Cannabis and tobacco co-use may significantly increase the risk of psychosis in people already considered clinically high risk, according to a new multisite study in Nature Mental Health. The findings highlight a growing but understudied pattern of substance use and point to the need for closer screening and targeted prevention.
The study found that regular use of either cannabis or tobacco was linked to anxiety, depression and early psychotic experiences.
A new multisite study published in Nature Mental Health found that using cannabis and tobacco together increases the risk of developing psychotic disorders like schizophrenia among those considered high risk.
Researchers led by Heather Ward, MD, assistant professor of Psychiatry and Behavioral Sciences and director of Neuromodulation Research at Vanderbilt Health, analyzed data from more than 1,000 participants in the North American Prodrome Longitudinal Study, which tracks individuals at “clinical high risk” for psychosis. These individuals often experience mild or early symptoms but have not yet developed a full psychotic disorder.
People with psychosis are much more likely to use cannabis and tobacco than the general population.
Heather Ward, MD
“The prevalence of cannabis and tobacco use, known as ‘co-use,’ has been rising in the general population for the past several decades, while exclusive tobacco use has declined and exclusive cannabis use has been on the rise,” Ward said. “However, little is known about cannabis and tobacco co-use in adolescents at risk for psychosis.”
Substance use patterns — tobacco only, cannabis only, co-use, other substances and no substance use — were assessed over a two-year period in 734 individuals at clinical high risk for psychosis and 278 healthy controls.
“Because of their heavy cannabis and tobacco use, people with psychosis are also disproportionately affected by the negative consequences of cannabis and tobacco use,” said Ward, who recently presented study findings at the Society of Biological Psychiatry Annual Meeting in an oral session titled, “High Stakes: Consequences of Cannabis Use in Vulnerable Populations.”
According to Ward, in people with psychosis, tobacco use is associated with a 20-year decreased life expectancy compared to the general population, that is attributable to the medical consequences of tobacco use, such as cardiovascular disease, heart attack, stroke and lung cancer.
“In people in their first episode of psychosis, it is estimated that 25%-50% use cannabis. Cannabis use is associated with more severe psychosis symptoms, poor response to treatment and psychiatric hospitalizations. There is even evidence that cannabis use may cause psychosis in people who are already at risk,” Ward said.
“Tobacco and cannabis use in isolation have devastating consequences for people with psychosis, so we wanted to see if people who co-use cannabis and tobacco had more severe psychiatric symptoms and if they were at greater risk for developing psychosis in the first place.”
The study found that regular use of either cannabis or tobacco was linked to anxiety, depression and early psychotic experiences. However, people who used cannabis and tobacco together did not show worse short-term symptoms than those using just one.
The biggest difference appeared over time. Those who used cannabis heavily and tobacco lightly were almost three times more likely to develop psychosis compared to those who used neither substance.
The results highlight concern about co-use, a growing trend that has been understudied until now. Researchers defined co-use in the study as “using substances at the same time, on the same occasion, or within a defined time frame where their effects may overlap.”
“We found that cannabis and tobacco co-use was associated with a nearly threefold increased risk of developing psychosis in people who were already at risk,” Ward said. “There is evidence to suggest that using tobacco and cannabis together may have synergistic effects on the brain.
“Smoking tobacco and cannabis together increases absorption of THC, the psychoactive component of cannabis. It is possible that co-use itself is contributing to the development of psychosis. However, it is also possible that the people who are going to develop psychosis anyway have an underlying predisposition to using both cannabis and tobacco.”
Ward said it is important for both patients and clinicians to know that cannabis and tobacco co-use is a risk factor for psychosis. Stopping use of cannabis and tobacco may improve mental health symptoms, and it is possible that stopping cannabis and tobacco co-use could reduce risk of developing psychosis in the first place.
The next step is to replicate this finding in other groups of people at risk for psychosis, and “we need to test if stopping cannabis and tobacco use reduces risk of developing a psychotic disorder,” Ward said.
Date: 08.12.2025
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Original Article: Cannabis and tobacco co-use predicts psychosis in clinical high risk cohorts; Nature Mental Health; DOI:10.1038/s44220-026-00648-y