Study finds genetic overlap between cannabis use and schizophrenia
(Alfredo Gayou / Flickr)
The association between marijuana and schizophrenia is historically fraught. In the 1960s and 1970s, scientists thought that smoking weed could trigger psychosis in just about anyone. Today, these findings are more nuanced, but researchers still think that cannabis can trigger schizophrenia in people who are predisposed to the disease — meaning those with family
histories of the disorder. Yet, in the last decade, some scientists
have actually started to look at the effect in reverse. The resulting studies suggest
that the neurobiology underlying schizophrenia might also put people
affected by the disorder at increased risk for smoking pot. But these
results haven't garnered nearly as much attention as studies suggesting
the opposite.
part of the association might be caused by genetic overlap
Now, a new study, published today in Molecular Psychiatry,
lends further support to the idea that schizophrenia plays a role in an
individual's likelihood of smoking weed, by showing that the genetic
variants predicting schizophrenia can also be used to predict a person's
tendency to smoke pot, regardless of their mental health history. This, researchers say, demonstrates that the causal relationship between cannabis use and schizophrenia
might not be clear-cut, and that at least a small part of the
association might be caused by genetic overlap, where the same genes
that predispose certain people to enjoying weed might also predispose
others to developing schizophrenia — or both.
To tease apart this
relationship, researchers took genetic data from recently published
studies of schizophrenia, and identified genetic variants associated
with the disease. Then, they applied
that information to a random sample of about 2,000 healthy Australians
to see if those variants could also predict cannabis use.
"more likely to use cannabis, and in greater quantities."
"There is a well-established link between people who use cannabis and schizophrenia," says Robert Power, lead author of the study
and a genetic psychiatrist at King's College London. But this study
indicates "that people who are at risk for schizophrenia are more likely
to use cannabis, and in greater quantities," he says — which means the
causal relationship might actually go both ways.
Moreover, the genetic
variants associated with schizophrenia were predictive for cannabis use
in healthy individuals, so there appears to be some genetic overlap
between the two.
"These findings are
very valuable," says Eden Evins, a psychiatry professor at Harvard
University who was not involved in the study, "and suggest that
increased genetic risk for schizophrenia
increases the chance that someone will use cannabis, and use it
heavily." But Evins doesn't think these results rule out previous
findings that cannabis use increases a person's risk for developing
schizophrenia. "Both may be true," she says.
This sentiment was echoed
by Wolfram Kawohl, a psychiatrist at the University of Zurich, who said
the results show that "the connection is more complicated than some
people may have thought," and that "both connections may exist parallel
along with possible others."
"I am suspect that this finding will hold out with the test of time."
But Lynn DeLisi, another Harvard University psychiatry professor, isn't convinced. "I am suspect that this finding will hold out with the test of time," she told The Verge in an email.
DeLisi points to her own work, which showed there was no difference in family history
of schizophrenia between people who smoke weed and people who don't.
So, although there might be an interaction between smoking weed and
schizophrenia, DeLisi said, it would be need to be shown in "studies of
people using cannabis compared with those who don't, both having a
family history of schizophrenia."
Furthermore, DeLisi thinks that today's high rates of cannabis use among teenagers and adults make it hard to link drug use to mental health issues
or their genetic predispositions. "Everyone uses cannabis these days,
and I don't think they necessarily have genetic predispositions to do
so."
An ongoing debate
"The relationship is an ongoing debate in the scientific world — at least what the nature of the association is," said Matthew Hill, a cell biologist at the University of Calgary in Canada, who recently published an article dissecting this very relationship, in an email to The Verge.
In the article, Hill argued that "there is little evidence that, at a
population level, cannabis use during adolescence is a primary
contributing factor in the development of psychiatric illness." But he
also noted that "there is evidence that in high-risk populations,
cannabis can be highly adverse, so arguments claiming that cannabis is innocuous are equally flawed."
Weed affects people with schizophrenia differently
When The Verge asked
about the risks associated with cannabis use, Hill said that "there are
detailed studies which have demonstrated that cannabis can have very
different effects on the brain of someone who is at risk for schizophrenia than someone who isn't." One 2013 study, for instance, demonstrated that the increased release of dopamine from smoking marijuana is
amplified in the brains of people with schizophrenia, as well as in
their close relatives. The results of this amplification are poorly
understood, but some scientists think that a chronic elevation of
dopamine can increase one's likelihood of experiencing psychotic
episodes, and make the disorder harder to treat.
Moreover, some studies
indicate that people who find themselves in the early stages of
schizophrenia and who also smoke weed experience larger brain
modifications — such as changes in their white matter — compared to
those who don't.
"cannabis use worsens the course of schizophrenia."
"There is definitely some kind
of genetic basis to increased vulnerability to these adverse effects
[in people with schizophrenia] that go beyond the correlational
association discussed in this paper," Hill says.
Evins agreed.
"It's well known that cannabis use worsens the course of
schizophrenia," she said, "so people with schizophrenia should be
discouraged from using it."
Furthermore, some
studies have found that smoking pot accelerates the development of
schizophrenia in those who are genetically predisposed, but that
association took a hit in 2010, when researchers found that accounting for things like gender, lifetime mental health history, and socioeconomic status erased the effect. Still, some studies continue to point to this risk.
Perhaps the reasons
for these contradictory findings is that some individuals with
schizophrenia react more strongly to marijuana than others with the same
disorder. This was the finding of one 2010 study
that demonstrated that 44 out of 121 schizophrenic participants either
developed schizophrenia within a month of beginning to smoke marijuana,
or saw their psychosis amplified by drug use.
A complicated relationship
Given all of this
conflicting evidence, it seems likely that the relationship between
marijuana and schizophrenia is even more complex than we once thought.
No single gene has been associated with either drug addiction
or schizophrenia, so these illnesses are the result of many genes
working in combination, Evins said, "each with a small contribution to
the overall risk of developing the disorders." There's also a plethora
of environmental factors that need to be taken into account — most of
which we barely understand.
This "doesn't get a lot of attention."
Still, Hill said, the idea that cannabis use and schizophrenia
share common genes "is interesting," partly because it highlights a
dimension of this relationship that doesn't get a lot of attention. But
causality is never easy to confirm, so this study will need to be
replicated multiple times. And even then, Kawohl said, researchers
probably won't be able to say that "cannabis use has no consequences for
the risk to develop schizophrenia."
Regardless, it's important to remember that schizophrenia only affects a small number of people — about 1 percent
of the US adult population — so "the vast majority of adolescents and
young adults who use cannabis won't develop it," Evins said. And that's
actually a crucial point, because despite all the studies that link
schizophrenia and cannabis, few have been able to explain why
schizophrenia rates have remained stable — and may actually be declining — in the face of pot's increasing popularity among teens.
the economic benefit of limiting pot use is "pretty small."
"There may still be a
causal role between cannabis and schizophrenia, but our results suggest
that this causal role may have been overestimated," Power says. This is
important, he says, because some people have used cannabis'
relationship with psychosis to argue against its legalization. "Already
the actual economic benefit of limiting cannabis use in terms of schizophrenia is pretty small," Power says, pointing to a study that found that policymakers would have to stop at least 3,000 adolescents from smoking weed to prevent one case of psychosis from emerging.
Still, Power thinks people with a family history
of schizophrenia should avoid weed. "The clinical advice is to stay
away from events that might have a potential to cause stress," he says,
because genes and environment are interconnected. Thus, "people who are
at-risk should try to avoid things that might damage their mental
well-being." These things, he says, include weed.
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