Anandamide (AEA)

Anandamide (N-arachidonoylethanolamine, AEA; C₂₂H₃₇NO₂) is the first discovered endocannabinoid, isolated from porcine brain by Devane, Hanuš, Mechoulam, and colleagues (1992, Science 258:1946). Its name derives from Sanskrit "ānanda" ("bliss") and the amide functional group. AEA is a partial agonist at CB1 (lower efficacy than Δ⁹-THC), a weaker partial agonist at CB2, and — notably — a full agonist at TRPV1 at higher concentrations (Zygmunt et al., 1999, Nature 400:452). It is synthesized postsynaptically from N-arachidonoyl phosphatidylethanolamine (NAPE) primarily by NAPE-PLD, released on demand, and rapidly hydrolyzed by FAAH to arachidonic acid and ethanolamine. Tonic AEA signaling influences mood, stress response, pain perception, and appetite; FAAH inhibitors and genetic FAAH variants (e.g., the common C385A/Pro129Thr polymorphism) are associated with reduced anxiety and altered pain sensitivity. → See also: FAAH, CB1 receptor, TRPV1, 2-AG.