Summary: A multisite study shows that using cannabis and tobacco together — commonly called “co-use” — substantially raises the long-term likelihood of developing a full psychotic disorder such as schizophrenia. The research followed more than 1,000 participants from the North American Prodrome Longitudinal Study, focusing on adolescents and young adults who were already classified as being at clinical high risk for psychosis.
While regular use of cannabis or tobacco alone is linked to immediate increases in anxiety, depression and early psychotic symptoms, the combination of the two substances produces a different and more dangerous trajectory: heavy cannabis use combined with even light tobacco use was associated with nearly a threefold greater risk of converting to a diagnosable psychotic disorder over time.
Key Facts
- A threefold increase in conversion risk: Individuals at clinical high risk who engaged in heavy cannabis use together with light tobacco use had almost three times the risk of developing a full psychotic disorder compared with those who used neither substance.
- Synergistic THC effect: Smoking tobacco and cannabis together increases the body’s absorption of delta-9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, producing stronger and potentially more harmful effects on brain chemistry than cannabis alone.
- Different short- and long-term impacts: Either substance on its own is associated with short-term increases in anxiety, depression and subthreshold psychotic experiences. The greatest danger of co-use is its delayed, cumulative effect that elevates long-term risk for conversion to psychosis.
- Serious mortality consequences: Among people who develop psychotic disorders, ongoing tobacco use contributes to substantially reduced life expectancy — on the order of two decades — largely because of cardiovascular disease, heart attacks, stroke and lung cancer.
Source: Vanderbilt University
Overview of the study
Researchers led by Heather Ward, MD, analyzed data from 1,012 participants (734 individuals at clinical high risk for psychosis and 278 healthy controls) enrolled in the North American Prodrome Longitudinal Study. The team evaluated substance-use patterns across five groups over a two-year period: tobacco only, cannabis only, co-use (tobacco and cannabis together), other substance use, and no substance use.
The investigators found that increased frequency of cannabis or tobacco use correlated with greater psychiatric symptom severity at baseline. However, co-use did not necessarily produce worse short-term symptom scores than single-substance use. The most notable finding emerged in survival analyses: heavy cannabis combined with light tobacco co-use significantly predicted conversion to psychosis (hazard ratio 2.93), while neither substance alone produced the same level of long-term risk in this cohort.
Co-use was defined in the study as using substances at the same time, on the same occasion, or within a time frame where their effects overlap. The researchers emphasize that the combination may have interactive effects on the brain. One plausible mechanism is enhanced THC absorption when tobacco and cannabis are smoked together, amplifying psychoactive impact and potentially accelerating processes that lead to psychosis in vulnerable individuals. At the same time, the authors acknowledge an alternative possibility: people who are biologically predisposed to psychosis might also be more likely to use both substances.
Clinical implications
For clinicians and patients, the study underscores the importance of screening for both cannabis and tobacco use among adolescents and young adults showing early psychiatric symptoms. Because quitting either or both substances often improves daily mental health symptoms such as anxiety and depression, cessation interventions might also reduce long-term conversion risk, though causal evidence for prevention requires further study.
The researchers recommend replicating these findings in independent samples of people at clinical high risk and conducting interventional studies to determine whether stopping co-use reduces the likelihood of developing a psychotic disorder.
Funding: This 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: Combining tobacco and cannabis increases the absorption of THC, intensifying its psychoactive effects. This overlap can produce synergistic impacts on neural systems, altering brain chemistry more aggressively than either substance alone and increasing long-term risk in vulnerable people.
A: Clinical high risk describes individuals—commonly adolescents or young adults—who display early, subthreshold signs of psychiatric disturbance (such as brief psychotic-like experiences or marked functional decline) but have not yet developed a full psychotic disorder. These individuals are more vulnerable to environmental triggers that can precipitate conversion.
A: Stopping cannabis and tobacco use is linked to rapid improvements in everyday symptoms like anxiety and depression. Because co-use appears to act as a potent long-term catalyst for conversion, researchers believe cessation could reduce the chance of developing a psychotic disorder, though randomized intervention studies are needed to confirm causality.
Editorial notes
- Article edited and reviewed by a Neuroscience News editor.
- The journal paper was reviewed in full and additional context was added by staff.
About this 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 et al., 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 common among people with psychosis and are linked to poorer health outcomes and prognosis. Concurrent use of both substances is increasing in the general population but has been understudied in relation to psychosis.
Using the North American Prodrome Longitudinal Study-2, a multisite prospective cohort of individuals at clinical high risk for psychosis and healthy controls, this analysis compared baseline psychiatric symptoms and rates of conversion to psychosis across substance-use groups: CHR tobacco use, CHR cannabis use, CHR co-use, CHR other substance use, CHR with no substance use, and healthy controls. Among 1,012 participants, more frequent cannabis and tobacco use correlated with greater psychiatric symptom severity. In survival analyses, heavy cannabis with light tobacco co-use (HR = 2.93, 95% CI [1.23–6.97], P = 0.015) predicted higher risk of conversion than no use. Co-use predicted conversion risk even when it did not correspond to worse symptom severity at baseline. These findings underscore the need for targeted strategies to address co-use in clinical high-risk populations to reduce potential long-term psychiatric harm.