{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:14:04Z","timestamp":1792271644410,"version":"4.4.0"},"reference-count":54,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2012,2]]},"DOI":"10.1124\/mol.111.074013","type":"journal-article","created":{"date-parts":[[2011,11,8]],"date-time":"2011-11-08T03:10:33Z","timestamp":1320721833000},"page":"250-263","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":149,"title":["Functional Selectivity in CB2 Cannabinoid Receptor Signaling and Regulation: Implications for the Therapeutic Potential of CB2 Ligands"],"prefix":"10.1016","volume":"81","author":[{"given":"Brady K.","family":"Atwood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Wager-Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Haskins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Straiker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Mackie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/mol.111.074013_bib1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.brainresrev.2008.12.003","article-title":"Targeting CB2 receptors and the endocannabinoid system for the treatment of pain","volume":"60","author":"Anand","year":"2009","journal-title":"Brain Res Rev"},{"key":"10.1124\/mol.111.074013_bib2","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1093\/emboj\/16.15.4606","article-title":"Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor","volume":"16","author":"Aramori","year":"1997","journal-title":"EMBO J"},{"key":"10.1124\/mol.111.074013_bib3","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1476-5381.2009.00582.x","article-title":"JWH018, a common constituent of \u2018Spice\u2019 herbal blends, is a potent and efficacious cannabinoid CB receptor agonist","volume":"160","author":"Atwood","year":"2010","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejphar.2011.01.066","article-title":"CP47,497-C8 and JWH073, commonly found in \u2018Spice\u2019 herbal blends, are potent and efficacious CB1 cannabinoid receptor agonists","volume":"659","author":"Atwood","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib5","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1476-5381.2010.00729.x","article-title":"CB2: a cannabinoid receptor with an identity crisis","volume":"160","author":"Atwood","year":"2010","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0014-5793(95)01207-U","article-title":"The peripheral cannabinoid receptor: adenylate cyclase inhibition and G protein coupling","volume":"375","author":"Bayewitch","year":"1995","journal-title":"FEBS Lett"},{"key":"10.1124\/mol.111.074013_bib7","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.1523\/JNEUROSCI.3923-04.2005","article-title":"A glial endogenous cannabinoid system is upregulated in the brains of macaques with simian immunodeficiency virus-induced encephalitis","volume":"25","author":"Benito","year":"2005","journal-title":"J Neurosci"},{"key":"10.1124\/mol.111.074013_bib8","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0009-3084(00)00195-X","article-title":"Cannabinoid receptors and the regulation of immune response","volume":"108","author":"Berdyshev","year":"2000","journal-title":"Chem Phys Lipids"},{"key":"10.1124\/mol.111.074013_bib9","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/sj.bjp.0707303","article-title":"Species-specific in vitro pharmacological effects of the cannabinoid receptor 2 (CB2) selective ligand AM1241 and its resolved enantiomers","volume":"151","author":"Bingham","year":"2007","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib10","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.chembiol.2007.11.006","article-title":"A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol","volume":"14","author":"Blankman","year":"2007","journal-title":"Chem Biol"},{"key":"10.1124\/mol.111.074013_bib11","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1476-5381.2010.00756.x","article-title":"The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice","volume":"160","author":"Bolognini","year":"2010","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib12","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. Implications for receptor biological responses","volume":"274","author":"Bouaboula","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.111.074013_bib13","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0167-4781(02)00341-X","article-title":"Cloning and molecular characterization of the rat CB2 cannabinoid receptor","volume":"1576","author":"Brown","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"10.1124\/mol.111.074013_bib14","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.1017\/S1462399409000957","article-title":"Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation","volume":"11","author":"Cabral","year":"2009","journal-title":"Expert Rev Mol Med"},{"key":"10.1124\/mol.111.074013_bib15","doi-asserted-by":"crossref","first-page":"9371","DOI":"10.1073\/pnas.161191698","article-title":"Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase","volume":"98","author":"Cravatt","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.111.074013_bib16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neuropharm.2007.06.005","article-title":"Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1\/2 MAP kinase signaling","volume":"54","author":"Daigle","year":"2008","journal-title":"Neuropharmacology"},{"key":"10.1124\/mol.111.074013_bib17","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0026-895X(25)10492-6","article-title":"Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors","volume":"48","author":"Felder","year":"1995","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.111.074013_bib18","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0896-6273(01)00517-7","article-title":"Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal","volume":"32","author":"Finn","year":"2001","journal-title":"Neuron"},{"key":"10.1124\/mol.111.074013_bib19","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1016\/0960-894X(96)00426-X","article-title":"New class of potent ligands for the human peripheral cannabinoid receptor","volume":"6","author":"Gallant","year":"1996","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1124\/mol.111.074013_bib20","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/S0022-3565(24)35367-4","article-title":"Cloning and pharmacological characterization of the rat CB(2) cannabinoid receptor","volume":"292","author":"Griffin","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.111.074013_bib21","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1016\/j.bbamcr.2011.05.010","article-title":"Cannabinoid receptor 2 undergoes Rab5-mediated internalization and recycles via a Rab11-dependent pathway","volume":"1813","author":"Grimsey","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"10.1124\/mol.111.074013_bib22","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology. XXVII. Classification of cannabinoid receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol Rev"},{"key":"10.1124\/mol.111.074013_bib23","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1046\/j.1471-4159.1999.0730493.x","article-title":"Internalization and recycling of the CB1 cannabinoid receptor","volume":"73","author":"Hsieh","year":"1999","journal-title":"J Neurochem"},{"key":"10.1124\/mol.111.074013_bib24","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1001\/archpsyc.58.4.322","article-title":"Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716","volume":"58","author":"Huestis","year":"2001","journal-title":"Arch Gen Psychiatry"},{"key":"10.1124\/mol.111.074013_bib25","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0960-894X(01)80155-4","article-title":"Design, Synthesis and Pharmacology of Cannabimimetic Indoles","volume":"4","author":"Huffman","year":"1994","journal-title":"Bioorganic & Medicinal Chemistry Letters"},{"key":"10.1124\/mol.111.074013_bib26","doi-asserted-by":"crossref","first-page":"10529","DOI":"10.1073\/pnas.1834309100","article-title":"Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS","volume":"100","author":"Ibrahim","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.111.074013_bib27","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1124\/mol.104.006882","article-title":"Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors enhances heterodimer formation: a mechanism for receptor cross-talk?","volume":"67","author":"Kearn","year":"2005","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.111.074013_bib28","doi-asserted-by":"crossref","first-page":"6493","DOI":"10.1021\/jm070441u","article-title":"Cannabilactones: a novel class of CB2 selective agonists with peripheral analgesic activity","volume":"50","author":"Khanolkar","year":"2007","journal-title":"J Med Chem"},{"key":"10.1124\/mol.111.074013_bib29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.pharmthera.2007.10.003","article-title":"Role of receptor internalization in opioid tolerance and dependence","volume":"117","author":"Koch","year":"2008","journal-title":"Pharmacol Ther"},{"key":"10.1124\/mol.111.074013_bib30","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1124\/mol.104.004994","article-title":"Receptor endocytosis counteracts the development of opioid tolerance","volume":"67","author":"Koch","year":"2005","journal-title":"Mol Pharmacol"},{"key":"10.1124\/mol.111.074013_bib31","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2174\/156800705774933104","article-title":"Endocannabinoid metabolic pathways and enzymes","volume":"4","author":"Ligresti","year":"2005","journal-title":"Curr Drug Targets CNS Neurol Disord"},{"key":"10.1124\/mol.111.074013_bib32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nchembio.129","article-title":"Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects","volume":"5","author":"Long","year":"2009","journal-title":"Nat Chem Biol"},{"key":"10.1124\/mol.111.074013_bib33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/3-540-26573-2_10","article-title":"Distribution of cannabinoid receptors in the central and peripheral nervous system","volume":"168","author":"Mackie","year":"2005","journal-title":"Handb Exp Pharmacol"},{"key":"10.1124\/mol.111.074013_bib34","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/sj.bjp.0707523","article-title":"CB2 receptor-mediated migration of immune cells: it can go either way","volume":"153","author":"Miller","year":"2008","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib35","doi-asserted-by":"crossref","first-page":"e269","DOI":"10.1371\/journal.pbio.0050269","article-title":"Genetic dissection of behavioural and autonomic effects of Delta(9)-tetrahydrocannabinol in mice","volume":"5","author":"Monory","year":"2007","journal-title":"PLoS Biol"},{"key":"10.1124\/mol.111.074013_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejphar.2004.09.058","article-title":"Species comparison and pharmacological characterization of rat and human CB2 cannabinoid receptors","volume":"505","author":"Mukherjee","year":"2004","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib37","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.tips.2011.06.008","article-title":"The delta opioid receptor: an evolving target for the treatment of brain disorders","volume":"32","author":"Pradhan","year":"2011","journal-title":"Trends Pharmacol Sci"},{"key":"10.1124\/mol.111.074013_bib38","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.pbb.2011.02.024","article-title":"Pharmacological characterization of AM1710, a putative cannabinoid CB2 agonist from the cannabilactone class: antinociception without central nervous system side-effects","volume":"98","author":"Rahn","year":"2011","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1124\/mol.111.074013_bib39","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrd3024","article-title":"Teaching old receptors new tricks: biasing seven-transmembrane receptors","volume":"9","author":"Rajagopal","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"10.1124\/mol.111.074013_bib40","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1038\/sj.bjp.0702351","article-title":"Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656, and AM630","volume":"126","author":"Ross","year":"1999","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib41","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0028-3908(00)00135-0","article-title":"Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception","volume":"40","author":"Ross","year":"2001","journal-title":"Neuropharmacology"},{"key":"10.1124\/mol.111.074013_bib42","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.chembiol.2011.05.012","article-title":"Mechanisms of osteoclastogenesis inhibition by a novel class of biphenyl-type cannabinoid CB(2) receptor inverse agonists","volume":"18","author":"Schuehly","year":"2011","journal-title":"Chem Biol"},{"key":"10.1124\/mol.111.074013_bib43","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1124\/jpet.105.089474","article-title":"Agonist-directed trafficking of response by endocannabinoids acting at CB2 receptors","volume":"315","author":"Shoemaker","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.111.074013_bib44","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0022-3565(24)37469-5","article-title":"Mutation of a highly conserved aspartate residue in the second transmembrane domain of the cannabinoid receptors, CB1 and CB2, disrupts G-protein coupling","volume":"285","author":"Tao","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.111.074013_bib45","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/sj.bjp.0706414","article-title":"Evidence that the plant cannabinoid Delta9-tetrahydrocannabivarin is a cannabinoid CB1 and CB2 receptor antagonist","volume":"146","author":"Thomas","year":"2005","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.111.074013_bib46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/jpet.106.104463","article-title":"Functional selectivity and classical concepts of quantitative pharmacology","volume":"320","author":"Urban","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.111.074013_bib47","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S0959-4388(03)00069-2","article-title":"Regulated endocytosis of opioid receptors: cellular mechanisms and proposed roles in physiological adaptation to opiate drugs","volume":"13","author":"von Zastrow","year":"2003","journal-title":"Curr Opin Neurobiol"},{"key":"10.1124\/mol.111.074013_bib48","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S0896-6273(01)80032-5","article-title":"Functional dissociation of mu opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction","volume":"23","author":"Whistler","year":"1999","journal-title":"Neuron"},{"key":"10.1124\/mol.111.074013_bib49","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.neuroscience.2005.06.009","article-title":"Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons","volume":"135","author":"Wotherspoon","year":"2005","journal-title":"Neuroscience"},{"key":"10.1124\/mol.111.074013_bib50","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1471-4159.2007.05063.x","article-title":"Role of receptor internalization in the agonist-induced desensitization of cannabinoid type 1 receptors","volume":"104","author":"Wu","year":"2008","journal-title":"J Neurochem"},{"key":"10.1124\/mol.111.074013_bib51","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/nn.2874","article-title":"Brain cannabinoid CB(2) receptors modulate cocaine\u2019s actions in mice","volume":"14","author":"Xi","year":"2011","journal-title":"Nat Neurosci"},{"key":"10.1124\/mol.111.074013_bib52","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1124\/jpet.108.145011","volume":"328","author":"Yao","year":"2009","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.111.074013_bib53","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1471-2377-6-12","article-title":"COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells\/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord","volume":"6","author":"Yiangou","year":"2006","journal-title":"BMC Neurol"},{"key":"10.1124\/mol.111.074013_bib54","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1046\/j.1460-9568.2003.02704.x","article-title":"Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models","volume":"17","author":"Zhang","year":"2003","journal-title":"Eur J Neurosci"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24033959?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24033959?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/mol.111.074013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:40:51Z","timestamp":1739943651000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24033959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2]]},"references-count":54,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,2]]}},"alternative-id":["S0026895X24033959"],"URL":"https:\/\/doi.org\/10.1124\/mol.111.074013","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2012,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Functional Selectivity in CB2 Cannabinoid Receptor Signaling and Regulation: Implications for the Therapeutic Potential of CB2 Ligands","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/mol.111.074013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2012 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}