A roadmap to finding the best treatments for cannabis use disorder

Cannabis use disorder (CUD) imposes a significant global health burden, yet comparative evidence for the diverse range of non-pharmacological interventions (NPIs) remains fragmented. Existing reviews often combine diverse NPIs into broad categories, overlooking the specific contributions of neurobiological modalities. This study aims to establish a comprehensive comparative efficacy hierarchy for non-pharmacological CUD interventions by integrating psychosocial therapies and neurotherapy into a unified analytical framework. We will conduct a systematic review and network meta-analysis (NMA) of randomized controlled trials comparing NPIs against control group(including waitlist, no-intervention, or non-specific control) or another NPIs for individuals with CUD. Systematic searches will be performed across PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). Primary benefit outcomes will include biochemically verified cannabis abstinenc and self-reported days of cannabis use over the past 30 days. Primary acceptability will be evaluated by treatment retention, defined using an intention-to-treat approach as the proportion of randomized participants completing at least one session during the final treatment week, alongside follow-up retention rates. Primary safety will be assessed by the overall incidence of intervention-related adverse and serious adverse events. Pairs of reviewers will independently perform study selection, data extraction, and risk of bias. A frequentist NMA will be conducted to synthesize evidence. We will employ the Grading of Recommendations Assessment, Development and Evaluations(GRADE) approach to assess the certainty of evidence and categorize interventions using a minimally contextualized framework based on predefined decision thresholds. Comprehensive search strategies have been validated across target databases. Formal study screening, data extraction, quantitative network meta-analyses, and GRADE evidence assessments are scheduled for completion by September 2026, followed by final manuscript preparation. This NMA will establish a comprehensive comparative evidence hierarchy for non-pharmacological CUD interventions by bridging psychosocial and neurobiological modalities. By pairing network estimates with GRADE certainty assessments, our findings will offer a standardized, actionable foundation for tailored clinical care and future trial methodology. PROSPERO CRD420251173215.