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Longitudinal Relationships Between Cannabis and Tobacco Use and Symptom Severity in Individuals at Clinical High Risk for Psychosis

Yunong Bai, Simon N. Vandekar, Brandee Feola, Jean Addington, Carrie E. Bearden, Kristin Cadenhead, Tyrone D. Cannon, Barbara Cornblatt, Matcheri S Keshavan, Daniel H. Mathalon, Diana O. Perkins, Larry Seidman, William S. Stone, Ming T. Tsuang, Elaine F. Walker, Scott W. Woods, Ricardo E Carrión, Heather Burrell Ward

DOI: 10.64898/2026.03.16.26347411 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Longitudinal
Sample size 764
Population Individuals at clinical high risk for psychosis (CHR-P) in the North American Prodrome Longitudinal Study (NAPLS2) cohort
Duration Participants were assessed every 6 months over two years.
Topics Cannabis
Key findings Heavier tobacco and cannabis use at a visit predicted worse anxiety at the next visit (tobacco: β=0.178; cannabis: β=0.162), while better social functioning predicted heavier later tobacco and cannabis use. Heavier baseline cannabis use predicted slower improvement of negative symptoms (β=0.159) and deterioration of role functioning (β=-0.046) over two years. The authors conclude that baseline cannabis use frequency predicts worse clinical trajectory, especially for negative symptoms.

Abstract

Abstract Objective Tobacco and cannabis are the most used substances among individuals at clinical high risk for psychosis (CHR-P), but it remains controversial whether substance use drives symptom exacerbation and psychosis transition, or vice versa. We investigated longitudinal dose-response relationships of tobacco and cannabis use with clinical presentation in a CHR-P population.

Methods: Data was obtained from the North American Prodrome Longitudinal Study (NAPLS2) CHR-P cohort (n=764). Participants were assessed every 6 months over two years. Substance use frequency, psychiatric symptoms (psychosis, depression, anxiety, and social anxiety), global social and role functioning, and neurocognitive performance were measured. Linear mixed effect models were used to model the relationship between substance use and clinical measurements across visits, and that between baseline use and trajectory of symptoms, functioning, and cognition.

Results: Psychiatric symptoms, functioning, and cognitive performance improved, while tobacco and cannabis use frequency did not change over two years for CHR-P individuals in NAPLS2. Heavier tobacco and cannabis use at current visit predicted worse anxiety at next visit (tobacco: β=0.178, p=0.033; cannabis: β=0.162, p=0.018). Better social functioning predicted heavier tobacco (β=0.178, p<0.001) and cannabis: (β=0.162, p<0.001) use at next visit. We observed a significant baseline cannabis-by-time interaction, where heavier baseline cannabis use predicted slower improvement of negative symptoms (β=0.159, p=0.0017, FDRp=0.0067) and deterioration of role function (β=-0.046, p=0.018).

Conclusions: In CHR-R, current tobacco and cannabis use predicted worse anxiety at future visits. Baseline cannabis use frequency predicts worse clinical trajectory, especially for negative symptoms.