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This study was aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous heroin withdrawal. Thirty hours after cessation of 8\u2010day heroin treatment (5, 10, 20 and 40\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\/12\u2009h; s.c.), spontaneous heroin withdrawal was evaluated in CD1 male mice. The effects of CBD (5, 10 and 20\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>; i.p.) on withdrawal\u2010related behaviour were evaluated by measuring anxiety\u2010like behaviour, motor activity and somatic signs. Furthermore, gene expression changes of mu\u2010opioid receptor (Oprm1), proopiomelanocortin (Pomc), cannabinoid CB1 (Cnr1) and CB2 (Cnr2) receptors in the nucleus accumbens (NAcc) and tyrosine hydroxylase (TH) and Pomc in the ventral tegmental area (VTA) were also evaluated by real\u2010time PCR. Anxiety\u2010like behaviour, motor activity and withdrawal\u2010related somatic signs were significantly increased in heroin\u2010treated mice compared to the control group. Interestingly, CBD treatment significantly reduced these behavioural impairments and normalized gene expression of Cnr1 and Pomc in the NAcc and TH in the VTA of mice exposed to spontaneous heroin withdrawal. Also, CBD induced an up\u2010regulation of Cnr2, whereas it did not change the increased gene expression of Oprm1 in the NAcc of abstinent animals. The results suggest that CBD alleviates spontaneous heroin withdrawal and normalizes the associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for the treatment of heroin withdrawal.<\/jats:p>","DOI":"10.1111\/adb.13150","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T08:59:20Z","timestamp":1644569960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["CBD\u2010mediated regulation of heroin withdrawal\u2010induced behavioural and molecular changes in mice"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1251-6357","authenticated-orcid":false,"given":"Francisco","family":"Navarrete","sequence":"first","affiliation":[{"name":"Instituto de Neurociencias Universidad Miguel Hern\u00e1ndez\u2010CSIC  Avda. de Ram\u00f3n y Cajal s\/n, San Juan de Alicante Alicante Spain"},{"name":"Redes de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS), Red de Investigaci\u00f3n en 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