Associations of cannabis use, tobacco use, and incident anxiety, mood, and psychotic disorders: a systematic review and meta-analysis.

Background: Observational studies consistently report associations between tobacco use, cannabis use and mental illness. However, the extent to which this association reflects an increased risk of new-onset mental illness is unclear and may be biased by unmeasured confounding. Methods: A systematic review and meta-analysis (CRD42021243903). Electronic databases were searched until November 2022. Longitudinal studies in general population samples assessing tobacco and/or cannabis use and reporting the association (e.g. risk ratio [RR]) with incident anxiety, mood, or psychotic disorders were included. Estimates were combined using random-effects meta-analyses. Bias was explored using a modified Newcastle-Ottawa Scale, confounder matrix, E-values, and Doi plots. Results: Seventy-five studies were included. Tobacco use was associated with mood disorders (K = 43; RR: 1.39, 95% confidence interval [CI] 1.30-1.47), but not anxiety disorders (K = 7; RR: 1.21, 95% CI 0.87-1.68) and evidence for psychotic disorders was influenced by treatment of outliers (K = 4, RR: 3.45, 95% CI 2.63-4.53; K = 5, RR: 2.06, 95% CI 0.98-4.29). Cannabis use was associated with psychotic disorders (K = 4; RR: 3.19, 95% CI 2.07-4.90), but not mood (K = 7; RR: 1.31, 95% CI 0.92-1.86) or anxiety disorders (K = 7; RR: 1.10, 95% CI 0.99-1.22). Confounder matrices and E-values suggested potential overestimation of effects. Only 27% of studies were rated as high quality. Conclusions: Both substances were associated with psychotic disorders and tobacco use was associated with mood disorders. There was no clear evidence of an association between cannabis use and mood or anxiety disorders. Limited high-quality studies underscore the need for future research using robust causal inference approaches (e.g. evidence triangulation).