2-Arachidonoylglycerol (2-AG)

2-arachidonoylglycerol, or 2-AG, is an endogenous lipid signaling molecule and one of the major endocannabinoids produced by the body. It is formed from membrane-derived lipid precursors and can activate both CB1 and CB2 cannabinoid receptors. In many tissues, 2-AG concentrations are higher than those of the other widely studied endocannabinoid, anandamide .¹

In the nervous system, 2-AG is often synthesized on demand in a postsynaptic cell and travels backward across the synapse. By activating presynaptic CB1 receptors, it can reduce release of conventional neurotransmitters. This retrograde signaling helps fine-tune synaptic strength and can operate over short time scales in response to neuronal activity .^1,2

2-AG should be distinguished from plant cannabinoids and from anandamide. It is made naturally in human tissues, is chemically a monoacylglycerol, and generally behaves as a full agonist at CB1 and CB2 receptors in experimental systems. Anandamide is a different lipid with different synthesis and degradation pathways and receptor pharmacology. 2-AG signaling is terminated mainly through enzymatic breakdown, especially by monoacylglycerol lipase, which helps keep the signal local and time-limited .^1,2