Ketamine's Therapeutic Benefits Not Linked to Psychedelic Effects in Alcohol Use Disorder

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. A study from King's College London and the University of Exeter, published in Addiction, challenges the popular theory that ketamine may have its therapeutic benefits because it produces strong psychedelic effects, suggesting the treatment response may be down to other effects of the drug.

The research provides new insights into the use of intravenous ketamine-assisted psychotherapy for individuals with moderate to severe alcohol use disorder. It used data from the Ketamine for reduction of Alcoholic Relapse (KARE) clinical trial at the University of Exeter and University College London, supported by the Medical Research Council. The secondary analysis of the KARE clinical trial, conducted at two clinical research facilities in England and involving 96 adult participants, 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, suggesting little to no development of tolerance to ketamine's subjective effects over the short dosing schedule. However, 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.

The 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. 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.

Researchers are now running a larger version of this study across the UK, currently recruiting people with alcohol problems, to try and provide answers about 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. The study is the largest to date examining the psychological mechanisms of ketamine in substance use disorder treatment, with a robust randomised, placebo-controlled design and a six-month follow-up period.

Meanwhile, addiction remains a serious public health problem in the United States, with nearly 80,000 people nationwide dying of drug overdoses in 2024 alone. About 178,000 people in the United States die from excessive drinking each year. Alcohol use disorder increases the risk of unintentional injuries, car accidents, and suicide, and also contributes to cancer, heart disease, liver disease, birth defects, and developmental disabilities.

To address addiction, researchers are working to develop better treatments, including medications, behavioral therapies, and integrated health services. One effective behavioral treatment is cognitive behavioral therapy (CBT), which is designed to change the thought processes that lead to unhealthy behaviors. In the case of alcohol use disorder, it might involve identifying feelings and situations that contribute to heavy drinking and developing skills to deal with those feelings and situations.