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(Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: SMILES1.)
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| ImageFile = aea.jpg
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| IUPACName = (5''Z'',8''Z'',11''Z'',14''Z'')- ''N''-(2-hydroxyethyl)<br>icosa-5,8,11,14-tetraenamide<br>or<br>arachidonoylethanolamide
| ImageFile = Anandamide_skeletal.svg
| OtherNames =
| ImageSize = 200px
| IUPACName = (5''Z'',8''Z'',11''Z'',14''Z'')-''N''-(2-hydroxyethyl)icosa-5,8,11,14-tetraenamide
| OtherNames = ''N''-arachidonoylethanolamine<!-- amine is actually correct here, despite pubchem (see talk page) --><br>arachidonoylethanolamide
| Section1 = {{Chembox Identifiers
| Section1 = {{Chembox Identifiers
|  CASNo = 94421-68-8
|  ChemSpiderID = 4445241
| InChI = 1/C22H37NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-22(25)23-20-21-24/h6-7,9-10,12-13,15-16,24H,2-5,8,11,14,17-21H2,1H3,(H,23,25)/b7-6-,10-9-,13-12-,16-15-
| InChIKey = LGEQQWMQCRIYKG-DOFZRALJBA
| SMILES1 = CCCCC/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)NCCO
| CASNo = 94421-68-8
|  PubChem = 5281969
|  PubChem = 5281969
|  SMILES = CCCCC\C=C/C\C=C/C\C=C<br>/C\C=C/CCCC(NCCO)=O
| IUPHAR_ligand = 2364
| IUPHAR_ligand = 737
|  SMILES = O=C(NCCO)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC
|  MeSHName = Anandamide
|  MeSHName = Anandamide
   }}
   }}
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[[Image:LumRaf.jpg|thumb|right|Raphael Mechoulam (right), discoverer of psychoactive compound, (-)-trans-delta-9-tetrahydrocannabionol, 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.]]
'''Anandamide''', also known as '''''N''-arachidonoylethanolamine'''  or '''AEA''', is an endogenous [[cannabinoids|cannabinoid]] [[neurotransmitter]]. It was isolated and its structure was first described by [[Czechs|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 (spirituality)|bliss]], [[delight]]", and [[amide]].<ref name="pmid1470919">{{cite journal | author = Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R | title = Isolation and structure of a brain constituent that binds to the cannabinoid receptor | journal = Science | volume = 258 | issue = 5090 | pages = 1946–9 | year = 1992 | month = December | pmid = 1470919 | doi = 10.1126/science.1470919| url = | issn = }}</ref><ref name="isbn0-12-551460-3">{{cite book | author =  Mechoulam R, Fride E | authorlink = | editor = Pertwee RG | others = | title = Cannabinoid receptors | edition = | language = | publisher = Academic Press | location = Boston | year = 1995 | origyear = | pages = 233–258 | chapter =  The unpaved road to the endogenous brain cannabinoid ligands, the anandamides | quote = | isbn = 0-12-551460-3 | oclc = | doi = | url = | accessdate = }}</ref> It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways.<ref name=wang2009>{{cite doi|10.1016/j.prostaglandins.2008.12.002}}</ref> 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.<ref>{{cite doi|10.1016/S0074-7742(09)85005-8}}</ref><ref>{{cite doi|10.1016/j.lfs.2009.06.003}}</ref>
{{SI}}
{{Editor Help}}


==Overview==
== Physiological functions ==


'''Anandamide''', also known as '''arachidonoylethanolamide'''  or '''AEA''', is an endogenous [[cannabinoids|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]]. <ref>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)</ref>  
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 receptor]]s 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 Δ<sup>9</sup>-[[tetrahydrocannabinol]] (Δ<sup>9</sup>-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.
<ref>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)</ref>  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==
Moreover, anandamide is thought to be an [[endogenous]] [[ligand (biochemistry)|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.{{Fact|date=January 2009}}
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 receptor]]s, 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.
Anandamide has been shown to be involved in working memory.<ref>{{cite journal | author = allet PE, Beninger RJ| title = The endogenous cannabinoid receptor agonist anandamide impairs memory in rats | url = http://www.behaviouralpharm.com/pt/re/bpharm/abstract.00008877-199605000-00008.htm | year = 1996 | journal = Behavioural Pharmacology | pages = 276–284 | volume = 7 | issue = 3 }}</ref> Studies are under way to explore what role anandamide plays in human behavior, such as eating and sleep patterns, and pain relief.


Cannabinoid receptors were originally discovered as being sensitive to Δ<sup>9</sup>-[[tetrahydrocannabinol]] (Δ<sup>9</sup>-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 is also important for implantation of the early stage [[embryo]] in its [[blastocyst]] form into the [[uterus]]. Therefore cannabinoids such as Δ<sup>9</sup>-THC might interfere with the earliest stages of human pregnancy.<ref name="pmid14702623">{{cite journal | author = Piomelli D | title = THC: moderation during implantation | journal = Nat. Med. | volume = 10 | issue = 1 | pages = 19–20 | year = 2004 | month = January | pmid = 14702623 | doi = 10.1038/nm0104-19 | url = | issn = }}</ref> 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 levels.<ref>{{cite journal |author=El-Talatini MR, Taylor AH, Konje JC |title=The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotrophins during the menstrual cycle |journal=Fertil. Steril. |volume=93 |issue=6 |pages=1989–96 |year=2010 |month=April |pmid=19200965 |doi=10.1016/j.fertnstert.2008.12.033 |url=}}</ref>


Anandamide has been shown to be involved in working memory<ref>Mallet PE, Beninger RJ. The endogenous cannabinoid receptor agonist anandamide impairs memory in rats. Behav Pharmacol. 1996; 7:276-284.</ref>. Studies are under way to explore what role anandamide plays in human behavior, such as eating and sleep patterns, and pain relief.
Anandamide also is important 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.<ref name="pmid17406653">{{cite journal | author = Mahler SV, Smith KS, Berridge KC | title = Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances 'liking' of a sweet reward | journal = Neuropsychopharmacology | volume = 32 | issue = 11 | pages = 2267–78 | year = 2007 | month = November | pmid = 17406653 | doi = 10.1038/sj.npp.1301376 | url = | issn = }}</ref>


Anandamide is also important for implantation of the early stage [[embryo]] in its [[blastocyst]] form into the [[uterus]]. Therefore cannabinoids such as Δ<sup>9</sup>-THC might interfere with the earliest stages of human pregnancy<ref>Piomelli D. THC: moderation during implantation. ''Nat Med''. 2004 Jan;10(1):19-20. PMID 14702623</ref>.
A study published in 1998 shows that anandamide inhibits human breast cancer cell proliferation.<ref name="pmid9653194">{{cite journal | author = De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M, Di Marzo V | title = The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 14 | pages = 8375–80 | year = 1998 | month = July | pmid = 9653194 | pmc = 20983 | doi = 10.1073/pnas.95.14.8375| url = | issn = }}</ref>


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.
[[Image:LumRaf.jpg|thumb|right|[[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.]]


Moreover, anandamide is thought to be an [[endogenous]] [[ligand (biochemistry)|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.
== Synthesis and degradation ==


==Endogenous and dietary sources==
The human body synthesizes anandamide from ''N''-arachidonoyl phosphatidylethanolamine (NAPE), which is itself made by transferring [[arachidonic acid]] from [[lecithin]] to the free amine of [[cephalin]] through an [[N-acyltransferase]] enzyme.<ref name="pmid7126608">{{cite journal | author = Natarajan V, Reddy PV, Schmid PC, Schmid HH | title = N-Acylation of ethanolamine phospholipids in canine myocardium | journal = Biochim. Biophys. Acta | volume = 712 | issue = 2 | pages = 342–55 | year = 1982 | month = August | pmid = 7126608 | doi = | url = | issn = }}</ref><ref name="pmid9006968">{{cite journal | author = Cadas H, di Tomaso E, Piomelli D | title = Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain | journal = J. Neurosci. | volume = 17 | issue = 4 | pages = 1226–42 | year = 1997 | month = February | pmid = 9006968 | doi = | url = | issn = }}</ref> Anandamide synthesis from NarPE occurs via multiple pathways and includes enzymes such as [[phospholipase A2]], [[phospholipase C]] and [[NAPE-PLD]]. <ref name=wang2009/>
Anandamide occurs in minute quantities in sea urchin roe<ref>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</ref>, though there is some controversy over whether they have any effects on the body in these quantities.
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 | author = 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 = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 11 | pages = 6402–6 | year = 2001 | month = May | pmid = 11353819 | pmc = 33480 | doi = 10.1073/pnas.101119098 | url = | issn = }}</ref> High fat diet feeding in mice increases levels of anandamide in the liver and increases [[lipogenesis]].<ref name="pmid15864349">{{cite journal | author = 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 = J. Clin. Invest. | volume = 115 | issue = 5 | pages = 1298–305 | year = 2005 | month = May | pmid = 15864349 | pmc = 1087161 | doi = 10.1172/JCI23057 | url = | issn = }}</ref> This suggests that anandamide may play a role in the development of obesity, at least in rodents.


The human body synthesizes anandamide from N-arachidonoyl phosphatidylethanolamine, which is itself made by transferring [[arachidonic acid]] from [[phospholipid|phosphatidylcholine (PC)]] to the free amine of [[phospholipid|phosphatidylethanolamine (PE)]].<ref>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 7126608</ref><ref>H 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</ref>  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. <ref>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</ref>
[[Paracetamol]] (or [[acetaminophen]] in the U.S.A.) is metabolically combined with arachidonic acid by FAAH to form [[AM404]].<ref name=AM404>{{cite doi|10.1074/jbc.M501489200}}</ref> This metabolite of paracetamol is a potent agonist at the [[TRPV1]] vanilloid receptor, a weak agonist at both CB1 and CB2 receptors, and an inhibitor of anandamide reuptake. As a result, anandamide levels in the body and brain are elevated. In this fashion, paracetamol acts as a [[pro-drug]] for a cannabimimetic metabolite. This action may be partially or fully responsible for the [[analgesic]] effects of paracetamol.<ref name="pmid17227290">{{cite journal | author = Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S | title = Paracetamol: new vistas of an old drug | journal = CNS Drug Rev | volume = 12 | issue = 3-4 | pages = 250–75 | year = 2006 | pmid = 17227290 | doi = 10.1111/j.1527-3458.2006.00250.x | url = | issn = }}</ref><ref name="pmid19053765">{{cite journal | author = 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 = J. Med. Chem. | volume = 51 | issue = 24 | pages = 7800–5 | year = 2008 | month = December | pmid = 19053765 | doi = 10.1021/jm800807k | url = | issn = }}</ref>  


==See also==
== See also ==
* [[Cannabinoids]]
* [[Cannabinoids]]
* [[Tetrahydrocannabinol]] (THC)
* [[Tetrahydrocannabinol]] (THC)
* [[2-Arachidonoylglycerol]]
* [[Fatty acid amide hydrolase]]
== References ==
{{Reflist|2}}
== External links ==
* [http://www.runnersworld.com/article/0,7120,s6-243-297--1102-0,00.html Could anandamide be the missing link to "runner's high"?] Accessed 2008-10-18


==References==
<references />
<br>


{{Cannabinoids}}
{{Cannabinoids}}
{{Neurotransmitters}}


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Revision as of 09:58, 27 October 2010

Template:Chembox E number
Anandamide
File:Anandamide skeletal.svg
Names
IUPAC name
(5Z,8Z,11Z,14Z)-N-(2-hydroxyethyl)icosa-5,8,11,14-tetraenamide
Other names
N-arachidonoylethanolamine
arachidonoylethanolamide
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value). Lua error in Module:Wikidata at line 879: attempt to index field 'wikibase' (a nil value).
MeSH Anandamide
Properties
C22H37NO2
Molar mass 347.53 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Anandamide, also known as N-arachidonoylethanolamine or AEA, is an endogenous cannabinoid neurotransmitter. It was isolated and its structure was first described 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.[1][2] It is synthesized from N-arachidonoyl phosphatidylethanolamine by multiple pathways.[3] 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.[4][5]

Physiological functions

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 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.

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.[citation needed]

Anandamide has been shown to be involved in working memory.[6] 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 pregnancy.[7] 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 levels.[8]

Anandamide also is important 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.[9]

A study published in 1998 shows that anandamide inhibits human breast cancer cell proliferation.[10]

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.

Synthesis and degradation

The human body synthesizes anandamide from N-arachidonoyl phosphatidylethanolamine (NAPE), which is itself made by transferring arachidonic acid from lecithin to the free amine of cephalin through an N-acyltransferase enzyme.[11][12] Anandamide synthesis from NarPE occurs via multiple pathways and includes enzymes such as phospholipase A2, phospholipase C and NAPE-PLD. [3]

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.[13] High fat diet feeding in mice increases levels of anandamide in the liver and increases lipogenesis.[14] This suggests that anandamide may play a role in the development of obesity, at least in rodents.

Paracetamol (or acetaminophen in the U.S.A.) is metabolically combined with arachidonic acid by FAAH to form AM404.[15] This metabolite of paracetamol is a potent agonist at the TRPV1 vanilloid receptor, a weak agonist at both CB1 and CB2 receptors, and an inhibitor of anandamide reuptake. As a result, anandamide levels in the body and brain are elevated. In this fashion, paracetamol acts as a pro-drug for a cannabimimetic metabolite. This action may be partially or fully responsible for the analgesic effects of paracetamol.[16][17]

See also

References

  1. ↑ Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992). "Isolation and structure of a brain constituent that binds to the cannabinoid receptor". Science. 258 (5090): 1946–9. doi:10.1126/science.1470919. PMID 1470919. Unknown parameter |month= ignored (help)
  2. ↑ Mechoulam R, Fride E (1995). "The unpaved road to the endogenous brain cannabinoid ligands, the anandamides". In Pertwee RG. Cannabinoid receptors. Boston: Academic Press. pp. 233–258. ISBN 0-12-551460-3.
  3. ↑ 3.0 3.1 Template:Cite doi
  4. ↑ Template:Cite doi
  5. ↑ Template:Cite doi
  6. ↑ allet PE, Beninger RJ (1996). "The endogenous cannabinoid receptor agonist anandamide impairs memory in rats". Behavioural Pharmacology. 7 (3): 276–284.
  7. ↑ Piomelli D (2004). "THC: moderation during implantation". Nat. Med. 10 (1): 19–20. doi:10.1038/nm0104-19. PMID 14702623. Unknown parameter |month= ignored (help)
  8. ↑ El-Talatini MR, Taylor AH, Konje JC (2010). "The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotrophins during the menstrual cycle". Fertil. Steril. 93 (6): 1989–96. doi:10.1016/j.fertnstert.2008.12.033. PMID 19200965. Unknown parameter |month= ignored (help)
  9. ↑ Mahler SV, Smith KS, Berridge KC (2007). "Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances 'liking' of a sweet reward". Neuropsychopharmacology. 32 (11): 2267–78. doi:10.1038/sj.npp.1301376. PMID 17406653. Unknown parameter |month= ignored (help)
  10. ↑ De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M, Di Marzo V (1998). "The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation". Proc. Natl. Acad. Sci. U.S.A. 95 (14): 8375–80. doi:10.1073/pnas.95.14.8375. PMC 20983. PMID 9653194. Unknown parameter |month= ignored (help)
  11. ↑ Natarajan V, Reddy PV, Schmid PC, Schmid HH (1982). "N-Acylation of ethanolamine phospholipids in canine myocardium". Biochim. Biophys. Acta. 712 (2): 342–55. PMID 7126608. Unknown parameter |month= ignored (help)
  12. ↑ Cadas H, di Tomaso E, Piomelli D (1997). "Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain". J. Neurosci. 17 (4): 1226–42. PMID 9006968. Unknown parameter |month= ignored (help)
  13. ↑ Berger A, Crozier G, Bisogno T, Cavaliere P, Innis S, Di Marzo V (2001). "Anandamide and diet: inclusion of dietary arachidonate and docosahexaenoate leads to increased brain levels of the corresponding N-acylethanolamines in piglets". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6402–6. doi:10.1073/pnas.101119098. PMC 33480. PMID 11353819. Unknown parameter |month= ignored (help)
  14. ↑ Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G (2005). "Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity". J. Clin. Invest. 115 (5): 1298–305. doi:10.1172/JCI23057. PMC 1087161. PMID 15864349. Unknown parameter |month= ignored (help)
  15. ↑ Template:Cite doi
  16. ↑ Bertolini A, Ferrari A, Ottani A, Guerzoni S, Tacchi R, Leone S (2006). "Paracetamol: new vistas of an old drug". CNS Drug Rev. 12 (3–4): 250–75. doi:10.1111/j.1527-3458.2006.00250.x. PMID 17227290.
  17. ↑ Sinning C, Watzer B, Coste O, Nüsing RM, Ott I, Ligresti A, Di Marzo V, Imming P (2008). "New analgesics synthetically derived from the paracetamol metabolite N-(4-hydroxyphenyl)-(5Z,8Z,11Z,14Z)-icosatetra-5,8,11,14-enamide". J. Med. Chem. 51 (24): 7800–5. doi:10.1021/jm800807k. PMID 19053765. Unknown parameter |month= ignored (help)

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