Can A Single Dose of Ketamine Improve Cocaine Use Disorder Treatment Outcomes?

Currently, there are no FDA-approved medications for the treatment of cocaine use disorder. Ketamine has demonstrated antidepressant effects in randomized clinical trials and decreased cocaine craving and use in laboratory settings at sub-anesthetic doses. Investigators randomized 55 participants with DSM-IV cocaine dependence, past 30-day cocaine use, and no psychiatric co-morbidity to a 40-minute intravenous infusion of either ketamine or midazolam. Both groups received mindfulness-based relapse prevention (MBRP) psychotherapy. In this 5-week study, participants were hospitalized for 5 days, received the infusion on day 2, and received MRBP during the hospital stay and for 4 weeks afterwards.

• Over the last 2 weeks of the trial, 48% of participants in the ketamine group were abstinent from cocaine use, compared with 11% in the midazolam group.
• Craving scores were 58% lower in the ketamine group than the midazolam group, controlling for route of use.
• The only reported adverse effect was mild sedation lasting less 12 hours. There were no persistent psychiatric disturbances or incidences of new unhealthy substance use.

Comments: In this randomized trial, a single infusion of ketamine significantly reduced cocaine use and craving compared with midazolam. Since both groups received MBRP, it is unclear whether MBRP is necessary for ketamine to be effective. Limitations include the study’s small size and exclusion of people with psychiatric co-morbidity. Furthermore, participants were hospitalized for 5 days, which may be difficult to implement in other settings.

Tae Woo (Ted) Park, MD

Reference: Dakwar E, Nunes EV, Hart CL, et al. A single ketamine infusion combined with mindfulness-based behavioral modification to treat cocaine dependence: a randomized clinical trial. Am J Psychiatry. 2019;176(11):923–930.