Editing Anandamide (section)

== Metabolism ==

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]] (FAAH), which breaks it down into free [[arachidonic acid]] and [[ethanolamine]]. Studies of piglets show that dietary levels of arachidonic acid and other [[essential fatty acids]] affect the levels of anandamide and other endocannabinoids in the brain.<ref name="pmid11353819">{{cite journal | vauthors = Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, Di Marzo V | title = Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 11 | pages = 6402–6406 | date = May 2001 | pmid = 11353819 | pmc = 33480 | doi = 10.1073/pnas.101119098 | doi-access = free | bibcode = 2001PNAS...98.6402B }}</ref> High fat diet feeding in mice increases levels of anandamide in the liver and increases [[lipogenesis]].<ref name="pmid15864349">{{cite journal | vauthors = Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G | title = Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity | journal = The Journal of Clinical Investigation | volume = 115 | issue = 5 | pages = 1298–1305 | date = May 2005 | pmid = 15864349 | pmc = 1087161 | doi = 10.1172/JCI23057 }}</ref> Anandamide may be relevant to the development of obesity, at least in rodents.

[[Paracetamol]] (known as acetaminophen in the US and Canada) is metabolically combined with arachidonic acid by FAAH to form [[AM404]].<ref name=AM404>{{cite journal | vauthors = Högestätt ED, Jönsson BA, Ermund A, Andersson DA, Björk H, Alexander JP, Cravatt BF, Basbaum AI, Zygmunt PM | title = Conversion of acetaminophen to the bioactive N-acylphenolamine AM404 via fatty acid amide hydrolase-dependent arachidonic acid conjugation in the nervous system | journal = The Journal of Biological Chemistry | volume = 280 | issue = 36 | pages = 31405–31412 | date = September 2005 | pmid = 15987694 | doi = 10.1074/jbc.M501489200 | doi-access = free }}</ref> This metabolite is a potent [[agonist]] at the [[TRPV1]] vanilloid receptor, a weak agonist at both CB<sub>1</sub> and CB<sub>2</sub> receptors, and an inhibitor of anandamide reuptake. Consequently, anandamide levels in the body and brain are elevated. Thus, paracetamol acts as a pro-drug for a cannabimimetic metabolite, which may be partially or fully responsible for its [[analgesic]] effects.<ref name="pmid17227290">{{cite journal | vauthors = Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S | title = Paracetamol: new vistas of an old drug | journal = CNS Drug Reviews | volume = 12 | issue = 3–4 | pages = 250–275 | date = September 2006 | pmid = 17227290 | pmc = 6506194 | doi = 10.1111/j.1527-3458.2006.00250.x }}</ref><ref name="pmid19053765">{{cite journal | vauthors = Sinning C, Watzer B, Coste O, Nüsing RM, Ott I, Ligresti A, Di Marzo V, Imming P | title = New analgesics synthetically derived from the paracetamol metabolite N-(4-hydroxyphenyl)-(5Z,8Z,11Z,14Z)-icosatetra-5,8,11,14-enamide | journal = Journal of Medicinal Chemistry | volume = 51 | issue = 24 | pages = 7800–7805 | date = December 2008 | pmid = 19053765 | doi = 10.1021/jm800807k }}</ref>

Black pepper contains the alkaloid [[guineesine]], which is an anandamide reuptake inhibitor. It may therefore increase anandamide's physiological effects.<ref>{{cite journal | vauthors = Nicolussi S, Viveros-Paredes JM, Gachet MS, Rau M, Flores-Soto ME, Blunder M, Gertsch J | title = Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice | journal = Pharmacological Research | volume = 80 | pages = 52–65 | date = February 2014 | pmid = 24412246 | doi = 10.1016/j.phrs.2013.12.010 }}</ref>