Many researchers have assumed ketamine’s psychedelic effects are central to its therapeutic value.
However, a new analysis from King’s College London and the University of Exeter found no link between these experiences and improved alcohol abstinence. The results suggest that ketamine’s benefits in alcohol use disorder (AUD) may come from biological effects in the brain instead.
Ketamine and alcohol use disorder treatment
AUD can be difficult to treat. In England alone, more than 85,000 people receive treatment each year; however, many relapse even after therapy or medication.
“Alcohol use disorder remains a significant public health concern. While several effective treatments exist, there is a pressing need to diversify options and improve long-term outcomes,” said co-senior author Dr. Celia Morgan, a senior lecturer from the University of Exeter.
Ketamine, originally developed as an anesthetic, is now used in some countries for depression. Its success has led researchers to start testing it for addiction. In the earlier Ketamine for Reduction of Alcoholic Relapse (KARE) trial, people who received ketamine alongside therapy stayed sober for a greater percentage of days compared to those given a placebo.
“We previously showed that ketamine has promise for helping people with alcohol use disorder remain sober,” said co-author of both studies, Dr. Will Lawn, a senior lecturer from King’s College London.
Many scientists believe ketamine works because of the unusual experiences it produces, such as feeling detached from the body or perceiving time differently. Similar effects seen with drugs like psilocybin have been linked to improvements in depression and addiction.
However, whether these subjective experiences are responsible for recovery or whether ketamine works through other effects in the brain remains unknown.
The team carried out a secondary analysis of the KARE trial to test directly if ketamine’s psychoactive effects explain its clinical benefit in AUD.
Ketamine’s psychoactive effects do not predict recovery
The researchers analyzed data from 96 adults with moderate-to-severe AUD who had taken part in the original KARE trial. Participants received three intravenous infusions of ketamine at a dose of 0.8 mg per kilogram of body weight, given once a week, or a saline placebo. All participants also received psychological therapy aimed at preventing relapse.
During each infusion, researchers measured the drug’s subjective effects, and participants rated experiences such as altered reality, visual distortions, and out-of-body sensations on numerical scales at multiple time points.
Ketamine caused strong psychoactive effects, and participants reported clear changes in perception and awareness compared to the placebo. These effects appeared during each infusion and remained similar across sessions, showing little sign of tolerance.
However, the intensity of these subjective effects did not predict who stayed sober.
Statistical tests showed no meaningful relationship between how strongly someone experienced ketamine’s psychoactive effects and their abstinence outcomes, separating the experience of the drug from its therapeutic impact. Ketamine helped reduce alcohol use, but the altered state itself did not explain why.
Ketamine’s therapeutic effects may work through brain changes
The findings challenge a widely held assumption in psychedelic therapy, suggesting ketamine may work through mechanisms other than the subjective experience it produces.
“Our results challenge the popular theory that the therapeutic benefits of ketamine are driven by its acute psychoactive or mystical-like effects. Instead, our findings suggest other possible reasons why ketamine prevents relapse, such as its ability to alter networks in the brain related to addiction or stimulate new neural connections to form,” said Lawn.
Studies in depression suggest that ketamine can promote synaptic plasticity and reorganize brain circuits involved in mood and reward; these similar processes may help people with addiction.
If ketamine’s therapeutic effect does not depend on the psychedelic experience, future treatments might also aim to keep the benefit while reducing unwanted psychological effects, potentially making treatment easier to deliver and safer for some patients.
“Our research underscores that ketamine induces profound psychedelic effects in people with alcohol use disorder, but we still don’t know the clinical reason why these experiences promote abstinence,” said Morgan.
“More research is needed to directly test these hypotheses,” said Lawn.
“We need to explore the roles of brain connection and function changes in ketamine’s therapeutic action, as well as refining dosing to make it as effective as possible. We are now running a larger version of this study across the UK, currently recruiting people with alcohol problems, to try and provide those answers,” Morgan added.
Reference: Bloy C, Sarma A, Marsh B, et al. The psychoactive effects of repeated ketamine infusions and their mechanistic role in the treatment of alcohol use disorder: Secondary analysis of a randomised controlled trial. Addiction. 2026. doi: 10.1111/add.70320
This article is a rework of a press release issued by the University of Exeter. Material has been edited for length and content.
