It has recently been recognized that peroxisome proliferator-activated receptors (PPAR) — which are known to be involved in metabolism and other cellular functions in many internal organs — also comprise a cannabinoid-like signaling system in the brain (1). Like the endogenous cannabinoid anandamide, the fatty acid amides oleoylethanolamide and palmitoylethanolamide (OEA and PEA) are endogenous ligands for the alpha subtype of the PPAR receptor (PPAR-α), are synthesized on demand, and are primarily degraded by fatty acid amide hydrolase (FAAH). Drugs that selectively inhibit FAAH prevent degradation and increase brain levels of anandamide, OEA, and PEA (2,3). But, unlike anandamide, OEA and PEA are devoid of action at cannabinoid receptors (4-6).
