The link between weed and schizophrenia is way more complicated than we thought

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.