The association between major depressive disorder and cannabis use disorder: A meta-analysis and meta-regression analysis.

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.