Ketamine's Therapeutic Role in Substance Use Disorders: A Narrative Review.

Interest in ketamine as a treatment for substance use disorders has grown because it blocks NMDA glutamate receptors and because glutamate signaling is linked to depression and addiction. This narrative review covers clinical evidence from the 1970s to 2025, focusing on randomized blinded controlled trials. Nine such trials have tested ketamine for cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study). The evidence suggests ketamine is effective for addiction when combined with psychotherapies, especially at doses that produce mystical or psychedelic experiences. The review calls for more rigorous studies to determine which addictions ketamine may treat, optimal dosing, the role of concurrent psychotherapies, safety monitoring, and contraindications.

Study at a glance

Abstract

Interest in ketamine as a novel treatment for substance use disorders (SUDs) has been increasing due to its N-methyl-D-aspartate (NMDA) glutamate receptor antagonism and mounting evidence that glutamate neurotransmission is involved in the pathogenesis of both depression and addictions. This narrative review provides an outline of clinical evidence reported in the literature from the 1970s to 2025 that examines the efficacy of ketamine for the treatment of SUDs, focusing primarily on randomized blinded controlled trials (RBCTs). Key cohort studies, retrospective studies, secondary analyses, case reports, and relevant basic neuroscience studies are reviewed to complement the more rigorous human controlled trial data. Thus far, ketamine has been tested in nine RBCTs targeting cocaine (three studies), alcohol (three studies), opioid use disorder (two studies), and nicotine (one study), suggesting efficacy for addiction in combination with psychotherapies, and often when doses produce subjectively reported mystical or psychedelic experiences. This review highlights promising preliminary evidence, and the need for more rigorous studies to elucidate the scope of drug addictions ketamine may target, its optimal dosing or route of administration, the importance of concurrent psychotherapies, professional supervision and safety monitoring, and which psychiatric comorbidities or contexts may contraindicate its use for SUDs.