Because depression and anxiety commonly accompany multiple other disorders, their etiology can be diverse and includes perturbations of multiple systems, in different brain regions; thus, it is difficult to identify the specific roles of cannabinoids in the induction or relief of depression and anxiety. In order to clarify this and simplify the analysis, we propose to approach this review of the role of cannabinoids in depression/anxiety in different sections as follows. First, preclinical data related to cannabinoids and depression- and anxiety-like effects, and stress in animal studies, followed by description of the perturbations of the ECS in humans with depression/anxiety. A third part will highlight the most relevant clinical observations obtained from long-time users of cannabis. Finally, a brief review of the clinical observations resulting from the use of cannabinoids to combat major depression disease (MDD), bipolar disease (BD), and depression/anxiety comorbid with other diseases.
