Bold headline: Ketamine’s mind-altering experience isn’t what drives its success in treating alcohol use disorder.
The intoxicating or psychedelic effects that recreational ketamine users chase do not reliably predict the therapeutic benefits for people undergoing treatment for alcohol use disorder.
A new study from King’s College London and the University of Exeter, published in Addiction, questions the leading theory that the drug’s healing power comes from its strong psychedelic experiences. Instead, the research points to other mechanisms by which ketamine may help prevent relapse.
What the study looked at
- The investigation examined intravenous ketamine-assisted psychotherapy for individuals with moderate to severe alcohol use disorder, using data from the Ketamine for reduction of Alcoholic Relapse (KARE) trial conducted at the University of Exeter and University College London, with support from the Medical Research Council.
- Dr. Will Lawn, the study’s lead author and a Senior Lecturer at King’s Institute of Psychiatry, Psychology & Neuroscience, notes that participants did experience the anticipated subjective effects of ketamine—altered reality, bodily dissociation, and warped time perception—but these experiences did not explain the treatment’s impact on drinking behavior.
Key findings
- The central result challenges the common idea that ketamine’s clinical benefits stem from its acute psychoactive or mystical-like effects.
- Instead, improvements in abstinence may arise from other drug-related actions, such as altering neural networks linked to addiction or promoting the formation of new neural connections. The researchers emphasize that more work is needed to directly test these possibilities.
Expert perspective
- Professor Celia Morgan of the University of Exeter, who leads the KARE study, highlights the public health importance of alcohol use disorder in England, with over 85,000 people treated annually and many more in need.
- Morgan stresses that while ketamine produces profound psychedelic experiences in people with this condition, we still don’t know the clinical mechanism behind how those experiences relate to abstinence. The team plans to investigate brain connectivity and function changes and to optimize dosing for greater effectiveness.
- A larger UK trial, MORE-KARE, is currently recruiting individuals with alcohol problems and is funded by the NHS, with additional support from Solvonis Therapeutics.
Study design and scope
- This secondary analysis of the KARE trial involved 96 adults at two English clinical research facilities. It is the largest study to date to explore the psychological mechanisms of ketamine in substance use disorder treatment, employing a robust randomized, placebo-controlled design with a six-month follow-up.
- Participants received three weekly intravenous ketamine infusions, which produced pronounced psychoactive effects (altered reality, out-of-body sensations, perceptual distortions) relative to placebo. These effects were consistently strong across all dosing sessions, suggesting little to no tolerance development in the short dosing window.
Bottom line
- Even with noticeable psychedelic experiences, the study found no strong evidence that these experiences were the mediators of ketamine’s therapeutic benefit in reducing alcohol consumption over six months.
Controversial angle and invitation for discussion
- If ketamine’s relapse-prevention benefits aren’t driven by its psychedelic effects, should researchers and clinicians shift focus toward neurobiological mechanisms, brain network modulation, or dosing strategies? How might this reshape how we view psychedelic-assisted therapies for addiction?
- Do you think the emphasis on subjective experiences should be reduced in favor of exploring objective brain changes and long-term outcomes? Share your thoughts below.
