Heavy cannabis use linked to schizophrenia especially among young men

The French psychiatrist Jacques-Joseph Moreau published a book called Hashish and Mental Illness in 1845, the same year that Scientific American brought out its first issue. In it, he explored his own experiences with the drug cannabis at the Paris-based Club des Hachichins—some of which took place alongside the likes of Victor Hugo, Honoré de Balzac and Charles Baudelaire. Two years earlier Moreau described the “undescribable delights” of a “marvelous substance.” But in his 1845 book, he noted in great clinical detail the similarities to psychosis when ingesting high doses.

Nearly two centuries later the possible link between cannabis use and schizophrenia continues to be intensively researched, often provoking heated debate in its wake. A study published on May 4 in the journal Psychological Medicine provides new evidence that problematic cannabis use may lead to schizophrenia, particularly for young men who are heavy users.

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The research, likely the largest epidemiological investigation conducted to date that directly focused on the cannabis-psychosis question, delved into Danish health histories from 1972 to 2021. The study examined health records of 6.9 million people and found that up to 30 percent of schizophrenia diagnoses—about 3,000 in total—could have been prevented if men from 21 to 30 years old had not developed cannabis use disorder. The comparable prevention percentages for the broader age range of 16 to 49 were 15 percent for men and 4 percent for women.

The Danish epidemiology study does not offer hard-and-fast proof of the cannabis-schizophrenia connection, which could be accomplished only through randomized controlled trials. But this link is supported by the fact that marijuana use and potency have risen markedly—from 13 percent THC content in Denmark in 2006 to 30 percent in 2016—alongside a rising rate in schizophrenia diagnoses. “While this isn’t proving causality, it’s showing that the numbers behave exactly the way they should, under the assumption of causality, says Carsten Hjorthøj, the study’s lead author and an associate professor at the Mental Health Services in the Capital Region of Denmark and the University of Copenhagen.

The researchers’ plunge into a nation’s health statistics probed gender and age risks. “We found that the proportion of cases of schizophrenia that were attributable to cannabis use disorder, and those that might have been prevented, was much higher in males than females and, in particular, younger males in whom the brain is still maturing,” Hjorthøj says. “And we saw that this increase was taking place over time, completely in parallel with the increasing potency of cannabis.”

The size of the study might amplify its impact. “This is the first time we’ve seen a large-scale study across an entire population that addresses the relationship of cannabis and schizophrenia across different age and sex groups,” says Wilson M. Compton, deputy director of the National Institute on Drug Abuse (NIDA), which collaborated with the Mental Health Services in the Capital Region of Denmark to design the study. NIDA officials proposed the age and gender analysis after coming across earlier work by the Danish hospital exploring the connection between cannabis and schizophrenia.

The Danish-funded study, Compton says, raises a number of questions for future research as to whether adolescent male brains are more at risk than female brains for developing psychosis from marijuana or whether men’s levels of exposure to cannabis can explain the difference.

The study also has implications for public prevention and treatment strategies. “People are their own agents,” Hjorthøj says. “They can decide for themselves. But they should, if they do use cannabis, decide based on proper data and not from a story that cannabis is completely harmless and maybe even something everybody should use, which I think is the way the public discourse is moving.”

This latest research will likely fail to alter the long-running debate surrounding cannabis, schizophrenia and statistical cause-and-effect relationships. Other researchers—Carl Hart of Columbia University and Charles Ksir of the University of Wyoming—have previously suggested an alternative explanation for the link. In a 2016 review paper, they argued that heavy cannabis use is one among a set of problem behaviors that turns up in some young people who may be vulnerable to schizophrenia. Such young people may use not only lots of cannabis but also cigarettes, alcohol and other drugs, while also neglecting schoolwork, all behaviors that, in sum, might contribute to a higher risk of being diagnosed with psychosis or another mental disorder. “Future research studies that ‘put on blinders’ and focus exclusively on the cannabis-psychosis association will therefore not be of much value to us in our efforts to better understand psychosis and how and why it occurs,” the authors wrote.

David Nutt, a professor of neuropsychopharmacology at Imperial College London and a founder of the nonprofit Drug Science, which provides information about drugs “free from political or commercial influence,” calls the Danish study “intriguing.” But, he adds, “it also raises many more questions.”

Specifically Nutt asks whether some of the cases in the study may have been misdiagnosed with schizophrenia—rather than an alternative diagnosis of another condition, cannabis-induced psychosis. He wonders whether lower reported risk figures for women suggest that cannabis may be protective against schizophrenia. He also points to factors acknowledged by the researchers that could possibly confound results, such as the lack of data on the participants’ frequency of cannabis use or age at first use or on the amount of THC, the psychoactive ingredient in cannabis, in the products they used.

The debate will undoubtedly continue. NIDA’s Compton suggests that prevention and educational programs that warn about cannabis risk may be a way to test whether the purported cannabis-schizophrenia link has some merit. “Scientifically, if you can successfully change the rates of cannabis use, that will test the theory that cannabis causes schizophrenia,” he says. “And so one would assume, if you reduce cannabis use, that the rates would go down.”

Robin Murray, a professor of psychiatric research at the Institute of Psychiatry, King’s College London and co-editor in chief of Psychological Medicine, acknowledges that studies linking problematic cannabis use to schizophrenia have been criticized for being correlational. But the Danish study, he says, examines more closely than previous efforts specific factors—gender and age—involved in the possible link between the drug and the illness. It adds to the growing body of research that has gradually discounted alternatives to cannabis as a trigger for schizophrenia, making this connection increasingly plausible. “So causal effect is almost certain,” Murray says.

“It is currently impossible to prove a 100 percent, definite causal link between any environmental factor and schizophrenia,” he adds, “because we do not have an animal model of schizophrenia.”

“Epidemiology showed a relationship between tobacco smoking and cancer. The proof came from showing that painting tobacco tar on the skin of mice produced tumors,” Murray says. “Unfortunately, we don’t know what we would have to induce in a rodent to prove that cannabis could cause schizophrenia.”