Dakwar · The American journal of psychiatry 2019 · randomized controlled trial · n=55

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.

Cited 183 times in the scientific literature.

Level 2 - randomized trial

Randomized controlled trial

PubMed 31230464 · doi:10.1176/appi.ajp.2019.18101123 · record verified 2026-08-31

What was done

Fifty-five cocaine-dependent adults were randomized during a 5-day inpatient stay to receive a single 40-minute intravenous infusion of either ketamine (0.5 mg/kg) or an active control (midazolam). Concurrently, participants began a 5-week course of mindfulness-based relapse prevention. Cocaine use was evaluated via self-report and urine toxicology. The primary outcomes were end-of-study abstinence (over the final 2 weeks) and time to relapse (defined as first use or dropout).

What was found

In an intent-to-treat analysis, 48.2% of participants in the ketamine group maintained abstinence over the last 2 weeks compared with 10.7% in the midazolam group. The ketamine group had a 53% lower risk of relapse (hazard ratio = 0.47, 95% CI = 0.24, 0.92) and 58.1% lower craving scores throughout the trial (95% CI = 18.6, 78.6) compared to the midazolam group. Both infusions were well tolerated with no dropouts due to adverse events.

Why it matters

This trial provides randomized evidence that a single subanesthetic ketamine infusion can significantly enhance the efficacy of behavioral therapy for cocaine dependence, a disorder with limited pharmacotherapeutic options.

Limits

The sample size was small (N = 55), the total follow-up duration was short (5 weeks), and long-term durability of abstinence beyond the trial period was not evaluated.

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