Enhancement of endocannabinoid signaling and the pharmacotherapy of depression

Cannabinoids are well known modulators of mood and emotional behavior. Current research supports a role for endocannabinoid signaling in the treatment of depression. Changes in levels of the cannabinoid CB1 receptor or the endogenous CB1 receptor ligands, anandamide and 2-AG, are observed both in humans suffering from depression and in animal models of depression, and experimental manipulation of CB1 receptor signaling has also been shown to affect emotional reactivity in rodents. Importantly, inhibitors of anandamide inactivation have demonstrated efficacy in enhancing stress-coping and mood-related behavior. This article will review these areas of research, highlighting the potential of endocannabinoid metabolism modulators as therapeutics for the treatment of depression.