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This systematic review is aimed at reviewing the evidence regarding the safety and efficacy of CBD as a therapeutic option in opioid use disorder (OUD) treatment in clinical and preclinical studies. We searched MEDLINE, Embase, PsycINFO, Scopus, Web of Science, CDSR and CENTRAL up to December 2023. We included original peer\u2010reviewed human and animal studies evaluating CBD for OUD outcomes and excluded those that did not report OUD outcomes or used CBD solely with THC. The risk of bias was assessed with the Cochrane risk\u2010of\u2010bias tool for human studies and SYRCLE's tool for animal studies. Due to outcome heterogeneity, findings were presented using a qualitative synthesis. Four clinical studies (74 participants) and 16 preclinical studies met the inclusion criteria. The collective evidence from clinical and preclinical studies indicates that CBD holds promise as an adjunctive therapy for OUD with a well\u2010tolerated profile during opioid use and withdrawal. Human clinical studies demonstrated a reduction in craving and alleviation of abstinence\u2010induced anxiety. In preclinical studies, CBD has been shown to reduce withdrawal symptoms and diminish opioid\u2010rewarding effects using the conditioned place preference paradigm, although the results are mixed, and not all preclinical studies reported these effects. The quality assessment for clinical studies indicated an overall evaluation of \u2018some concerns\u2019, while a notable level of \u2018unclear\u2019 risk was observed across the evaluated domains for preclinical studies. This systematic review highlights the potential of CBD as a beneficial treatment option for addressing cravings and anxiety symptoms during abstinence in individuals with OUD, based on findings from human studies. Continued research and clinical trials will be essential for further improving outcomes in OUD treatment using novel effective treatment approaches. Study limitations include the limited number of clinical studies, small sample size, short\u2010term follow\u2010up, lack of combination therapy and heterogeneity across preclinical studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>PROSPERO identifier: CRD42023401446<\/jats:p><\/jats:sec>","DOI":"10.1111\/adb.70047","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T06:04:19Z","timestamp":1748239459000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Potential Use of Cannabidiol in the Treatment of Opioid Use Disorder: A Systematic Review"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-0374","authenticated-orcid":false,"given":"Mahan","family":"Shafie","sequence":"first","affiliation":[{"name":"School of Medicine Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Ing","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California San Diego  La Jolla California USA"},{"name":"VA San Diego Healthcare System  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasna","family":"Rostam\u2010Abadi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Weleff","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Psychiatry, Faculty of Medicine &amp; Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Neuroscience and Mental Health Institute University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohini","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA Connecticut Healthcare System  West Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardavan","family":"Mohammad\u00a0Aghaei","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Pratt","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa\u00a0C.","family":"Funaro","sequence":"additional","affiliation":[{"name":"Harvey Cushing\/John Hay Whitney Medical Library Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anahita","family":"Bassir\u00a0Nia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA Connecticut Healthcare System  West Haven Connecticut USA"},{"name":"Clinical Neurosciences Division National Center for PTSD (NCPTD), VA Connecticut Healthcare System  West Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajp.2023.103677"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.108350"},{"key":"e_1_2_12_4_1","unstructured":"J. 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