{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:03:52Z","timestamp":1767855832807,"version":"3.49.0"},"reference-count":61,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Trends in Pharmacological Sciences"],"published-print":{"date-parts":[[2000,6]]},"DOI":"10.1016\/s0165-6147(00)01482-6","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T02:48:57Z","timestamp":1027651737000},"page":"218-224","source":"Crossref","is-referenced-by-count":336,"title":["The endocannabinoid system as a target for therapeutic drugs"],"prefix":"10.1016","volume":"21","author":[{"given":"Daniele","family":"Piomelli","sequence":"first","affiliation":[]},{"given":"Andrea","family":"Giuffrida","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"Calignano","sequence":"additional","affiliation":[]},{"given":"Fernando","family":"Rodr\u0131\u0301guez de Fonseca","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/S0165-6147(00)01482-6_BIB1","first-page":"605","article-title":"Determination and characterization of a cannabinoid receptor in rat brain","volume":"34","author":"Devane","year":"1988","journal-title":"Mol. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/346561a0","article-title":"Structure of a cannabinoid receptor and functional expression of the cloned cDNA","volume":"346","author":"Matsuda","year":"1990","journal-title":"Nature"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB3","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1126\/science.1470919","article-title":"Isolation and structure of a brain constituent that binds to the cannabinoid receptor","volume":"258","author":"Devane","year":"1992","journal-title":"Science"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1006\/bbrc.1995.2437","article-title":"2-arachidonoylglycerol","volume":"215","author":"Sugiura","year":"1995","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0006-2952(95)00109-D","article-title":"Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors","volume":"50","author":"Mechoulam","year":"1995","journal-title":"Biochem. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB6","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1006\/nbdi.1998.0221","article-title":"Endogenous cannabinoid signaling","volume":"5","author":"Piomelli","year":"1998","journal-title":"Neurobiol. Dis"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB7","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/7268","article-title":"Dopamine activation of endogenous cannabinoid signaling in dorsal striatum","volume":"2","author":"Giuffrida","year":"1999","journal-title":"Nat. Neurosci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB8","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1126\/science.277.5329.1094","article-title":"Functional role of high-affinity anandamide transport, as revealed by selective inhibition","volume":"277","author":"Beltramo","year":"1997","journal-title":"Science"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB9","doi-asserted-by":"crossref","first-page":"5802","DOI":"10.1073\/pnas.96.10.5802","article-title":"Structural determinants for recognition and translocation by the anandamide transporter","volume":"96","author":"Piomelli","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB10","doi-asserted-by":"crossref","first-page":"14145","DOI":"10.1016\/S0021-9258(17)38695-7","article-title":"Properties of rat liver N-acylethanolamine amidohydrolase","volume":"260","author":"Schmid","year":"1985","journal-title":"J. Biol. Chem"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/384083a0","article-title":"Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides","volume":"384","author":"Cravatt","year":"1996","journal-title":"Nature"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB12","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/42015","article-title":"A second endogenous cannabinoid that modulates long-term potentiation","volume":"388","author":"Stella","year":"1997","journal-title":"Nature"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB13","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/S0014-2999(98)00777-8","article-title":"Carbachol, an acetylcholine receptor agonist, enhances production in rat aorta of 2-arachidonoyl glycerol, a hypotensive endocannabinoid","volume":"362","author":"Mechoulam","year":"1998","journal-title":"Eur. J. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB14","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0006-2952(98)00314-1","article-title":"Enzymes of porcine brain hydrolysing 2-arachidonylglycerol, an endogenous ligand of cannabinoid receptors","volume":"57","author":"Goparaju","year":"1999","journal-title":"Biochem. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB15","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1523\/JNEUROSCI.20-09-03401.2000","article-title":"Reversal of dopamine D2-receptor responses by an anandamide transport inhibitor","volume":"20","author":"Beltramo","year":"2000","journal-title":"J. Neurosci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB16","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/S0014-2999(97)01297-1","article-title":"Potentiation of anandamide hypotension by the transport inhibitor, AM404","volume":"337","author":"Calignano","year":"1997","journal-title":"Eur. J. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB17","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0024-3205(99)00251-9","article-title":"Extrapyramidal and neuroendocrine effects of AM404, an inhibitor of the carrier-mediated transport of anandamide","volume":"65","author":"Gonzalez","year":"1999","journal-title":"Life Sci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB18","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0024-3205(99)00283-0","article-title":"Structure\u2013activity relationships of anandamide, an endogenous cannabinoid ligand","volume":"65","author":"Khanolkar","year":"1999","journal-title":"Life Sci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB19","unstructured":"Salamone, J. et al. (2000) 6th Internet World Congress for Biomedical Sciences (http:\/\/www.uclm.es\/inabis2000\/symposia\/files\/119\/ index.htm)"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB20","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular characterization of a peripheral receptor for cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0163-7258(97)82001-3","article-title":"Pharmacology of cannabinoid CB1 and CB2 receptors","volume":"74","author":"Pertwee","year":"1997","journal-title":"Pharmacol. Ther"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB22","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1523\/JNEUROSCI.19-10-03773.1999","article-title":"Distinct domains of the CB1 cannabinoid receptor mediate desensitization and internalization","volume":"19","author":"Jin","year":"1999","journal-title":"J. Neurosci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB23","doi-asserted-by":"crossref","first-page":"20397","DOI":"10.1074\/jbc.274.29.20397","article-title":"Regulation of peripheral cannabinoid receptor CB2 phosphorylation by the inverse agonist SR 144528","volume":"274","author":"Bouaboula","year":"1999","journal-title":"J. Biol. Chem"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB24","first-page":"478","article-title":"Large receptor reserve for cannabinoid actions in the central nervous system","volume":"288","author":"Gifford","year":"1999","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB25","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0167-5699(98)01300-0","article-title":"Cannabinoid receptors and immunity","volume":"19","author":"Klein","year":"1998","journal-title":"Immunol. Today"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB26","doi-asserted-by":"crossref","first-page":"14136","DOI":"10.1073\/pnas.96.24.14136","article-title":"Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors","volume":"96","author":"J\u00e1rai","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0165-6147(99)01430-3","article-title":"Anandamide \u2013 the other side of the coin","volume":"21","author":"Zygmunt","year":"2000","journal-title":"Trends Pharmacol. Sci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB28","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0165-6147(99)01436-4","article-title":"Are cannabinoids endogenous ligands for the VR1 capsaicin receptor?","volume":"21","author":"Szolcs\u00e1nyi","year":"2000","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/S0165-6147(00)01482-6_BIB29","unstructured":"Joy J.E. et al., (Eds.) (1999) Marijuana and Medicine: Assessing the ScienceBase,National Academy Press"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB30","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0006-8993(98)01368-7","article-title":"Anatomical basis for cannabinoid-induced antinociception as revealed by intracerebral microinjections","volume":"822","author":"Martin","year":"1999","journal-title":"Brain Res"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0006-8993(98)01321-3","article-title":"Pre- and postsynaptic distribution of cannabinoid and mu opioid receptors in rat spinal cord","volume":"822","author":"Hohmann","year":"1999","journal-title":"Brain Res"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB32","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0306-4522(98)00524-7","article-title":"Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a double-label in situ hybridization study","volume":"90","author":"Hohmann","year":"1999","journal-title":"Neuroscience"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB33","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1523\/JNEUROSCI.18-01-00451.1998","article-title":"Hypoactivity of the spinal cannabinoid system results in NMDA-dependent hyperalgesia","volume":"18","author":"Richardson","year":"1998","journal-title":"J. Neurosci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB34","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/S0306-4522(99)00220-1","article-title":"Cannabinoid receptors undergo axonal flow in sensory nerves","volume":"92","author":"Hohmann","year":"1999","journal-title":"Neuroscience"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB35","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/28393","article-title":"Control of pain initiation by endogenous cannabinoids","volume":"394","author":"Calignano","year":"1998","journal-title":"Nature"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB36","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0304-3959(97)00213-3","article-title":"Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral CB1 receptors","volume":"75","author":"Richardson","year":"1998","journal-title":"Pain"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1006\/nbdi.1998.0218","article-title":"Cannabinoid transmission and pain perception","volume":"5","author":"Martin","year":"1998","journal-title":"Neurobiol. Dis"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB38","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S0140-6736(98)05429-4","article-title":"Analgesic effects of the cannabinoid analogue nabilone is not mediated by opioid receptors","volume":"353","author":"Hamann","year":"1999","journal-title":"Lancet"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB39","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0304-3940(96)13308-5","article-title":"The analgesic effects of R(1)-Win 55,212-2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain","volume":"221","author":"Herzberg","year":"1997","journal-title":"Neurosci. Lett"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB40","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0304-3959(98)00263-2","article-title":"The cannabinoid receptor agonist WIN 55,212-2 mesylate blocks the development of hyperalgesia produced by capsaicin in rats","volume":"81","author":"Li","year":"1999","journal-title":"Pain"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB41","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0304-3959(99)00045-7","article-title":"Spinal cannabinoids are anti-allodynic in rats with persistent inflammation","volume":"82","author":"Martin","year":"1999","journal-title":"Pain"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB42","doi-asserted-by":"crossref","first-page":"12198","DOI":"10.1073\/pnas.96.21.12198","article-title":"Pain modulation by release of the endogenous cannabinoid anandamide","volume":"96","author":"Walker","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB43","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJM199506223322506","article-title":"The control of pain in peripheral tissue by opioids","volume":"332","author":"Stein","year":"1995","journal-title":"New Engl. J. Med"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB44","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1016\/0014-2999(94)90666-1","article-title":"The action of synthetic cannabinoids on the induction of long-term potentiation in the rat hippocampal slice","volume":"259","author":"Collins","year":"1994","journal-title":"Eur. J. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB45","doi-asserted-by":"crossref","first-page":"A7","DOI":"10.1038\/399a007","article-title":"The changing landscape of ischaemic brain injury mechanisms","volume":"399","author":"Lee","year":"1999","journal-title":"Nature"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB46","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1124\/mol.54.3.459","article-title":"Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity","volume":"54","author":"Shen","year":"1998","journal-title":"Mol. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB47","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1523\/JNEUROSCI.19-08-02987.1999","article-title":"Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures","volume":"19","author":"Nagayama","year":"1999","journal-title":"J. Neurosci"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB48","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/(SICI)1098-2396(199810)30:2<221::AID-SYN12>3.0.CO;2-4","article-title":"Effects of intrastriatal cannabinoid on rotational behavior in rats","volume":"30","author":"Sa\u00f1udo-Pe\u00f1a","year":"1998","journal-title":"Synapse"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB49","doi-asserted-by":"crossref","first-page":"5780","DOI":"10.1073\/pnas.96.10.5780","article-title":"Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice","volume":"96","author":"Zimmer","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB50","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/mds.870130603","article-title":"Adjuncts to dopamine replacement","volume":"13","author":"Brotchie","year":"1998","journal-title":"Mov. Disord"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB51","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1176\/ajp.156.3.495","article-title":"Treatment of Tourette-Syndrome with \u0394-9\u2013tetrahydrocannabinol","volume":"156","author":"M\u00fcller-Vahl","year":"1999","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB52","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/S0140-6736(87)92620-1","article-title":"Cannabis and schizophrenia","volume":"2","author":"Andr\u00e9asson","year":"1987","journal-title":"Lancet"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB53","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0014-2999(98)00851-6","article-title":"Chronic (\u2212)-\u03949-tetrahydrocannabinol treatment induces sensitization to the psychomotor effects of amphetamine in rats","volume":"365","author":"Gorriti","year":"1999","journal-title":"Eur. J. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB54","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1146\/annurev.pa.35.040195.003135","article-title":"Pharmacology of cannabinoid receptors","volume":"35","author":"Howlett","year":"1995","journal-title":"Annu. Rev. Pharmacol. Toxicol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB55","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1021\/jm00038a020","article-title":"(R)-Methanandamide: a chiral novel anandamide possessing higher potency and metabolic stability","volume":"37","author":"Abadji","year":"1994","journal-title":"J. Med. Chem."},{"key":"10.1016\/S0165-6147(00)01482-6_BIB56","first-page":"989","article-title":"Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2)","volume":"278","author":"Showalter","year":"1996","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB57","first-page":"1427","article-title":"Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1)","volume":"289","author":"Hillard","year":"1999","journal-title":"J. Pharmacol. Exp. Ther"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB58","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/sj.bjp.0702351","article-title":"Agonist-inverse characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630","volume":"12","author":"Ross","year":"1999","journal-title":"Br. J. Pharmacol"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB59","doi-asserted-by":"crossref","first-page":"14228","DOI":"10.1073\/pnas.96.25.14228","article-title":"HU-308","volume":"96","author":"Hanus","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB60","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/0014-5793(94)00773-X","article-title":"SR141716A, a potent and selective antagonist of the brain cannabinoid receptor","volume":"350","author":"Rinaldi-Carmona","year":"1994","journal-title":"FEBS Lett"},{"key":"10.1016\/S0165-6147(00)01482-6_BIB61","first-page":"644","article-title":"SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor","volume":"284","author":"Rinaldi-Carmona","year":"1998","journal-title":"J. Pharmacol. Exp. Ther"}],"container-title":["Trends in Pharmacological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165614700014826?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0165614700014826?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T12:47:29Z","timestamp":1681735649000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0165614700014826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,6]]},"references-count":61,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2000,6]]}},"alternative-id":["S0165614700014826"],"URL":"https:\/\/doi.org\/10.1016\/s0165-6147(00)01482-6","relation":{},"ISSN":["0165-6147"],"issn-type":[{"value":"0165-6147","type":"print"}],"subject":[],"published":{"date-parts":[[2000,6]]}}}