A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial

This randomized, double-blind, active placebo-controlled pilot study (n=40) examined the effects of ketamine (49.7mg/70kg, n=17) or the active control midazolam (1.75mg/70kg, n=23) combined with motivational enhancement therapy to treat patients with alcohol use disorder. The preliminary data showed that a single ketamine infusion in combination with motivational enhancement therapy improves measures of drinking in patients with alcohol use disorder.


Objective: Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes.

Methods: Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion.

Results: Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events.

Conclusions: A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.”

Authors: Elias Dakwar, Frances Levin, Carl L. Hart, Cale Basaraba, Jean Choi, Martina Pavlicova & Edward V. Nunes

Study details

Compounds studied

Topics studied
Addiction Alcohol Use Disorder

Study characteristics
Placebo-Controlled Active Placebo Double-Blind Randomized



Authors associated with this publication with profiles on Blossom

Elias Dakwar
Elias Dakwar, MD researches novel treatments for addictions with the support of several grants from NIDA and NIAAA. A special focus of his research has been evaluating sub-anesthetic ketamine infusions for cocaine use disorders in both laboratory and clinical settings, as well as investigating ketamine infusions as an adjunct to mindfulness-based treatment, motivational interviewing, and other behavioral frameworks for alcohol, cannabis, and opioid use disorders. He has a more general interest in the impact of non-ordinary experiences, and of the interventions that might occasion them, in psychiatric treatment.

Carl Hart
Dr. Carl L. Hart is the Ziff Professor of Psychology in the Departments of Psychology and Psychiatry at Columbia University.


Institutes associated with this publication

Columbia University
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Compound Details

The psychedelics given at which dose and how many times

Ketamine 1.75 - 49.7

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