Should we use this controlled drug to treat addictions?
STUDY: Hakami AY, Frontiers in Psychiatry 2026
STUDY TYPE: Narrative review
FUNDING: Independent
Background
Alcohol and cocaine use disorders have few pharmacologic options. Ketamine and esketamine have moved into addiction trials because they trigger rapid synaptic rewiring that may loosen the grip of drug-related cue memories.
The Study
This review pulls together small, randomized trials, laboratory studies, and mechanistic work on ketamine across alcohol, cocaine, and opioid use disorders, plus its safety and abuse-liability data.
Summary
Alcohol use disorder: a single ketamine infusion with motivational therapy increased daily abstinence and delayed relapse compared to an active control (midazolam). A larger trial pairing ketamine with mindfulness-based relapse prevention showed mixed results, with a positive trend in days abstinent, but non-significant difference on the co-primary outcome of relapse (it also failed on the blind with 95% of patients on ketamine correctly guessing their assignment).
Cocaine use disorder: one trial found 48% end-of-study abstinence with ketamine versus 11% with midazolam, and craving scores ran 58% lower.
Opioid data are fewer and older, largely from withdrawal protocols using anesthesia induction that’s no longer standard practice.
Across trials, no cases of diversion or new ketamine use disorder turned up, but this has been a problem in the less controlled real-world settings. Cumulative dosing in these protocols ran roughly 90 to 200-fold below what heavy recreational users take, which likely explains why the bladder and liver toxicity seen with recreational use hasn’t shown up in supervised programs.
Practice Implications
- Treating an addiction with an addictive medicine is controversial, and needs better research than what we have here.
- Fun fact: The first psychiatric use of ketamine was to treat alcohol use disorder in the former Soviet Union. More on that history in our Carlat Podcast.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
