The belief that the psychedelic effects of ketamine contribute to its therapeutic benefits in treating alcohol use disorder is being challenged by new research from King's College London and the University of Exeter. The study, published in Addiction, suggests that other factors may explain ketamine's impact on reducing alcohol relapse.
Researchers analyzed data from the Ketamine for reduction of Alcoholic Relapse (KARE) clinical trial, a randomized, placebo-controlled study involving 96 adults with moderate to severe alcohol use disorder. The trial was conducted at two sites in England and included a six-month follow-up period.
Dr. Will Lawn, lead author and Senior Lecturer at the Institute of Psychiatry, Psychology & Neuroscience at King's College London, said: "We previously showed that ketamine has promise for helping people with alcohol use disorder remain sober and these new findings demonstrate those receiving intravenous ketamine experience the expected subjective effects from the drug, including feelings of altered reality, bodily dissociation and warped time perception.
"However, 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. More research is needed to directly test these hypotheses."
Participants who received three weekly infusions of intravenous ketamine reported significant psychoactive experiences—such as perceptual distortions and out-of-body sensations—compared with those given a placebo. These effects remained strong throughout all dosing sessions without evidence of short-term tolerance development.
Despite these pronounced subjective experiences, researchers found no significant link between the intensity of psychedelic effects and improvements in abstinence rates over six months. In other words, experiencing stronger drug-induced states did not predict greater success in remaining sober.
A larger clinical trial called MORE-KARE is now underway across the UK under Professor Morgan’s leadership. This new study aims to further investigate how ketamine might support people struggling with alcohol problems.
