Studies link psychosis,
teenage marijuana use
carry genetic risk
By Carey Goldberg, Boston Globe Staff |
January 26, 2006
Researchers are offering new ammunition to worried parents
trying to dissuade their teens from smoking marijuana:
Evidence is mounting that for some adolescents whose genes
put them at added risk, heavy marijuana use could increase
the chances of developing severe mental illness -- psychosis
This week, the
marijuana-psychosis link gained ground when two major
medical journals reviewed the research to date and concluded
that it was persuasive. In PLOS Medicine, an Australian
public health policy specialist wrote that genetically
vulnerable teens who smoke marijuana more than once a week
''appear at greater risk of psychosis," while the British
medical journal BMJ cited estimates that marijuana use could
contribute to about 10 percent of cases of psychosis.
The new research has little
hint of ''Reefer Madness" alarmism. Rather, a half-dozen
long, careful studies published in the last several years
have tried to determine whether marijuana-smoking is a cause
rather than an effect of mental illness. And groundbreaking
research has begun to try to pinpoint which genes and brain
chemicals could do the damage.
The conclusions remain
controversial, in part because it would be unethical to
randomly assign teens to smoke or not smoke marijuana --
which would be necessary to perform a gold-standard study to
definitively show that adolescent marijuana use causes
mental illness. It could be the other way around, or some
other factor could put teens at risk of both.
But the recent research has
attempted to get around these hurdles by controlling for
factors such as the presence of psychosis before the use of
marijuana, family income, education, other drug use, and
''No single study is
perfect," Wayne Hall, author of the PLOS Medicine essay and
a professor at the University of Queensland, said in an
e-mail interview. ''But the fact that so many individually
imperfect studies so consistently find this relationship
adds confidence to the conclusion that the relationship is
The recent research points to
adolescence as a particularly risky time to smoke marijuana
heavily for those genetically predisposed to mental illness.
Brain scientists theorize that marijuana may induce
temporary changes in brain chemistry that, when reinforced
over time, become permanent.
Among the research cited
by both papers appearing this week was an intriguing study
published last year that followed a group of more than 800
New Zealanders from birth until age 26. The study looked at
people with a gene variant that apparently predisposes them
to developing psychosis, and people without it. The variant
was carried by 25 percent of the study's participants.
The study found that among
those with this variant, smoking marijuana as teens
increased their risk of psychosis in young adulthood nearly
tenfold compared with those who did not smoke as teens.
Those who smoked marijuana but did not have the gene variant
incurred little or no added risk.
No test of such gene variants
is widely available. Dr. Robin Murray, a psychiatry
professor at Kings College London and an author of the New
Zealand paper, said he and other researchers like to joke
that they should set up a DNA-test tent at rock concerts and
tell customers whether it is safe to get stoned. In reality,
however, the gene research is at too early and tentative a
stage to justify offering a test, he said.
Other studies cited in the
BMJ article found that teens and young adults who smoked
marijuana had roughly double the risk of later developing
psychotic symptoms, but these studies did not distinguish
between carriers and noncarriers of the gene variant.
Still, even among marijuana
smokers, the absolute risk of developing schizophrenia was
low, Murray said -- about 2 percent. And the added risk from
smoking marijuana was small compared to, say, cigarette
smoking, which multiplies a person's chances of lung cancer
by 15, he noted.
affects about one in every 100 people, and two more in every
100 experience a lesser form of psychosis.
This week's PLOS Medicine
essay suggests that teens should be considered vulnerable if
they have psychosis in the family, an indication their genes
may predispose them to it, or have had ''unusual
psychological experiences after using cannabis."
In recent months, the White
House has emphasized a causal link between marijuana and
schizophrenia as part of an antimarijuana campaign, but the
National Institute on Drug Abuse does not list psychosis as
a marijuana risk on its informational website.
The evidence for a link is
becoming more convincing, said Dr. Wilson Compton, who
directs the institute's public health research program. But
he said the agency wants ''to make sure we don't overblow"
the risk, because that would make teenagers likelier to
discount the warnings.
The controversy stems in part
from the challenges of the research. Consider a boy who has
shown early signs of schizophrenia since childhood, lacking
friends and seeking isolation. In his early teens, he starts
hanging out with marijuana-smokers, gets increasingly
withdrawn, and is finally diagnosed with schizophrenia at
In a case like that, it is
likely that the early symptoms of the disease led to the
marijuana-smoking rather than vice versa, said Dr. Harrison
Pope, director of the Biological Psychiatry Laboratory at
Harvard's McLean Hospital.
''I'm not saying the studies
are wrong," he said. ''I'm saying this is a caveat you have
to bear in mind even when you see six studies all in
agreement -- it's very, very difficult in retrospect to
tease apart the chain of causality."
But even marijuana advocates
allow that there could be a link, at least for a small
minority of marijuana smokers.
Marijuana has an excellent safety record when used in
moderation by adults, emphasized
Paul Armentano, senior policy analyst for the National
Organization for the Reform of Marijuana Laws. But ''I would
not rule out that heavy use of marijuana at a young age,
particularly combined with other drugs, could precede onset
of some symptoms of mental illness."
The New Zealand study,
published last year in the journal Biological Psychiatry,
looked at a gene called COMT, which is involved in the
breakdown of dopamine, a chemical known to play a role in
Though the researchers found
a dramatically higher risk when teenagers with the wrong
variant of the gene regularly smoked marijuana, they
cautioned that even so, that combination accounted for only
one-fifth of the people in the study who became psychotic.
''People who smoke pot don't
[automatically] go on to become schizophrenic -- boom boom
boom," said Alan Budney, a professor and federally funded
addiction researcher at the University of Arkansas for
Medical Sciences. ''There's an intricate level of risk
factors that don't apply to Tom, Dick, and Harry -- it just
applies to, say, Jim."
At least, said Murray of
London, he now has better answers for schizophrenic patients
who ask, ''Why is it you're telling me that cannabis
contributed to my going psychotic when all my mates smoked
more than me and nothing ever happened to them?"
Carey Goldberg can be reached