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Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials

dc.rights.licenseopenen_US
dc.contributor.authorHANEY, Margaret
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorVALLÉE, Monique
dc.contributor.authorFABRE, Sandy
dc.contributor.authorCOLLINS REED, Stephanie
dc.contributor.authorZANESE, Marion
dc.contributor.authorCAMPISTRON, Ghislaine
dc.contributor.authorAROUT, Caroline A
dc.contributor.authorFOLTIN, Richard W
dc.contributor.authorCOOPER, Ziva D
dc.contributor.authorKEARNEY-RAMOS, Tonisha
dc.contributor.authorMETNA, Mathilde
dc.contributor.authorJUSTINOVA, Zuzana
dc.contributor.authorSCHINDLER, Charles
dc.contributor.authorHEBERT-CHATELAIN, Etienne
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBELLOCCHIO, Luigi
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCATHALA, Adeline
dc.contributor.authorBARI, Andrea
dc.contributor.authorSERRAT, Roman
dc.contributor.authorFINLAY, David B
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCARACI, Filippo
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorREDON, Bastien
dc.contributor.authorMARTÍN-GARCÍA, Elena
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorBUSQUETS-GARCIA, Arnau
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMATIAS, Isabelle
dc.contributor.authorLEVIN, Frances R
dc.contributor.authorFELPIN, François-Xavier
dc.contributor.authorSIMON, Nicolas
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCOTA, Daniela
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorSPAMPINATO, Umberto
dc.contributor.authorMALDONADO, Rafael
dc.contributor.authorSHAHAM, Yavin
dc.contributor.authorGLASS, Michelle
dc.contributor.authorTHOMSEN, Lars Lykke
dc.contributor.authorMENGEL, Helle
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorMARSICANO, Giovanni
dc.contributor.authorMONLEZUN, Stéphanie
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorREVEST, Jean-Michel
dc.contributor.authorPIAZZA, Pier Vincenzo
dc.date.accessioned2024-01-08T14:40:49Z
dc.date.available2024-01-08T14:40:49Z
dc.date.issued2023-06-01
dc.identifier.issn1546-170Xen_US
dc.identifier.otherhttps://doi.org/10.1038/ s41591-023-02381-w.en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/186944
dc.description.abstractEnCannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice and non-human primates, AEF0117 decreased cannabinoid self-administration and THC-related behavioral impairment without producing significant adverse effects. In single-ascending-dose (0.2 mg, 0.6 mg, 2 mg and 6 mg; n = 40) and multiple-ascending-dose (0.6 mg, 2 mg and 6 mg; n = 24) phase 1 trials, healthy volunteers were randomized to ascending-dose cohorts (n = 8 per cohort; 6:2 AEF0117 to placebo randomization). In both studies, AEF0117 was safe and well tolerated (primary outcome measurements). In a double-blind, placebo-controlled, crossover phase 2a trial, volunteers with CUD were randomized to two ascending-dose cohorts (0.06 mg, n = 14; 1 mg, n = 15). AEF0117 significantly reduced cannabis' positive subjective effects (primary outcome measurement, assessed by visual analog scales) by 19% (0.06 mg) and 38% (1 mg) compared to placebo (P < 0.04). AEF0117 (1 mg) also reduced cannabis self-administration (P < 0.05). In volunteers with CUD, AEF0117 was well tolerated and did not precipitate cannabis withdrawal. These data suggest that AEF0117 is a safe and potentially efficacious treatment for CUD.ClinicalTrials.gov identifiers: NCT03325595 , NCT03443895 and NCT03717272 .
dc.description.sponsorshipBordeaux Region Aquitaine Initiative for Neuroscienceen_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enAnimals
dc.subject.enMice
dc.subject.enCannabis
dc.subject.enDouble-Blind Method
dc.subject.enDronabinol
dc.subject.enHallucinogens
dc.subject.enMarijuana Abuse
dc.subject.enRandomized Controlled Trials as Topic
dc.subject.enSubstance Withdrawal Syndrome
dc.title.enSignaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials
dc.title.alternativeNat Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41591-023-02381-w.en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed37291212en_US
bordeaux.journalNature Medicineen_US
bordeaux.page1487-1499en_US
bordeaux.volume29en_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.issue6en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.institutionINSERMen_US
bordeaux.teamEndocannabinoïdes et Neuroadaptationen_US
bordeaux.teamPhysiopathologie de l'équilibre énergétique et obésitéen_US
bordeaux.teamPhysiopathologie et approches thérapeutiques des maladies liées au stressen_US
bordeaux.teamChimie analytiqueen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDMission Interministérielle de Lutte Contre les Drogues et les Conduites Addictivesen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.identifier.funderIDMinisterio de Sanidad, Servicios Sociales e Igualdaden_US
bordeaux.identifier.funderIDPlan Nacional sobre Drogasen_US
bordeaux.import.sourcepubmed
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcepubmed
dc.rights.ccCC BYen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Nature%20Medicine&amp;rft.date=2023-06-01&amp;rft.volume=29&amp;rft.issue=6&amp;rft.spage=1487-1499&amp;rft.epage=1487-1499&amp;rft.eissn=1546-170X&amp;rft.issn=1546-170X&amp;rft.au=HANEY,%20Margaret&amp;VALL%C3%89E,%20Monique&amp;FABRE,%20Sandy&amp;COLLINS%20REED,%20Stephanie&amp;ZANESE,%20Marion&amp;rft.genre=article


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