(Endo)cannabinoid neurons (CB)
Anandamide (N-arachidonoyl-ethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the endogenous ligands for cannabinoid receptors. These ligands are lipid-like. Formation of anandamide occurs through phosphodiesterase-mediated cleavage of a phospholipid precursor (N-arachidonoyl-phosphatidylethanolamine).
AEA and 2-AG are released from post-synaptic neurons in a calcium ion-dependent manner.
Cannabinoid receptor-1 (CB1) is a Gi-coupled receptor which is localised presynaptically. Once activated, the receptor inhibits the adenylate cyclase activity and thus decreases the formation of second messenger cAMP. This results in a decreased inflow of calcium and a subsequent decrease in release of synaptic vesicles. GABA and glutamate are the major neurotransmitters regulated in this way by the CB1.