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.

John McGrath, MD, PhD, FRANZCP; Joy Welham, MAPs; James Scott, MBBS, FRANZCP; Daniel Varghese, MBBS, FRANZCP; Louisa Degenhardt, PhD; Mohammad Reza Hayatbakhsh, MD, PhD; Rosa Alati, PhD; Gail M. Williams, PhD; William Bor, MBBS, DPM, FRANZCP; Jake M. Najman, PhD

Arch Gen Psychiatry. 2010;67(5):440-447. Published online March 1, 2010 (doi:10.1001/archgenpsychiatry.2010.6).

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.

 Author Affiliations: Queensland Brain Institute (Dr McGrath) and Department of Psychiatry (Drs McGrath and Scott), University of Queensland, St Lucia, Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol (Dr McGrath and Ms Welham), Child and Youth Mental Health Service, Royal Children’s Hospital (Dr Scott), School of Population Health (Drs Hayatbakhsh, Alati, Williams, and Najman), and Centre for Youth Substance Abuse Research (Dr Alati), University of Queensland, Herston, and Department of Psychiatry, Princess Alexandra Hospital, Woolloongabba (Dr Varghese), Queensland, National Drug and Alcohol Research Centre, University of New South Wales, Sydney (Dr Degenhardt), and Mater Children’s Hospital, South Brisbane (Dr Bor), Australia.