BACKGROUND: Depression has been cited as a possible confounder, moderator, and mediator of the relationship between cannabis use and suicidal behaviours. We aimed to assess the role of depression in the relationship between cannabis use and suicidal behaviours by systematically reviewing existing literature in the general population.

METHODS: We systematically searched PubMed, Science Direct and PsycArticles from database inception to May 20th 2024, for quantitative observational studies investigating the role of depression in the association between cannabis use and suicidal behaviours. We conducted a meta-analysis to examine the confounding role of depression and search for qualitative arguments in favour of moderating and/or mediating roles of depression.

RESULTS: We screened 1081 articles, selected 43 for full-text screening and finally included 25. Among adolescents, cannabis use was associated with suicidal ideation (OR = 1.46 [1.17, 1.83]) and suicide attempts (OR = 2.17 [1.56, 3.03]) in studies adjusting for depression. Among adults, cannabis use was associated with suicidal ideation (OR = 1.78 [1.28, 2.46]) in studies adjusting for depression. 12 out of 25 studies found no association between cannabis use and suicidality after adjustment for depression. Six studies investigated a potential moderating role of depression, with four reporting significant but conflicting results. No article investigated the mediating role of depression.

DISCUSSION: There is a clear relationship between cannabis use and suicidal behaviours, which is partly confounded by depression. Studies investigating a moderating role of depression did not agree about the direction of moderation. Further research using methodologies that consider the chronology of events is needed.