Anandamide

Anandamide
IUPAC name	(5Z,8Z,11Z,14Z)- N-(2-hydroxyethyl) icosa-5,8,11,14-tetraenamide or arachidonoylethanolamide
Identifiers
CAS number	[94421-68-8]
PubChem	5281969
MeSH	Anandamide
SMILES	CCCCC\C=C/C\C=C/C\C=C /C\C=C/CCCC(NCCO)=O
Properties
Molecular formula	C22H37NO2
Molar mass	347.53 g/mol
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Anandamide, also known as arachidonoylethanolamide or AEA, is an endogenous cannabinoid neurotransmitter found in animal and human organs, especially in the brain. It was isolated and its structure was elucidated by Czech analytical chemist Lumír Ondřej Hanuš and American molecular pharmacologist William Anthony Devane in the Laboratory of Raphael Mechoulam, at the Hebrew University in Jerusalem, Israel in 1992. The name is taken from the Sanskrit word ananda, which means "bliss, delight", and amide.Devane W. A., Hanuš L., Breuer A., Pertwee R. G., Stevenson L. A., Griffin G., Gibson D., Mandelbaum A., Etinger A., Mechoulam R.: Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946-1949 (1992)Mechoulam R., Fride E.: The unpaved road to the endogenous brain cannabinoid ligands, the anandamides in “Cannabinoid Receptors” (ed. R. Pertwee), Academic Press, London. Pp. 233-258 (1995) It is degraded by the fatty acid amide hydrolase (FAAH) enzyme which converts anandamide into the inactive ethanolamine and arachidonic acid. As such, inhibitors of FAAH lead to elevated anandamide levels and are being pursued for therapeutic use.

Cannabinoid receptors

Anandamide\'s effects can be either central, in the brain, or peripheral, in other parts of the body. These distinct effects are mediated primarily by CB1 cannabinoid receptors in the nervous system, and CB2 cannabinoid receptors in the periphery. The latter is mainly involved in functions of the immune system.

Cannabinoid receptors are part of the largest known family of receptors, the G protein-coupled receptors, which - in this case - has a distinctive pattern in which the receptor molecule spans the cell membrane seven times over. The CB1 receptor is one of the most numerous G protein-coupled receptors in the nervous 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 be involved in working memoryMallet PE, Beninger RJ. The endogenous cannabinoid receptor agonist anandamide impairs memory in rats. Behav Pharmacol. 1996; 7:276-284.. 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 interfere with the earliest stages of human pregnancyPiomelli D. THC: moderation during implantation. Nat Med. 2004 Jan;10(1):19-20. PMID 14702623.

Anandamide also is important in the regulation of feeding behavior, and the neural generation of motivation and pleasure. Both anandamide and exogenous cannabinoids like THC enhance food intake in animals and humans, an effect that is sometimes called the \'marijuana munchies.\' 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, anandamide is thought to be an endogenous ligand for vanilloid receptors (which are involved in the transduction of acute and inflammatory pain signals), activating the receptor in a PKC-dependent (protein kinase C-dependent) manner.

Raphael Mechoulam (right), discoverer of psychoactive compound, (-)-trans-delta-9-tetrahydrocannabinol, from Cannabis sativa L. (1964) and Lumír Ondřej Hanuš (left), discoverer of endogenous ligand, anandamide, from brain (1992). Both compounds bind to the cannabinoid receptors in the brain.

Endogenous and dietary sources

Anandamide occurs in minute quantities in sea urchin roe.Bisogno T, Ventriglia M, Milone A, Mosca M, Cimino G, Di Marzo V. Occurrence and metabolism of anandamide and related acyl-ethanolamides in ovaries of the sea urchin Paracentrotus lividus. Biochim Biophys Acta. 1997 Apr 21;1345(3):338-48. PMID 9150253 Anandamide was reported to be present in chocolateE. di Tomaso, M. Beltramo, D. Piomelli (1996). "Brain cannabinoids in chocolate". Nature 382 (6593): 677-678. doi:10.1038/382677a0. PMID 8751435.  in small quantitities that were not be assumed to have pharmacological or psychoactive effects.Di Marzo V, Sepe N, De Petrocellis L, et al (1998). "Trick or treat from food endocannabinoids?". Nature 396 (6712): 636–7. doi:10.1038/25267. PMID 9872309.  However, a later study failed to repeat these findings and did not detect anandamide in chocolate.GC Willi, A Berger, V Di Marzo, T Bisogno, L De (2001). "Lipids in Neural Function: Modulation of Behavior by Oral Administration of Endocannabinoids Found in Foods". Nestle Nutr Workshop Ser Clin Perform Programme 5: 169-84; discussion 185-7. PMID 11510437. 

The human body synthesizes anandamide from N-arachidonoyl phosphatidylethanolamine, which is itself made by transferring arachidonic acid from phosphatidylcholine (PC) to the free amine of phosphatidylethanolamine (PE).V Natarajan, PV Reddy, PC Schmid, HH Schmid, N-Acylation of ethanolamine phospholipids in canine myocardium, Biochem. Biophys. Acta, 1982, Vol 712, 342-355, PMID 7126608H Cadas, E di Tamaso, D Piomelli, Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain., J Neurosci, 1997, Vol 17(4), 1226-42. PMID 9006968 Endogenous anandamide is present at very low levels and has a very short half-life due to the action of the enzyme fatty acid amide hydrolase which breaks it down into free arachidonic acid and ethanolamine. Studies of piglets show that dietary levels of AA and other essential fatty acids affect the levels of anandamide and other endocannabinoids in the brain.Alvin Berger, Anandamide and diet: Inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets, PNAS, May 22, 2001 vol. 9, no. 11, http://www.pnas.org/cgi/content/abstract/98/11/6402

High fat diet feeding in mice increase levels of Anandamide in the liver and increase lipogenesis.Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G, Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity, J Clin Invest. 2005 May;115(5):1298-305. PMID: 15864349 This indicates that Anandamide plays a role in the development of obesity, at least in rodents.

A study lead in 1998 shows that anandamide inhibits human breast cancer cell proliferation.Luciano De Petrocellis, Dominique Melck, Antonella Palmisano, Tiziana Bisogno, Chiara Laezza, Maurizio Bifulco, Vincenzo Di Marzo. "The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation". 

See also

• Cannabinoids
• Tetrahydrocannabinol (THC)
• 2-Arachidonoylglycerol
• Fatty acid amide hydrolase

References

External links

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