Anandamide modulation of endotoxin-induced inflammation

Abstract

The endocannabinoid system is comprised of the CB1 and CB2 receptors, the naturally occurring endogenous ligands, anandamide (AEA) and 2-arachidonyl glycerol (2-AG); and the enzymes involved in their synthesis and degradation. The enzyme fatty acid amide hydrolyase (FAAH) preferentially metabolises AEA, and the related N-acylethanolamines, N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA). While PEA and OEA do not have activity at CB1/2 receptors, they are capable of enhancing AEA signaling by competing with AEA at the catalytic site on the FAAH enzyme. All elements of the endocannabinoid system are widely and densely expressed in the mammalian immune system and brain and as such represent an important therapeutic target for a number of peripheral and central inflammatory disorders [1-3].