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The purpose of this review was to determine the functional involvement of CB2r in the effects produced by drugs of abuse at the central nervous system (CNS) level by assessing evidence from preclinical and clinical studies. In rodents, several reports suggest the functional involvement of CB2r in the effects produced by drugs of abuse such as alcohol, cocaine, or nicotine. In addition, the discovery of CB2r in brain areas that are part of the reward system supports the relevance of CB2r in the field of addiction. Interestingly, animal studies support that the CB2r regulates anxiety and depression behavioral traits. Due to its frequent comorbidity with neuropsychiatric disorders, these pharmacological actions may be of great interest in managing SUD. Preliminary clinical trials are focused on exploring the therapeutic potential of modulating CB2r in treating addictive disorders. These promising results support the development of new pharmacological tools regulating the CB2r that may help to increase the therapeutic success in the management of SUD.<\/jats:p>","DOI":"10.3390\/biom11111556","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:29:46Z","timestamp":1634765386000},"page":"1556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["CB2 Receptor Involvement in the Treatment of Substance Use Disorders"],"prefix":"10.3390","volume":"11","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-CSIC, Avda. de Ram\u00f3n y Cajal s\/n, San Juan de Alicante, 03550 Alicante, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda S.","family":"Garc\u00eda-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC, Avda. de Ram\u00f3n y Cajal s\/n, San Juan de Alicante, 03550 Alicante, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9646-9975","authenticated-orcid":false,"given":"Ani","family":"Gasparyan","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC, Avda. de Ram\u00f3n y Cajal s\/n, San Juan de Alicante, 03550 Alicante, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Navarro","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC, Avda. de Ram\u00f3n y Cajal s\/n, San Juan de Alicante, 03550 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4681-1533","authenticated-orcid":false,"given":"Jorge","family":"Manzanares","sequence":"additional","affiliation":[{"name":"Instituto de Neurociencias, Universidad Miguel Hern\u00e1ndez-CSIC, Avda. de Ram\u00f3n y Cajal s\/n, San Juan de Alicante, 03550 Alicante, Spain"},{"name":"Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Salud (RETICS), Red de Trastornos Adictivos, Instituto de Salud Carlos III, MICINN and FEDER, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"APA (2014). 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