Cannabis use and duration of untreated psychosis: a systematic review of clinical predictors and neurobiological correlates

Background Duration of untreated psychosis (DUP) is an established prognostic factor in first-episode psychosis, and cannabis use is highly prevalent in these populations, yet whether and in which direction the two are related remains unclear. Objective To review the evidence on cannabis use and DUP in first-episode psychosis, with attention to how exposure and outcome have been defined. Methods Five databases were searched for observational studies reporting DUP in relation to cannabis use, either directly or alongside other variables. Quality was appraised with Newcastle-Ottawa Scale, and findings were synthesised narratively. Results Twenty-three studies were included, with samples ranging from 33 to 1,266 patients. The direction of the associations varied with the definition of exposure. Among studies assessing current or recent use, one small sample reported a significantly shorter DUP and two pointed in the same direction, whereas the two largest samples reported a longer untreated period and several found no difference. Among studies assessing lifetime use or a cannabis use disorder, none reported a shorter DUP. Both studies examining adolescents reported longer DUP among users, and where cannabis was analysed jointly with social or genetic moderators its association depended on the context of use. Smaller unadjusted samples tended to favour shorter DUP, larger representative ones did not. Conclusions The evidence does not support a consistently shorter DUP among cannabis users. The direction of the association appears to depend on how exposure is defined, on age and on setting, and the variability in the operationalisation of DUP further limits comparability.