Cannabis and tobacco co-use predicts psychosis in clinical high risk cohorts
Daniel Bello, Sophia H. Blyth, Rachel A Rabin, Jean Addington, Carrie E. Bearden, Kristin Cadenhead, Tyrone D. Cannon, Ricardo E Carrión, Barbara Cornblatt, Matcheri S Keshavan, Daniel H. Mathalon, D. Perkins, L. Seidman, William S. Stone, Ming T. Tsuang, Elaine F. Walker, S. Woods, R. Brady, H. Ward
Nature Mental Health May 1, 2026 DOI: 10.1038/s44220-026-00648-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort study Longitudinal Peer reviewed |
|---|---|
| Sample size | 1,012 |
| Population | Individuals at clinical high risk for psychosis and healthy controls from the North American Prodrome Longitudinal Study-2 |
| Topics | Cannabis |
| Key findings | Among CHR individuals, heavy cannabis and light tobacco co-use was associated with a higher risk of conversion to psychosis than no use of either substance (HR = 2.93, 95% CI [1.23–6.97]). Co-use was not associated with psychiatric symptom severity, but more frequent cannabis and tobacco use was linked to greater symptom severity. |
Abstract
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. In individuals at clinical high risk for psychosis, the concurrent use of cannabis and tobacco predicted an elevated risk of transitioning to psychosis. Heavy cannabis use combined with light tobacco use was linked to a threefold increase in the risk of transition.
Comparable studies
Other observational and cohort studies on cannabis, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population | 2009 | Case-control study | n = 454 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people | 2000 | Observational | |
| Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline | 2011 | Observational cohort | n = 1,923 |
| Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... | 2005 | Observational cohort | n = 535 |