiximols
•  Combination of THC
and CBD in equal
concentrations
•  Approved for use in
Canada, NZ, and
some EU countries for
chemotx N/V
Putative benefits of
Cannabinoids
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Analgesia
Anti-convulsant
Anti-emetic
Anxiolytic
Neuroprotection
Anti-inflammatory
Anti-tumor
The evidence
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JAMA June 2015; Whiting et al.
Meta analysis of high quality RCTs
Efficacy of cannabinoids for 28 databases
Looked at N/V, appetite stimulation,
chronic pain, spasticity from MS, GAD,
sleep disorder, glaucoma, depression
•  79 trials, 6462 participants
Chronic pain
•  28 studies, 2454 patients
•  Drugs studied: nabiximols, smoked THC, nabilone, THC spray,
dronabinol, vaporized THC, oral THC
•  Types of pain: neuropathic, cancer, diabetic neuropathic,
fibromyalgia, HIV neuropathy, pain from MS
•  Average number of people reporting >30% reduction was better with
CNB
•  Results for cancer and neuropathic pain were similar
•  Nabiximols associate with greater average reduction in pain
compared to placebo
•  Smoked THC reported greatest beneficial effect
•  Studies generally suggested improvement in pain measures but
most individual studies did not reach statistical difference.
Spasticity
•  No clear difference between CNBs
•  Studies generally suggested CNBs
associated with improvement in spasticity
but most did not reach statistical
significance
Nausea and Vomiting
•  CNBs better than placebos and
comparators but did not reach statistical
significance
•  High risk of bias
•  Low quality evidence
Anxiety
•  One study with high risk of bias
•  Greater improvement in anxiety analog
mood scale versus placebo on simulated
speaking test
Adverse effects
•  Asthenia, balance problems, confusion,
dizziness, dry mouth, fatigue,
hallucinations, nausea, somnolence,
nausea
Weaknesses in the trials
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Failure to handle withdrawals
Selective outcome reporting
Inadequate description of randomization
Difficulty with blinding
Conclusion
•  Moderate quality evidence that CNBs are
effective in treating neuropathic pain and
spasticity
•  Low quality evidence that CNBs effective
in treating chemotx N/V and sleep
disorders
•  Very low quality evidence that CNBs
effective in treating anxiety
Review
•  Lynch et al., British Journal of Clinical
Pharmacology, 2011
•  18 trials, 766 participants
•  Effective treatment of neuropathic pain
with cannabis, oromucosal THC extract,
nabilone, and dronabinol
Review
•  American Academy of Neurology systemic
review
•  Pain: cannabis extract effective, (strong
evidence), THC or nabiximols effective
(moderate evidence), smoked THC
(unclear)
•  Spasm: oral THC effective (strong
evidence), THC and nabiximols effective
(moderate evidence)
So you want to recommend cannabinoids
– things to consider
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Inconsistent concentration of THC in cannabis
Legal liabilities of prescribing
Risk benefit ratio compared to traditional treatment
What is the condition you are treating and will it be
responsive?
Have alternative approaches been tried?
What are potential medical and psychiatric risks
(particularly in elderly patients)?
What is the potential for misuse, abuse, and addiction?
What preparation do you want to use?
What to do?
So here we are…
•  23 states allow medical MJ; 4 states and
DC allow recreational
•  Legalization versus decriminalization
•  No prescription for cannabis (schedule I
remember?); can only recommend.
Medical Marijuana Statutes
•  Process of recommendation (may be oral or
written
•  Conditions where MJ can be used (HIV/AIDS,
MS, glaucoma, chronic pain)
•  May require ID card
•  Allows use, growing, and possession up to
certain limits
•  May require dispensaries
Marijuana ID cards
Provider issues
•  Who gets to recommend?
•  How much?
•  What are professional practice guidelines (AAFP
does not endorse MM laws)?
•  What are malpractice issues?
Social issues
•  Who regulates quality? What is quality?
•  Does health department check cookies?
•  How do businesses handle money? Do they pay
taxes?
•  Children in homes of MM users – child
endangerment
•  Drug tests at work and MM use
The future
•  Removal as a scheduled I drug
•  More rigorous studies – particularly with
CBD
•  Should be considered as adjunctive
therapy in multi-modal approach
•  Avenues for research: glucose
metabolism, anti-inflammatory, anti-tumor,
neuroprotection
Thank you!