Cannabis use and the risk for psychosis and affective disorders

Objective: This review discusses the relationship between cannabis use and psychotic, bipolar, depressive, and anxiety disorders, as well as suicide. It summarizes epidemiological evidence from cross-sectional and long-term prospective studies and considers possible etiological mechanisms. Methods: Systematic reviews and methodologically robust studies in the field (from inception to February 2019) were identified using a comprehensive search of Medline, PsychINFO, and Embase and summarized using a narrative synthesis. Results: Consistent evidence, both from observational and experimental studies, has confirmed the important role of cannabis use in the initiation and persistence of psychotic disorders. The size of the effect is related to the extent of cannabis use, with greater risk for early cannabis use and use of high-potency varieties and synthetic cannabinoids. Accumulating evidence suggests that frequent cannabis use also increases the risk for mania as well as for suicide. However, the effect on depression is less clear and findings on anxiety are contradictory with only a few methodologically robust studies. Furthermore, the relationship with common mental disorders may involve reverse causality, as depression and anxiety are reported to lead to greater cannabis consumption in some studies. Pathogenetic mechanisms focus on the effect of tetrahydrocannabinol (THC, the main psychoactive ingredient of cannabis) interacting with genetic predisposition and perhaps other environmental risk factors. Cannabidiol (CBD), the other important ingredient of traditional cannabis, ameliorates the psychotogenic effects of THC but is absent from the high-potency varieties that are increasingly available. Conclusions: The evidence that heavy use of high-THC/low-CBD types of cannabis increases the risk of psychosis is sufficiently strong to merit public health education. Evidence of similar but smaller effects in mania and suicide is growing, but is not convincing for depression and anxiety. There is much current interest in the possibility that CBD may be therapeutically useful.