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Cannabis and Tobacco Co-Use Is Associated With Impaired Neurocognitive Performance in Individuals at Clinical High Risk for Psychosis.

Daniel Bello, J. Connolly, Jean Addington, Carrie E. Bearden, Kristin Cadenhead, Tyrone D. Cannon, 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, Ricardo E Carrión, H. Ward

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging April 1, 2026 DOI: 10.1016/j.bpsc.2026.03.021 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Longitudinal Peer reviewed
Sample size 1,012
Population Individuals at clinical high risk for psychosis (CHR-P) and healthy control participants from the North American Prodrome Longitudinal Study 2 (NAPLS2)
Measures MATRICS Consensus Cognitive Battery, Seidman Auditory Continuous Performance Task
Topics Cannabis
Key findings Cannabis and tobacco co-use was associated with lower global cognitive performance and lower working memory, verbal learning, and attention compared with healthy controls. CHR-P participants who used no substances also had lower performance across multiple cognitive domains and the lowest social functioning. The authors propose that co-use may explain mixed associations between cannabis use and cognition in prior literature.

Abstract

Background: Cannabis use is highly prevalent among people with psychotic disorders. While there is some indication that cannabis use exacerbates psychosis symptoms, its neurocognitive effects remain unclear. Co-use of cannabis and tobacco is increasing in the general population, but little is known about its effects in people with psychosis or those at risk for developing a psychotic disorder, including its effects on cognitive performance.

Methods: We analyzed data from NAPLS2 (North American Prodrome Longitudinal Study 2), a multisite prospective study of individuals at clinical high risk for psychosis (CHR-P) and healthy control participants. Cognitive performance was assessed using the MATRICS Consensus Cognitive Battery and the Seidman Auditory Continuous Performance Task. We examined differences in cognitive performance across 6 study groups: 1) CHR-P tobacco use, 2) CHR-P cannabis use, 3) CHR-P co-use, 4) CHR-P with neither tobacco nor cannabis use, 5) CHR-P with no substance use, and 6) healthy control.

Results: Among 1012 participants (734 CHR-P, 278 healthy control), co-use of cannabis and tobacco was associated with lower global cognitive performance and lower working memory, verbal learning, and attentional performance compared with healthy control participants. CHR-P individuals who did not use substances also had lower cognitive performance across multiple measures, including global cognition, working memory, verbal learning, visual learning, and attentional performance. The CHR-P non-substance use group also had the lowest social functioning.

Conclusions: Cannabis and tobacco co-use is associated with lower neurocognitive performance, which may explain the mixed associations between cannabis use and cognitive performance in previous literature.

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

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