cannabinoid receptors. The first such lipid to be isolated was anandamide which is the arachidonoyl amide of ethanolamine. Anandamide is formed via enzymatic release from N-arachidonoyl phosphatidylethanolamine by the N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Anandamide activates both the CB1 receptor, found primarily in the central nervous system, and the CB2 receptor which is found primarily in lymphocytes and the periphery. It is found at very low levels (nM) in most tissues and is inactivated by the fatty acid amide hydrolase. Subsequently, another endocannabinoid was isolated, 2-arachidonoylglycerol, which is produced when phospholipase C releases diacylglycerol which is then converted to 2-AG by diacylglycerol lipase. 2-AG can also activate both cannabinoid receptors and is inactivated by monoacylglycerol lipase. It is present at approximately 100-times the concentration of anandamide in most tissues. Elevations in either of these lipids causes analgesia and anti-inflammation and tissue protection during states of ischemia, but the precise roles played by these various endocannabinoids are still not totally known and intensive research into their function, metabolism, and regulation is ongoing. One saturated lipid from this class, often called an endocannabinoid, but with no relevant affinity for the CB1 and CB 2 receptor is palmitoylethanolamide. This signaling lipid has great affinity for the GRP55 receptor and the PPAR alpha receptor. It has been identified as an anti-inflammatory compound already in 1957, and as an analgesic compound in 1975. Rita Levi-Montalcini first identified one of its biological mechanisms of action, the inhibition of activated mast cells. Palmitoylethanolamide is the only endocannabinoid available on the market for treatment, as a food supplement. Prostaglandins Prostaglandins are formed through oxidation of arachidonic acid by cyclooxygenases and other prostaglandin synthases. There are currently nine known G-protein coupled receptors (eicosanoid receptors) that largely mediate prostaglandin physiology (although some prostaglandins activate nuclear receptors, see below). FAHFA FAHFAs (fatty acid esters of hydroxy fatty acids) are formed in adipose tissue, improve glucose tolerance and also reduce adipose tissue inflammation. Palmitic acid esters of hydroxy-stearic acids (PAHSAs) are among the most bioactive members able to activate G-protein coupled receptors 120. Docosahexaenoic acid ester of hydroxy-linoleic acid (DHAHLA) exert anti-inflammatory and pro-resolving properties. Retinol derivatives Retinaldehyde is a retinol (vitamin A) derivative responsible for vision. It binds rhodopsin, a well-characterized GPCR that binds all-cis retinal in its inactive state. Upon photoisomerization by a photon the cis-retinal is converted to trans-retinal causing activation of rhodopsin which ultimately leads to depolarization of