Ketamine's Therapeutic Role in Substance Use Disorders: A Narrative Review.
Alexander Thomas, R Andrew Chambers
NeuroSci August 27, 2025 DOI: 10.3390/neurosci6030083 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Randomized Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine Addiction Esketamine |
| Keywords | Nmda n-methyl-d-aspartate Case reports Cohort studies Controlled trial Retrospective studies Treatment |
| Citations | 4 |
| Key findings | Ketamine, tested in nine randomized blinded controlled trials targeting cocaine, alcohol, opioid use disorder, and nicotine, suggests efficacy for addiction when combined with psychotherapies, particularly at doses producing mystical or psychedelic experiences. |
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.