INTRODUCTION: Substance use disorder (SUD) is a major global health issue, contributing significantly to the disease burden. Despite this, effective treatments for SUD remain limited. Ketamine has shown potential as a treatment, yet no meta-analysis has assessed its efficacy for SUD. This study aimed to evaluate the efficacy and safety of ketamine in treating SUD.

METHODS: Multiple databases were systematically searched forrandomized controlled trials (RCTs) on ketamine for SUD treatment. The primary outcome was abstinence rates. Adverse events and dropout rates were also assessed to evaluate safety and acceptability. A random-effects model was used to conduct the meta-analysis.

RESULTS: Fifteen RCTs with 798 participants were included; seven RCTs contributed abstinence data to the quantitative synthesis. Ketamine was associated with significantly improved abstinence at <1 month [odds ratio(OR) = 3.27, 95% CI: 1.55-6.92, I = 0%, < 0.01], but not at 1-6 months (OR = 1.74, 95% CI: 0.91-3.30, I = 0%, = 0.09). No significant difference in dropout rates was observed between the ketamine and control groups (OR = 0.74, 95% CI: 0.46-1.21, I = 0%, = 0.23). No significant between group difference was identified in adverse events, although the available evidence was limited and insufficient to establish safety conclusively.

DISCUSSION: Current evidence suggests a short-term efficacy signal for ketamine in SUD, but the evidence remains limited and insufficient to establish its efficacy and safety conclusively.