Efficacy of cannabidiol alone or in combination with Delta-9-tetrahydrocannabinol for the management of substance use disorders: An umbrella review of the evidence.

Background And Aims: Substance use disorders (SUD) lead to a high burden of disease, yet treatment options are limited. Cannabidiol (CBD) is being investigated as a potential therapeutic target due to its pharmacological properties and mode of action in the endocannabinoid system. Recent systematic reviews (SR) on CBD and SUDs have shown inconsistent results. The objective of this umbrella review was to determine whether CBD alone or in combination with Delta-9-tetrahydrocannabinol (THC) is effective for managing and treating SUDs. Methods: Following a registered protocol, we searched PubMed, Web of Science and Epistemonikos databases for SRs, with or without a meta-analysis, of randomized controlled trials focusing on interventions dispensing CBD, alone or in combination with THC, to treat SUDs, published from 1 January 2000 to 15 October 2024. Screening, data extraction and quality assessment with the AMSTAR 2 tool were performed by two researchers in parallel and duplicated. Results: 22 SRs were included, 5 of which performed a meta-analysis. We found mixed evidence regarding the efficacy of CBD to manage and treat SUDs. Findings were interpreted in light of the quality of the SRs. Nabiximols, which contains CBD and THC, demonstrated positive effects on cannabis withdrawal and craving symptoms. Evidence supporting the efficacy of CBD is limited and inconclusive for abstinence, reduction or cessation of use of cannabis, tobacco, alcohol, opiates and other psychoactive substances. Conclusion: Cannabidiol (CBD) monotherapy does not appear to be efficacious for treatment of substance use disorders. CBD primarily exhibits effects on cannabis withdrawal and craving when combined with Delta-9-tetrahydrocannabinol (THC). Existing data on the efficacy of CBD alone with regard to other outcomes related to substance use disorders are limited.