of a depressive episode [169]. Perturbations affecting the levels of eCBs seem to affect depression and anxiety symptomatology in humans and associated behaviors in animal models. In severe mood disorders, such as MDD and BD, decreases in eCBs and/or cannabinoid receptor signaling have been shown, whereas increasing the endocannabinoid tone seems to be beneficial in reducing depressive and anxiogenic behavior and symptoms. This has been shown by different approaches, including by preventing eCB degradation by inhibitors for FAAH and preventing eCB action by antagonism of CB1R. One clear example, mentioned above, is the distinct insight provided from CB1R blockade using rimonabant as an anti-obesity drug, which necessitated its removal from the market because of induction of severe symptoms of depression and suicidality. In addition, SNPs for two major players in the ECS, FAAH and CB1R, were linked to depression and anxiety.
