Transcript Medical Marijuana: Risks and Benefits

Medical Marijuana: Risks and
Benefits
Malcolm P. Rogers, M.D.
Portland VA Clinic
malcolm. [email protected]
Brief History
• Long History of Use as Herbal Medicine
• 1937: Severely Restricted – Medical Marijuana
Tax Act
• 1970 : Controlled Substances Act – Places
marijuana into Schedule 1
• 1996: California law sanctions medical use of
marijuana and protects patients and providers
from prosecution
History (continued)
• 2005 US Supreme Court (Gonzales v Raich)
overturns California’s law by 6-3 vote
• About a dozen other states allow medical
marijuana
• October 2009: Obama Administration
discourages US Attorneys from taking
enforcement actions in medical marijuana states
• November 2009: Maine votes yes on medical
marijuana dispensaries
Medical Community Response
• February 2009: American College of Physicians
calls for “evidence-based review of
marijuana’s status as Schedule 1 controlled
substance to determine whether” to reclassify
• November 2009: AMA voted to change
classification, affirming therapeutic benefits
for neuropathic pain, improving appetite and
relieving spasticity and pain in MS patients
Biology of Cannabis
• Cannabis is complex: plant contains over 60
cannabinoid molecules and 500 total compounds
• 1964: Active substance in herbal marijuana found
to be delta-9-tetrohydrocannabinol (THC)
• 1990: CB1 & CB2 receptors binding THC &
endocannabinoids soon discovered
• Receptors primarily in frontal regions of cortex
but also in basal ganglia, cerebellum,
hypothalamus , pituitary, anterior cingulate gyrus,
spinal cord and peripheral nervous system
Biology of Cannabis
• CB1 receptors also found in fat and muscle
cells
• CB1 most abundant G protein-coupled
receptor in brain
• THC acts by inhibiting the release of
neurotransmitters: L-glutamate, GABA,
noradrenaline, dopamine, serotonin and
acetylcholine
Potential Therapeutic Role
• Regulation of hunger and weight
• Regulates fat cells, lipids and glucose
• Preventing action of CB1 receptor reduces
nicotine dependence
• Rimonabant trials were not successful and
drug withdrawn from European market
• HPA axis:
– potential effect on stress response, fertility and
sexual response
Benefits - Cancer Chemotherapy
• Tramer et al: BMJ 323: 16, 2001
– 30 randomized comparisons with other
antiemetics, 1336 patients: reduced nausea and
vomiting more than other agents
• Good side effects: high, euphoria, sedation
• Bad side effects: dizziness, dysphoria, paranoia
• Machado-Rocha FC, et. Al: Eur. J. Cancer Care
17:431, 2008
– Systematic review and meta-analyses showed
superiority of cannabis over placebo and
conventional drugs - but more adverse effects
Stimulates Appetite
• Anorexia in chemotherapy treated cancer
patients
• Wasting in HIV/AIDS
– One of the oral preparations dronabinol (Marinol)
is approved for anorexia associated with AIDS
MS and Neuropathic Pain
• MS Spasticity – relieves muscle spasticity and
related pain
• Ghaffar et al. Neurology 71:164, 2008.
• Neuropathic Pain – both central and
peripheral
• Abrams D et al. Neurology 68:515, 2007.
Possible Benefits
• Reduction of anxiety and anger in occasional,
non-medical users
– anecdotal evidence for as well as against in terms
of panic attacks and paranoia
• Arthritis, asthma, migraine, motor tics, ALS,
cerebral palsy, gastrointestinal (Crohn’s),
glaucoma, hepatitis C, neuroprotection and
chronic pain
Adverse Effects – Psychosis Risk
• Systematic review of longitudinal and
population based studies
• 7 studies
• Risk of developing psychosis
– 2.58 times more likely if ever used
– Confounding factors :
• Reverse causation, intoxication
• Suggestion that risk higher if use occurs before age 16
– Moore et al, Lancet 370: 319,2007
Adverse Effects – Psychosis Risk
• Only small percentage of people using
marijuana develop psychosis
• In existing psychosis, marijuana use can
exacerbate symptoms, worsen course, trigger
relapse
• Insufficient alone to cause psychosis but
interacts with other risk factors
– Family hx, neurobehavioral deficits, social
withdrawal
Adverse Effects – Mood & Affect
• Affective dysregulation in adolescents
• Amotivational Syndrome
• Limited support from systematic metaanalyses for increased depression risk
• Anxiety – case reports of panic disorder but
overall data unclear.
Adverse Effects – Cognition and
Memory
• Acute effects on visuo-spatial working
memory
• Impairs executive function in short term
abstinent cannabis users
• Memory problems can persist for one month
after last use but long term effects unclear
• fMRI suggests that neurodevelopment might
be altered in adolescents with persistent
neurocognitive deficits
Other Adverse Effects
• Addictive Potential
• Association with relapse in other substance
abuse, for example, opioid abuse in suboxone
patients
• Risks associated with legal prohibition
• Marijuana smoke and medical risk
Adverse Effects - Medical
• Potential increased risk of cancer and
cardiovascular disease
– Cannabis smoke delivers 50-70% more
carcinogenic hydrocarbons than tobacco smoke
– Higher risk of cardiac arrhythmias
• Oral (Marinol) or sublingual preparations
(Sativa) alternatives but might not be as
effective
Summary
• Benefits:
– nausea and appetite in cancer
– spasticity in MS
– neuropathic pain
• Risks: (mostly in high frequency recreational
users):
– psychosis
– cognitive impairment
– mood and motivation
– medical