Endocannabinoid

Endocannabinoids are endogenous lipid signaling molecules that activate cannabinoid receptors. The two best-characterized are anandamide (AEA), isolated by Devane et al. (1992, Science 258:1946), and 2-arachidonoylglycerol (2-AG), identified independently by Mechoulam et al. (1995, Biochemical Pharmacology 50:83) and Sugiura et al. (1995). Both derive from arachidonic acid–containing membrane phospholipids and are synthesized on demand rather than stored in vesicles. Several congeners — N-arachidonoyldopamine (NADA), virodhamine, and 2-arachidonoylglyceryl ether (noladin ether) — have been described, though their physiological significance is less established. Endocannabinoids mediate retrograde synaptic signaling, modulate pain, appetite, mood, memory, immunity, and energy balance, and are rapidly degraded by FAAH (AEA) and MAGL (2-AG). → See also: Anandamide, 2-AG, Retrograde signaling, FAAH, MAGL.