VOLUME 26 • N UMBER 10 april 2010

Medical marijuana and the mind INSIDE

More is known about the psychiatric risks than the benefits. Autism spectrum

T
he movement to legalize marijuana for
medical use in the United States has
renewed discussion about how this
drug affects the brain, and whether it might
be useful in treating psychiatric disorders.
Unfortunately, most of the research on
marijuana is based on people who smoked
the drug for recreational rather than medi­
cal purposes. A review by researchers in
Canada (where medical marijuana is legal)
identified only 31 studies (23 randomized
controlled trials and eight observational
studies) specifically focused on medical
benefits of the drug.
A separate review by the American Medi­
cal Association (AMA) also concluded that
the research base remains sparse. This was
one reason that the AMA recently urged the
federal government to reconsider its classifi­
cation of marijuana as a Schedule 1 con­
trolled substance (prohibiting both medical
and recreational use), so that researchers
could more easily conduct clinical trials.
Consensus exists that marijuana may
be helpful in treating certain carefully de­
fined medical conditions. In its comprehen­
sive 1999 review, for example, the Institute
of Medicine (IOM) concluded that mari­
juana may be modestly effective for pain
relief (particularly nerve pain), appetite
stimulation for people with AIDS wasting
syndrome, and control of chemotherapy-
related nausea and vomiting.
Given the availability of FDA-approved
medications for these conditions, however,
the IOM advised that marijuana be con­
sidered as a treatment only when patients
don’t get enough relief from currently avail­
able drugs. Additional research since then
has confirmed the IOM’s core findings and
recommendations.
KEY Points
• Medical marijuana may be an option for
treating certain conditions, such as nerve
pain or chemotherapy-related nausea.
• There is not enough evidence to recommend
medical marijuana as a treatment for any
psychiatric disorder.
• The psychiatric risks are well documented,
and include addiction, anxiety, and psychosis.
Although anecdotal reports abound, few
randomized controlled studies support the
use of medical marijuana for psychiatric
conditions. The meager evidence for ben­
efits must be weighed against the much bet­
ter documented risks, particularly for young
people who use marijuana.
Challenges in drug delivery
Marijuana is derived from the hemp plant,
Cannabis. Although marijuana contains
more than 400 chemicals, researchers best
understand the actions of two: THC (delta-
9-tetrahydrocannabinol) and cannabidiol.
THC is the chemical in marijuana pri­
marily responsible for its effects on the
central nervous system. It stimulates can­
nabinoid receptors in the brain, triggering
other chemical reactions that underlie mari­
juana’s psychological and physical effects—
both good and bad.
Less is known about cannabidiol, al­
though the research suggests that it inter­
acts with THC to produce sedation. It may
independently have anti-inflammatory,
neuroprotective, or antipsychotic effects, al­
though the research is too preliminary to be
applied clinically.
Drug delivery remains a major challenge
disorders and the gut
Recommendations for
evaluation and treatment . 4
Options for mild or
moderate depression
Try exercise, psychotherapy,
and relaxation techniques
before medication . . . . . . . 5
Morphine and traumatic
memory
Easing pain early on reduces
risk of post-traumatic stress
disorder . . . . . . . . . . . . . . 6
In brief
Addiction terminology affects
clinicians’ attitudes; Disease-
modifying drug fails in
Alzheimer’s study . . . . . . . 7
Ask the doctor
What tests monitor the meta-
bolic effects of antipsychotics?
What is sensory processing
disorder? . . . . . . . . . . . . . 8
What’s new
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 Medical marijuana continued

for medical marijuana. The FDA has ap­ the dose of the drug and inborn genetic
proved two pills containing synthetic vulnerability.
Editor in Chief Michael Craig Miller, MD
THC. Dronabinol (Marinol) combines Much more is known about the psy­
Editor Ann MacDonald
Founding Editor Lester Grinspoon, MD synthetic THC with sesame oil. Most of chiatric risks of marijuana (whether used
Editorial Board Jonathan F. Borus, MD the active ingredient is metabolized dur­ for recreational or medical purposes)
Christopher B. Daly
Sandra DeJong, MD ing digestion, however, so that only 10% than its benefits.
Frank W. Drislane, MD
Anne K. Fishel, PhD
to 20% of the original dose reaches the Addiction. Observational studies sug­
Donald C. Goff, MD bloodstream. Nabilone (Cesamet) uses a gest that one in nine people who smokes
Stuart Goldman, MD
Alan I. Green, MD
slightly different preparation of synthetic
marijuana regularly becomes dependent
Shelly Greenfield, MD, MPH THC that is absorbed more completely on it. Research both in animals and in
Thomas G. Gutheil, MD
Michael Hirsch, MD into the bloodstream. Among the con­ people provides evidence that marijuana
Matcheri S. Keshavan, MD cerns about both of these drugs, however, is an addictive substance, especially when
Kimberlyn Leary, PhD, ABPP
Robert W. McCarley, MD are that they do not work rapidly, and used for prolonged periods.
Michael J. Mufson, MD the amount of medication that reaches Addiction specialists note with con­
Andrew A. Nierenberg, MD
Scott L. Rauch, MD, PhD the bloodstream varies from person to cern that THC concentration has been
Nadja Lopez Reilly, PhD
Hester H. Schnipper, LICSW, BCD
person. increasing in the herbal form of mari­
Janna M. Smith, LICSW, BCD Another medication under investi­ juana. In the United States, THC concen­
Caroline L. Watts, EdD
Barbara Wolfe, PhD, RN gation in the United States (and already trations in marijuana sold on the street
Editorial Board members are associated with approved for sale in Canada) combines used to range from 1% to 4% of the total
Harvard Medical School and affiliated institutions.
They review all published articles.
THC and cannabidiol. In Canada, it is product; by 2003, average THC concen­
marketed as Sativex. This drug is some­ tration had risen to 7%. Similar trends
Art Director Heather Derocher
Production Editor Nicole Wall times referred to as “liquid cannabis” be­are reported in Europe. This increased
Customer Service cause it is sprayed under the tongue or potency might also accelerate develop­
Phone
E-mail
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elsewhere in the mouth, using a small ment of dependence.
Online www.health.harvard.edu/customer_ service handheld device. However, it takes Less conclusive is the notion that mari­
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More psychiatric risk than benefit duce intense episodes of anxiety.
Harvard Health Publications Part of the reason marijuana works to It is not yet known whether marijuana
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The goal of the Harvard Mental Health Letter is to interpret timely
relieve pain and quell nausea is that, in increases the risk of developing a per­
mental health information. Its contents are not intended to pro-
vide advice for individual problems. Such advice should be offered
some people, it reduces anxiety, im­ sistent anxiety disorder. Observational
only by a person familiar with the detailed circumstances in which
the problem arises. We are interested in comments and suggestions
proves mood, and acts as a sedative. But studies have produced conflicting find­
about the content; unfortunately, we cannot respond to all inquiries. so far the few studies evaluating the use ings. Studies of recreational users suggest
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tory effects in the brain depending on (e.g., that anxious people are more likely

❷ HARVARD MENTAL HEALTH LETTER www.health.harvard.edu april 2010

to use marijuana), a rebound phenom­
enon (e.g., that marijuana smokers feel
worse when withdrawing from the sub­
stance), and other reasons (e.g., genetic
vulnerability).
Mood disorders. Little controlled re­
search has been done about how mari­
juana use affects patients with bipolar
disorder. Many patients with bipolar
disorder use marijuana, and the drug
appears to induce manic episodes and
increases rapid cycling between manic
and depressive moods. But it is not yet
clear whether people who use mari­
juana are at increased risk of develop­
ing bipolar disorder.
The small amount of research avail­
able on depression is also muddied. In
line with what studies report about anx­
iety, many marijuana users describe an
improvement in mood. Animal stud­
ies have suggested that components of
marijuana may have antidepressant ef­
fects. Yet several observational studies
have suggested that daily marijuana use
may, in some users, actually increase
symptoms of depression or promote
the development of this disorder.
For example, an Australian study
that followed the outcomes of 1,601
students found that those who used
marijuana at least once a week at ages
14 or 15 were twice as likely to develop
depression seven years later as those
who never smoked the substance—
even after adjusting for other factors.
Young women who smoked marijuana
daily were five times as likely to de­
velop depression seven years later as
their non-smoking peers. Although
such studies do not prove cause and
effect, the dose-outcomes relationship
is particularly worrisome.
Psychosis. Marijuana exacerbates
psychotic symptoms and worsens out­
comes in patients already diagnosed
with schizophrenia or other psychotic
disorders. Several large observational
studies also strongly suggest that using
marijuana—particularly in the early
teenage years—can increase risk of de­
veloping psychosis.
april 2010 www.health.harvard.edu HARVARD MENTAL HEALTH LETTER ❸
An often-cited study of more than
50,000 young Swedish soldiers, for
example, found that those who had
smoked marijuana at least once were
more than twice as likely to develop
schizophrenia as those who had not
smoked marijuana. The heaviest us­
ers (who said they had used the drug
more than 50 times) were six times as
likely to develop schizophrenia as the
nonsmokers.
Until recently, the consensus view
was that this reflected selection bias:
Individuals who were already vulner­
able to developing psychosis or in the
early stages (the prodrome) might be
more likely to smoke marijuana to quell
voices and disturbing thoughts. But
further analyses of the Swedish study,
and other observational studies, have
found that marijuana use increases the
risk of psychosis, even after adjusting
for possible confounding factors.
Although cause and effect are hard
to prove, evidence is accumulating that
early or heavy marijuana use might
not only trigger psychosis in people
who are already vulnerable, but might
also cause psychosis in some people
who might not otherwise have devel­
oped it.
Certainly genetic profile mediates
the effect of marijuana. People born
with a variation of the gene COMT are
more vulnerable to developing psycho­
sis, for example. Because there is as yet
no reliable way for clinicians to identify
vulnerable young people in advance,
however, it is safest to restrict use of
medical marijuana to adults.
Other effects
A review of side effects caused by med­
ical marijuana found that most were
mild. When compared with controls,
people who used medical marijuana
were more likely to develop pneumonia
and other respiratory problems, and
experience vomiting, and diarrhea.
There’s no question that recreational
use of marijuana produces short-term
problems with thinking, working mem­
ory, and executive function (the ability
to focus and integrate different types of
information). Although little research
exists on medical marijuana, anecdotal
reports indicate that some patients take
the drug at night to avoid these types
of problems.
The real debate is about whether
long-term use of marijuana (either
for medical or recreational purposes)
produces persistent cognitive prob­
lems. Although early studies of recre­
ational users reported such difficulties,
the studies had key design problems.
Typically they compared long-term
marijuana smokers with people who
had never used the drug, for example,
without controlling for baseline char­
acteristics (such as education or cogni­
tive functioning) that might determine
who continues to smoke the drug and
who might be most at risk for thinking
and memory problems later on.
Recent studies suggest that although
overall cognitive ability remains intact,
long-term use of marijuana may cause
subtle but lasting impairments in ex­
ecutive function. There is no consen­
sus, however, about whether this affects
real-world functioning.
Additional research, focused on the
benefits and consequences of medi­
cal marijuana use for specific disor­
ders, may help to clarify some issues.
In the meantime, there is not enough
evidence to recommend marijuana as
a medical treatment for any psychiat­
ric disorder.
Crippa JA, et al. “Cannabis and Anxiety:
A Critical Review of the Evidence,” Human
Psychopharmacology (Oct. 2009): Vol. 24,
No. 7, pp. 515–23.
Grinspoon L, et al. Marijuana: The Forbidden
Medicine (Yale University, 1997).
Iversen LL. The Science of Marijuana, Second
Edition (Oxford University Press, 2008).
Wang T, et al. “Adverse Effects of Medical
Cannabinoids: A Systematic Review,” Cana-
dian Medical Association Journal (June 17,
2008): Vol. 178, No. 13, pp. 1669–78.
For more references, please see
www.health.harvard.edu/mentalextra.
Source: from Harvard Mental Health Letter, Harvard Health Publications, Copyright 2010 by President and
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