“Medical” marijuana is approved in 21 states and the
District of Columbia for numerous conditions, including
glaucoma, Crohn disease, posttraumatic stress disorder,
epilepsy, Alzheimer disease, and chemotherapy-induced
nausea and vomiting. Both the number of states and
the number of approved indications for medical
marijuana are expected to increase. Physicians will
bear the responsibility of prescribing marijuana and
thus have an obligation to understand the issues
involved in its “medicalization.”
Medical marijuana differs significantly from other
prescription medications. Evidence supporting its
efficacy varies substantially and in general falls short of
the standards required for approval of other drugs by
the US Food and Drug Administration (FDA). Some
evidence suggests that marijuana may have efficacy in
chemotherapy-induced vomiting, cachexia in HIV/AIDS
patients, spasticity associated with multiple sclerosis,
and neuropathic pain. However, the evidence for use in
other conditions—including posttraumatic stress
disorder, glaucoma, Crohn disease, and Alzheimer
disease—relies largely on testimonials instead of
adequately powered, double-blind, placebo-controlled
randomized clinical trials. For most of these conditions,
medications that have been subjected to the rigorous
approval process of the FDA already exist. Furthermore,
the many conditions for which medical marijuana is
approved have no common etiology, pathophysiology,
or phenomenology, raising skepticism about a common
mechanism of action.
There is no clear optimal dose of marijuana for its
various approved conditions. The concentration of Δ -
tetrahydrocannabinol (THC) and other cannabinoids in
each marijuana cigarette, the size of cigarettes, and the
quantity of smoke inhaled by users can vary
considerably. The relative lack of controlled clinical trial
data makes finding the appropriate dose even more
challenging. Furthermore, given that medical marijuana
is approved for mostly chronic conditions that require
long-term dosing, physicians must be aware of the
development of tolerance and dependence (as
evidenced by downregulation of the brain cannabinoid
receptors), as well as withdrawal on discontinuation.
Prescription drugs are produced according to exacting
standards to ensure uniformity and purity of active
constituents and excipients. Because regulatory
standards of the production process vary by state, the
composition, purity, and concentration of the active
constituents of marijuana are also likely to vary. This is
especially problematic because unlike most other
prescription medications that are single active
compounds, marijuana contains more than 100
cannabinoids, terpenoids, and flavonoids that produce
individual, interactive, and entourage effects. Although
THC is believed to be the principal psychoactive
constituent of marijuana, other cannabinoids present in
marijuana may have important effects that may offset
THC’s negative effects. For instance, cannabidiol has
been shown to have anxiolytic and antipsychotic effects
that might offset the anxiogenic and psychotogenic
potential of THC. Yet cannabidiol is sometimes bred
out to increase the THC potency of some medical
marijuana strains.
Benefits notwithstanding, the potential harms
associated with medical marijuana need to be carefully
considered. No other prescription medication is
smoked; concerns remain about the long-term risks of
respiratory problems associated with smoking
marijuana, which are a subject of active investigation.
THC is already available in a pill approved by the FDA,
yet this form seems to be less desirable to those
seeking medical marijuana; this may in part be because
its euphoric effects are not immediate and cannot be
reliably controlled, unlike smoked marijuana.
Furthermore, there is evidence that marijuana exposure
is associated with an increased risk of psychotic
disorders in vulnerable individuals. Clearly, some but
not all individuals are at risk of psychosis with
exposure to marijuana, but it is not possible to identify
at-risk individuals. In individuals with established
psychotic disorders, marijuana use has a negative effect
on the course and expression of the illness.
Furthermore, recent findings suggest that long-term
marijuana exposure is associated with structural brain
changes as well as a decline in IQ.
The current system of dispensing marijuana does not
safeguard adequately against the potential for diversion
and abuse. Many states, for instance, allow patients to
grow their own marijuana. Furthermore, marijuana may
be contaminated with pesticides, herbicides, or fungi,
the latter being especially dangerous to
immunocompromised individuals such as patients with
HIV/AIDS or cancer. Central regulatory oversight by
the FDA makes possible the recall of harmful drugs or
contaminated batches and the dissemination of new
information about drug safety. Is there sufficient
oversight to monitor potential contamination of
marijuana, especially when patients are permitted to
grow it themselves?
A significant but largely overlooked problem with the
medical marijuana movement is the message the public
infers from its legalization and increasing prevalence.
There is an increasing perception, paralleling trends in
legalization, that marijuana is not associated with
significant or lasting harm; data from 3 decades
indicate that among adolescents, risk perception is
inversely proportional to prevalence of cannabis use.
As legalization has spread for medical or recreational
purposes, it is possible that the perception of risk by
adolescents will continue to decrease, with a
subsequent increase in use. This is especially
problematic given that many of the negative effects of
marijuana are most pronounced in adolescents.
Projections of substantial revenue rather than evidence-
based medicine may explain the eagerness of many
states to legalize medical marijuana. Physicians have
been invited to participate in the development of
medical marijuana programs late in the process. In
some instances (eg, Connecticut), legislators approved
medical marijuana but consulted physicians with
relevant expertise only afterward.
An unmet need remains for treatments of a number of
debilitating medical conditions. Specific constituents of
marijuana may have therapeutic promise for specific
symptoms associated with these disorders. However, if
marijuana is to be used for medical purposes, it should
be subjected to the same evidence-based review and
regulatory oversight as other medications prescribed by
physicians. Potentially therapeutic compounds of
marijuana should be purified and tested in randomized,
double-blind, placebo- and active-controlled clinical
trials. Toward this end, the federal government should
actively support research examining marijuana’s
potentially therapeutic compounds. These compounds
should be approved by the FDA (not by popular vote or
state legislature), produced according to good
manufacturing practice standards, distributed by
regulated pharmacies, and dispensed via a conventional
and safe route of administration (such as oral pills or
inhaled vaporization). Otherwise, states are essentially
legalizing recreational marijuana but forcing physicians
to act as gatekeepers for those who wish to obtain it.
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