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. We used the North American Prodrome Longitudinal Study 2, a multi-site 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 substance use, 5) CHR without substance use, and 6) healthy controls. Among 1,014 participants (734 CHR, 280 controls), more frequent cannabis and tobacco use was linked to greater psychiatric symptom severity, including psychosis, anxiety, and depression. In survival analyses, co-use (HR = 2.53, 95% CI [1.44 to 4.45], p = .001), especially heavy co-use (HR = 3.63, 95% CI: 1.53 to 8.63, p = 0.003), was associated with increased risk of conversion to psychosis. Co-use of tobacco and cannabis was not associated with psychiatric symptom severity but did predict higher risk of conversion to psychosis. The combination of cannabis and tobacco use may exert a synergistic effect, amplifying conversion risk more than either substance alone, or may be a marker of an elevated underlying psychosis risk. These results highlight the need for early intervention strategies that address co-use in CHR populations to mitigate potential long-term psychiatric consequences.

The authors have declared no competing interest.

This work was supported by a National Institutes of Health (NIH) grants U01 MH066134 to Dr. Addington, P50 MH066286 to Dr. Bearden, U01 MH081944 to Dr. Cadenhead, U01 MH081902 to Dr. Cannon, U01 MH081857 to Dr. Cornblatt, R01 MH076989 to Dr. Mathalon, U01 MH066069 to Dr. Perkins, U01 MH081928 to Dr. Stone, and U01 MH081988 to Dr. Walker, U01 MH82022 to Dr. Woods, R01 MH116170 to Dr. Brady, and K23DA059690 to Dr. Ward. Stipend support for Ms. Blyth was provided by the National Institute on Alcohol Abuse and Alcoholism of the NIH under Award Number T32AA013525. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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