Cannabis and tobacco co-use predicts psychosis in clinical high risk cohorts

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.