The Potential Use of Cannabidiol in the Treatment of Opioid Use Disorder: A Systematic Review.

Cannabidiol (CBD) has emerged as a potential treatment option for various psychiatric disorders, including substance use disorders. 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-reviewed 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-of-bias 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-tolerated profile during opioid use and withdrawal. Human clinical studies demonstrated a reduction in craving and alleviation of abstinence-induced anxiety. In preclinical studies, CBD has been shown to reduce withdrawal symptoms and diminish opioid-rewarding 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 'some concerns', while a notable level of 'unclear' 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-term follow-up, lack of combination therapy and heterogeneity across preclinical studies. TRIAL REGISTRATION: PROSPERO identifier: CRD42023401446.