anandamid

Anandaamide, or N-arachidonoylethanolamine (AEA), is an endogenous cannabinoid that acts as a ligand for the CB1 and CB2 receptors. It is a fatty acid amide produced on demand in the brain and other tissues, where it modulates synaptic transmission and participates in a range of physiological processes including pain, mood, appetite, and inflammation.

Biosynthesis and degradation: Anandamide is synthesized from membrane lipids, primarily from N-acyl phosphatidylethanolamines by the enzyme NAPE-PLD, with additional pathways described in the literature. It is rapidly inactivated mainly by fatty acid amide hydrolase (FAAH), which hydrolyzes it to arachidonic acid and ethanolamine. Cellular uptake mechanisms are debated, and some degradation can occur via cyclooxygenase-2 (COX-2) or lipoxygenases under certain conditions.

Receptors and targets: Anandamide activates CB1 receptors, which are abundant in the central nervous system, and CB2 receptors in peripheral tissues and immune cells, influencing analgesia, reward, anxiety, appetite, memory, and immune function. It can also interact with non-cannabinoid targets, such as the transient receptor potential vanilloid 1 (TRPV1) channel, and modulate other neurotransmitter systems.

Discovery and naming: Anandamide was identified in 1992 by researchers studying endogenous ligands for cannabinoid receptors. The name derives from the Sanskrit word ananda, meaning bliss. It is chemically known as N-arachidonoylethanolamine (AEA).

Significance: As a key endogenous endocannabinoid, anandamide is a major focus of research into pain, mood, and inflammatory disorders. Pharmacological strategies such as FAAH inhibitors aim to enhance anandamide signaling, but clinical success has been limited by delivery, stability, and off-target effects.