2-Arachidonoylglycerol (2-AG)

2-Arachidonoylglycerol, or 2-AG, is the most abundant endocannabinoid in the body, a lipid messenger that fully activates both CB1 and CB2 receptors.

2-AG is made on demand from membrane diacylglycerol by the enzyme DAGL and is broken down mainly by MAGL, so its concentration at any moment reflects the balance of those two enzymes. It is present in the brain at levels many times higher than anandamide and, unlike anandamide, it is a full agonist at cannabinoid receptors. Its best-understood job is retrograde signaling: a receiving neuron releases it, it crosses back to the sending terminal and, through CB1, briefly reduces glutamate or GABA release.

Beyond the synapse, 2-AG produced by immune cells acts on CB2 to influence inflammation, and its breakdown product arachidonic acid feeds prostaglandin synthesis, linking endocannabinoid and classic inflammatory chemistry. Researchers measure it with mass spectrometry in blood and tissue. CBD has no established direct effect on 2-AG levels, and its relevance to CBD pharmacology remains a matter of ongoing study.