The Anxiolytic Actions of 2-Arachidonoylglycerol: Converging Evidence from Two Recent Genetic Endocannabinoid Deficiency Models.

The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) is a lipid-signaling molecule synthesized in the central nervous system primarily by diacylglycerol lipase alpha (DAGLA) that exerts biological actions primarily via activation of CB1 type cannabinoid receptors. CB1 is the primary target of Δ9-tetrahydrocannabinol, and anxiety reduction and tension relief have been reported as primary motives for chronic cannabis use (1). Consistent with this, pharmacologic augmentation of 2-AG levels reduces anxiety-like and depressive behaviors, and 2-AG levels increase in the amygdala in response to repeated stress exposure, suggesting a physiologic role for this signaling system in buffering against the development of stress-induced pathology (2).