Association Between Cannabis Use and Psychosis-Related Outcomes Using Sibling Pair Analysis in a Cohort of Young Adults

Context: Prospective cohort studies have identified an association between cannabis use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables. The use of sibling pair analysis reduces the influence of unmeasured residual confounding. Objective: To explore the association between cannabis use and psychosis-related outcomes. Design: A sibling pair analysis nested within a prospective birth cohort. Setting: Births at a Brisbane, Australia, hospital. Participants: Three thousand eight hundred one young adults born between 1981 and 1984 as part of the Mater-University Study of Pregnancy. Main Outcome Measures: Cannabis use and 3 psychosis-related outcomes (nonaffective psychosis, hallucinations, and Peters et al Delusions Inventory score) were assessed at the 21-year follow-up. Associations between duration since first cannabis use and psychosis-related outcomes were examined using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up. Within 228 sibling pairs, the association between within-pair differences in duration since first cannabis use and Peters et al Delusions Inventory score was examined with general linear modeling. The potential impact of attrition was examined. Results: Duration since first cannabis use was associated with all 3 psychosis-related outcomes. For those with duration since first cannabis use of 6 or more years, there was a significantly increased risk of (1) nonaffective psychosis (adjusted odds ratio, 2.2; 95% confidence interval, 1.1-4.5), (2) being in the highest quartile of Peters et al Delusions Inventory score (adjusted odds ratio, 4.2; 95% confidence interval, 4.2-5.8), and (3) hallucinations (adjusted odds ratio, 2.8; 95% confidence interval, 1.9-4.1). Within sibling pairs, duration since first cannabis use and higher scores on the Peters et al Delusions Inventory remained significantly associated. Conclusions: Early cannabis use is associated with psychosis- related outcomes in young adults. The use of sibling pairs reduces the likelihood that unmeasured confounding explains these findings. This study provides further support for the hypothesis that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.