The association between Major Depressive Disorder and Cannabis Use Disorder: a meta-analysis and meta-regression analysis

Major Depressive Disorder (MDD) and Cannabis Use Disorder (CUD) frequently co-occur, yet prevalence estimates vary widely across settings. This meta-analysis updates the evidence on the bidirectional association between MDD and CUD, emphasizing current-diagnosis subgroups, which are the most clinically relevant. Following PRISMA and MOOSE guidelines, we systematically searched PubMed, Google Scholar, and SciELO. Random-effects models estimated current-diagnosis prevalence of MDD among individuals with CUD and of CUD among individuals with MDD. Subgroup analyses differentiated psychiatric and community samples. Sensitivity analyses (leave-one-out) and Egger’s tests assessed robustness and publication bias. Meta-regressions evaluated demographic, methodological, and geographic moderators. In total, 55 studies comprising 3,279,774 individuals were included (454,547 and 112,328 living with CUD and MDD, respectively). Current MDD prevalence among individuals with CUD was elevated in both psychiatric samples (19.24%) and community samples (21.65%), indicating consistent comorbidity across settings. Current CUD prevalence among individuals with MDD showed stronger contextual variation, being substantially higher in psychiatric populations (28.45%) compared with community samples (4.61%). Sensitivity analyses demonstrated stable estimates across model specifications, although psychiatric samples exhibited greater variance. Studies with older populations and using ICD-10 (compared to DSM) presented higher MDD prevalence among individuals living with CUD in meta-regression models. Egger’s tests revealed no consistent evidence of publication bias. Current-diagnosis estimates highlight a strong and clinically meaningful bidirectional association between MDD and CUD. Differences between psychiatric and community samples—especially the markedly higher current CUD prevalence in patients with MDD—underscore the need for systematic screening across treatment settings. Future work should improve diagnostic differentiation, particularly regarding the overlap between depressive symptoms and cannabis withdrawal.