Summary: A multi-site study reveals that combining cannabis and tobacco, a trend known as “co-use”, significantly increases the long-term risk of developing full psychotic disorders like schizophrenia. The study tracked over 1,000 participants from the North American Prodrome Longitudinal Study, specifically focusing on adolescents and young adults already at “clinical high risk” for psychosis.
The data shows that while isolated or combined use both aggravate short-term psychiatric symptoms, the long-term trajectory differs drastically: individuals heavily using cannabis while concurrently using tobacco face a nearly threefold increased risk of transitioning into a full psychotic disorder.
Key Facts
- A Threefold Risk Surge: Co-use of cannabis and tobacco is associated with a nearly threefold increased risk of developing full-blown psychosis in individuals who already exhibit early or mild clinical warning signs.
- The Synergistic THC Effect: Biologically, smoking tobacco and cannabis together increases the human body’s absorption of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, potentially altering brain chemistry more intensely than cannabis alone.
- Short-Term vs. Long-Term Trajectories: Regular use of either substance independently induces immediate symptoms of anxiety, depression, and early psychotic experiences. However, the devastating impact of combining the two compounds manifests as a delayed, cumulative risk over time rather than worse short-term symptom scores.
- Drastic Mortality Reality: For individuals who have already progressed into full psychosis, ongoing tobacco use is linked to a staggering 20-year decrease in life expectancy due to secondary cardiovascular diseases, heart attacks, strokes, and lung cancer.
Source: Vanderbilt University
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.
“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.
“People with psychosis are much more likely to use cannabis and tobacco than the general population. 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.
Funding: The research was supported by the National Institutes of Health (grants U01MH066134, P50MH066286, U01MH081944, U01MH081902, U01MH081857, R01MH076989, U01MH066069, U01MH081928, U01MH081988, U01MH082022, R01MH116170 and K23DA059690).
Key Questions Answered:
A: It comes down to a biological magnifying glass. Smoking tobacco and cannabis together directly increases the body’s absorption of THC, the main psychoactive component in weed. This joint delivery system can cause synergistic, overlapping effects in the brain, changing neural chemistry far more aggressively than using either substance by itself.
A: These are individuals, often teenagers or young adults—who are currently experiencing mild, early warning signs of psychiatric distress but have not yet developed a full-blown psychotic disorder like schizophrenia. They are highly vulnerable, meaning external triggers like substance co-use can fundamentally push their nervous system over the edge.
A: Quitting both cannabis and tobacco is known to quickly improve day-to-day mental health symptoms like anxiety and depression. Because co-use acts as such a potent long-term catalyst, researchers believe that stopping completely could very well reduce the initial risk of developing a psychotic disorder in the first place.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this psychosis and addiction research news
Author: Craig Boerner
Source: Vanderbilt University
Contact: Craig Boerner – Vanderbilt University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Cannabis and tobacco co-use predicts psychosis in clinical high risk cohorts” by Daniel Bello, Sophia H. Blyth, Rachel A. Rabin, Jean Addington, Carrie E. Bearden, Kristin Cadenhead, Tyrone D. Cannon, Ricardo E. Carrión, Barbara Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, Larry Seidman, William S. Stone, Ming T. Tsuang, Elaine F. Walker, Scott Woods, Roscoe O. Brady Jr & Heather Burrell Ward. Nature Mental Health
DOI:10.1038/s44220-026-00648-y
Abstract
Cannabis and tobacco co-use predicts psychosis in clinical high risk cohorts
Cannabis and tobacco use are highly prevalent among people with psychosis and are associated with medical comorbidities and poor prognosis. Concurrent use of cannabis and tobacco (‘co-use’) is rising in the general population, but has not been studied in psychosis.
Given the devastating consequences of cannabis and tobacco use, it is critical to understand how their co-use affects psychiatric symptoms and the development of psychosis.
Here we used the North American Prodrome Longitudinal Study-2, a multisite prospective study of individuals at clinical high risk for psychosis (CHR), and healthy controls to examine baseline differences in psychiatric symptoms and conversion to psychosis across substance groups: (1) CHR tobacco use, (2) CHR cannabis use, (3) CHR co-use, (4) CHR non-tobacco or cannabis use, (5) CHR without substance use and (6) healthy controls. Among 1,012 participants (734 CHR, 278 controls), more frequent cannabis and tobacco use was linked to greater psychiatric symptom severity.
In survival analyses, heavy cannabis and light tobacco co-use (HR = 2.93, 95% confidence interval (CI) [1.23–6.97], P = 0.015) was associated with higher risk of conversion than no use of either substance. Co-use of tobacco and cannabis was not associated with psychiatric symptom severity but did predict higher risk of conversion to psychosis.
These results highlight the need for strategies that address co-use in CHR populations to mitigate potential long-term psychiatric consequences.
