2-Arachidonoylglycerol (2-AG)

2-Arachidonoylglycerol (2-AG) is an endogenous signaling lipid and the most abundant endocannabinoid found in the mammalian brain. Unlike anandamide, which is typically a partial agonist, 2-AG acts as a full agonist at both the cannabinoid type 1 (CB1) and type 2 (CB2) G protein-coupled receptors. It is synthesized on-demand from membrane phospholipids by diacylglycerol lipase (DAGL) and serves as a critical retrograde messenger, traveling backward from postsynaptic neurons to inhibit presynaptic neurotransmitter release. This mechanism allows 2-AG to modulate synaptic plasticity, alleviate chronic pain, and regulate neuroinflammation. Because it is primarily degraded by the enzyme monoacylglycerol lipase (MAGL), therapeutic strategies often focus on MAGL inhibition to elevate endogenous 2-AG levels, providing neuroprotective benefits while potentially avoiding the intense psychotropic side effects associated with direct CB1 receptor agonists.

Other names

Glyceryl 2-arachidonate2-Monoarachidonoylglycerol2-Arachidonylglycerol1,3-dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate

Full agonist at Cannabinoid receptor 1 (CB1) and Cannabinoid receptor 2 (CB2)