The psychedelic effects recreational users often seek from taking ketamine do not predict the therapeutic benefits for people being treated for alcohol use disorder, according to new research from King's College London and University of Exeter.
The popular theory, which says that ketamine may have its therapeutic benefits because it produces strong psychedelic effects, has been called into question by the new study, published in Addiction. The findings suggest the treatment response may be down to other effects of the drug.
The research, led by the Institute of Psychiatry, Psychology & Neuroscience at King's, is the largest randomised controlled trial to date examining the use of intravenous ketamine-assisted psychotherapy for individuals with moderate to severe alcohol use disorder. It uses data from the Ketamine for reduction of Alcoholic Relapse (KARE) clinical trial at the University of Exeter and University College London.
For the first time, we thoroughly investigated the acute psychoactive effects of repeated ketamine infusions in people with alcohol use disorder. The effects didn't predict ketamine's therapeutic benefit, which leaves open other psychological or neural mechanisms that need to be investigated.
Dr Will Lawn, Senior Lecturer at King's College London and study lead
Researchers carried out a secondary analysis of the KARE clinical trial which was conducted at two clinical research facilities in England involving 96 adult participants and sought to clarify the role of ketamine's psychoactive effects in supporting abstinence from alcohol.
Participants receiving three weekly infusions of intravenous ketamine reported marked psychoactive experiences, including altered reality, out-of-body sensations, and perceptual distortions, compared to those receiving placebo. These effects were consistently strong across all three dosing sessions. This suggests little to no development of tolerance to ketamine's subjective effects over the short dosing schedule.
But despite the pronounced psychoactive effects, the study found no significant evidence that these experiences mediated ketamine's therapeutic benefit in reducing alcohol consumption. The percentage of days abstinent from alcohol over six months was not predicted by the intensity of subjective drug effects.
Professor Celia Morgan from the University of Exeter and KARE trial lead said: "Alcohol use disorder remains a significant public health concern, with over 85,000 people in England receiving treatment annually - but many more still requiring treatment. While several effective treatments exist, there is a pressing need to diversify options and improve long-term outcomes.
"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. Now 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."
It was a privilege to analyse the KARE dataset for my final year research project, and then take it all the way through to publication 18 months later. With close supervision from Dr Will Lawn, we carefully investigated what predicts treatment success in patients with alcohol use disorder being treated with ketamine. Against our hypotheses, we did not find that ketamine's well-known profound psychoactive effects predicted abstinence from alcohol.
Cassie Bloy, BSc Psychology Graduate at King's College London and first author of the study
Cassie Bloy conducted the research as part of her final year dissertation on the Psychology BSc programme
