Anandamide

Anandamide (also known as N-arachidonoylethanolamine or AEA), is a fatty acid neurotransmitter derived from the non-oxidative metabolism of eicosatetraenoic acid (arachidonic acid), an essential ω-6 polyunsaturated fatty acid. The name is taken from the Sanskrit word ananda, which means 'joy, bliss, delight', and amide. It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways. It is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. As such, inhibitors of FAAH lead to elevated anandamide levels and are being pursued for therapeutic use. Anandamide (also known as N-arachidonoylethanolamine or AEA), is a fatty acid neurotransmitter derived from the non-oxidative metabolism of eicosatetraenoic acid (arachidonic acid), an essential ω-6 polyunsaturated fatty acid. The name is taken from the Sanskrit word ananda, which means 'joy, bliss, delight', and amide. It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways. It is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. As such, inhibitors of FAAH lead to elevated anandamide levels and are being pursued for therapeutic use. Anandamide was first described (and named) in 1992 by Raphael Mechoulam and his lab members W. A. Devane and Lumír Hanuš. Anandamide's effects can occur in either the central or peripheral nervous system. These distinct effects are mediated primarily by CB1 cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery. The latter are mainly involved in functions of the immune system. Cannabinoid receptors were originally discovered as being sensitive to Δ9-tetrahydrocannabinol (Δ9-THC, commonly called THC), which is the primary psychoactive cannabinoid found in cannabis. The discovery of anandamide came from research into CB1 and CB2, as it was inevitable that a naturally occurring (endogenous) chemical would be found to affect these receptors. Anandamide has been shown to impair working memory in rats. Studies are under way to explore what role anandamide plays in human behavior, such as eating and sleep patterns, and pain relief. Anandamide is also important for implantation of the early stage embryo in its blastocyst form into the uterus. Therefore, cannabinoids such as Δ9-THC might influence processes during the earliest stages of human pregnancy. Peak plasma anandamide occurs at ovulation and positively correlates with peak estradiol and gonadotrophin levels, suggesting that these may be involved in the regulation of AEA (anandamide) levels. Subsequently, anandamide has been proposed as a biomarker of infertility, but so far lacks any predictive values in order to be used clinically. Anandamide plays a role in the regulation of feeding behavior, and the neural generation of motivation and pleasure. In addition, anandamide injected directly into the forebrain reward-related brain structure nucleus accumbens enhances the pleasurable responses of rats to a rewarding sucrose taste, and enhances food intake as well. Moreover, the acute beneficial effects of exercise (termed as runner's high) seem to be mediated by anandamide in mice. Anandamide is the precursor of a class of physiologically active substances, the prostamides. Anandamide inhibits human breast cancer cell proliferation. Anandamide is found in chocolate together with two substances that might mimic the effects of anandamide, N-oleoylethanolamine and N-linoleoylethanolamine. Additionally, anandamide and other endocannabinoids are found in the model organism Drosophila melanogaster (fruit fly), although no CB receptors have been found in any insects. In humans, anandamide is biosynthesized from N-arachidonoyl phosphatidylethanolamine (NAPE). In turn NAPE arises by transfer of arachidonic acid from lecithin to the free amine of cephalin through an N-acyltransferase enzyme. Anandamide synthesis from NAPE occurs via multiple pathways and includes enzymes such as phospholipase A2, phospholipase C and NAPE-PLD.