Risk-thresholds for the association between frequency of cannabis use and the development of psychosis: a systematic review and meta-analysis.

Background: Epidemiological studies show a dose-response association between cannabis use and the risk of psychosis. This review aimed to determine whether there are identifiable risk-thresholds between the frequency of cannabis use and psychosis development. Methods: Systematic search of Embase, MEDLINE, PsycINFO, CINAHL, and Web of Science for relevant studies (1 January 2010-26 April 2021). Case-control or cohort studies that investigated the relationship between cannabis use and the risk of psychosis development that reported effect estimates [odds ratios (OR), hazard ratios (HR), risk ratios (RR)] or the raw data to calculate them, with information on the frequency of cannabis consumption were included. Effect estimates were extracted from individual studies and converted to RR. Two-stage dose-response multivariable meta-analytic models were utilized and sensitivity analyses conducted. The Newcastle Ottawa Scale was used to assess the risk of bias of included studies. Results: Ten original (three cohorts, seven case-control) studies were included, including 7390 participants with an age range of 12-65 years. Random-effect model meta-analyses showed a significant log-linear dose-response association between cannabis use frequency and psychosis development. A restricted cubic-splines model provided the best fit for the data, with the risk of psychosis significantly increasing for weekly or more frequent cannabis use [RR = 1.01, 95% confidence interval (CI) 0.93-1.11 yearly; RR = 1.10, 95% CI 0.97-1.25 monthly; RR = 1.35, 95% CI 1.19-1.52 weekly; RR = 1.76, 95% CI 1.47-2.12 daily]. Conclusion: Individuals using cannabis frequently are at increased risk of psychosis, with no significant risk associated with less frequent use. Public health prevention messages should convey these risk-thresholds, which should be refined through further work.