Background: Conventional psychological and pharmacological substance abuse treatments are limited to moderate effect sizes and fail to magnify outcomes when combined. Analog psychedelic agents N, N-dimethyltryptamine (DMT) and 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) show therapeutic potential for treatment-resistant psychiatric disorders including substance addictions. Methods: This systematic review and meta-analysis synthesized DMT intervention studies (1960–2024) across PubMed, PsycINFO, Web of Science, and EBSCO databases, calculating pooled effects for substance use reduction. Subgroup sensitivity analyses examined the impacts of psychotherapy, population type, and treatment design on outcomes. Results: DMT yielded a large overall effect size for substance abuse reduction ( g = 0.94, 95% CI: 0.56–1.31, p < 0.0001), with superior efficacy for drug use ( g = 1.35, 95% CI: 0.63–2.07, p < 0.0001) compared to alcohol use ( g = 0.65, 95% CI: 0.31–0.99, p < 0.0001). Studies incorporating psychotherapy showed significantly greater effects ( g = 1.38, 95% CI: 1.06–1.71, p < 0.0001) than those without ( g = 0.60, 95% CI: 0.09–1.12, p < 0.0001), with significant subgroup difference ( p = 0.0121). High risk of bias and high heterogeneity were observed ( I 2 = 96.9%), with effects varying by substance type and treatment context. No publication bias was detected. Conclusion: When combined, available studies demonstrate DMT’s potentially substantial post-treatment efficacy for substance misuse, particularly with psychotherapy. Effect magnitudes vary by abused substances. Included studies had substantial methodological limitations and high risk of bias. Reported effects should therefore be interpreted as preliminary rather than indicative of established efficacy. Furthermore, the use of exploratory subgroup analyses in this review can only conclude that DMT efficacy for treating alcohol and substance abuse disorders is highly heterogeneous, depending on study and treatment design. If sustained positive results are clearly demonstrated in future research, it might position DMT-assisted psychotherapy as an effective, economical alternative to conventional treatments.
Wallace et al. (Sun,) studied this question.