anandamide

Anandamide, or N-arachidonoylethanolamine (AEA), is an endogenous lipid mediator and one of the principal endocannabinoids in the nervous system. It binds to cannabinoid receptors CB1 and CB2 with high affinity and acts as a retrograde signaling molecule to modulate synaptic transmission.

It is synthesized on demand from membrane phospholipid precursors, notably N-acyl phosphatidylethanolamines (NAPE), through the action of NAPE-specific phospholipase D (NAPE-PLD) and related enzymes. It is a lipophilic molecule that is not stored in vesicles but produced when needed. It is rapidly degraded by the enzyme fatty acid amide hydrolase (FAAH) into arachidonic acid and ethanolamine; this rapid hydrolysis limits its duration of action.

Although most of its effects are mediated by CB1 receptor activation in the central nervous system, anandamide also interacts with other targets, including the vanilloid receptor TRPV1 and possibly peroxisome proliferator-activated receptors (PPARs).

Physiologically, anandamide is implicated in pain modulation, appetite regulation, mood, memory, and stress responses. It also participates in synaptic plasticity, such as short-term modulation of neurotransmitter release.

Anandamide was identified in the early 1990s by researchers studying the endocannabinoid system; its discovery helped establish endocannabinoids as endogenous brain signaling molecules. The name derives from the Sanskrit word ananda, meaning bliss.