BACKGROUND AND AIMS Substance Use Disorders (SUDs) involve diminished control, risky use, impaired social interactions, and physical dependence. Despite their global prevalence and burden, treatment options remain limited. Ketamine (KET), an NMDA receptor antagonist, may aid SUD treatment by modulating glutamatergic neurotransmission. This systematic review evaluates KET's role in SUD treatment.

METHODS This review surveyed three databases until June 2024, including 14 studies with 551 participants.

RESULTS Among the 14 studies, 6 focused on alcohol, 3 on cocaine, 4 on opioids, and 1 on cannabis. Seven studies (50 %) combined KET with psychotherapy, while seven (50 %) focused solely on KET's pharmacological effects. KET dose ranges varied from 0.11 mg/kg to 2.0 mg/kg and study primary endpoints ranged from less than a day to two years. The results of the included studies demonstrated KET's efficacy across various SUDs. In Alcohol Use Disorder (AUD), KET reduced withdrawal symptoms and benzodiazepine requirements. In Cocaine Use Disorder (CUD), KET decreased craving and increased abstinence rates. In Opioid Use Disorder (OUD), high-dose KET psychotherapy (KPT) improved abstinence and reduced craving. In Cannabis Use Disorder (CNUD), KET reduced weekly use and increased abstinence confidence.

CONCLUSIONS Conclusion: While preliminary studies suggest that KET may have short-term benefits in treating SUDs, the evidence remains limited by small sample sizes and a lack of randomized trials. Further research with larger, well-controlled studies is needed to determine optimal dosing, clarify mechanisms of action, and assess long-term efficacy and potential risks, including abuse liability, before broader clinical implementation can be recommended.