Although the literature on the role of CB1R antagonists and CB1R-knockout mice in addiction is wide ranging [157], the US Food and Drug Administration rejected rimonabant (SR141716), a CB1R antagonist/inverse agonist, for the treatment of obesity and nicotine dependence, due to its adverse psychiatric effects, including an increased risk of depression, anxiety, and suicidality [158,159]. Here, CNR1 is linked to major depressive disorder.