Summary: Combining low-dose ketamine with structured psychological therapy extended abstinence and reduced heavy drinking in people with severe alcohol use disorder, according to a new clinical trial.
Source: University of Exeter
People with severe alcohol use disorder remained abstinent for significantly longer when treated with controlled low doses of ketamine together with psychological therapy, a phase II clinical trial reports.
The Ketamine for Reduction of Alcohol Relapse (KARE) trial was led by the University of Exeter and funded by the Medical Research Council. It is the first randomized, double-blind phase II study to compare ketamine with placebo and to evaluate ketamine both with and without a relapse-prevention psychological intervention in people with severe alcohol problems.
Ninety-six participants who were abstinent at the start of the trial were randomly assigned to one of four groups: ketamine plus relapse-prevention therapy, ketamine plus alcohol education (therapy control), saline plus relapse-prevention therapy, or saline plus alcohol education. Treatments consisted of three weekly intravenous infusions (ketamine 0.8 mg/kg over 40 minutes or saline) alongside the assigned psychosocial intervention. Primary outcomes were percentage of days abstinent and confirmed alcohol relapse at six months.
The study found that the combination of ketamine and psychological therapy produced the strongest effect. Participants receiving ketamine with therapy remained completely abstinent for an average of 162 out of 180 days (87 percent) during the six-month follow-up—a significantly higher rate than observed in the other groups. Those in this group were more than 2.5 times as likely to be completely abstinent at the end of follow-up compared with participants receiving placebo.
Across the trial, participants who received ketamine also showed reductions in depressive symptoms at three months and improvements in liver function compared with placebo, regardless of whether they received therapy. The authors note some evidence that ketamine plus therapy may also reduce any drinking over six months, though those results were more mixed.
Before entering the study, participants reported heavy daily drinking, averaging the equivalent of about 50 pints of strong beer per week (approximately 125 UK alcohol units). Over the six months of follow-up, participants given ketamine plus therapy drank above recommended guidelines on just five days in total on average. The authors highlight that this degree of reduction in alcohol consumption substantially lowers alcohol-related mortality risk in this group.
Lead author Professor Celia Morgan of the University of Exeter commented: “Alcoholism can destroy lives, and we urgently need new ways to help people cut down. We found that controlled, low doses of ketamine combined with psychological therapy can help people stay off alcohol for longer than placebo. This is extremely encouraging, as we normally see three out of every four people returning to heavy drinking within six months of quitting alcohol, so this result represents a great improvement.”
Professor Morgan emphasized safety considerations: “Previously, there were concerns about using ketamine in people with alcohol use disorder because of potential liver problems, but this study showed ketamine was safe and well tolerated in a clinical setting. In fact, liver function improved in the ketamine group, likely because participants drank much less alcohol.” She added that this phase II trial aimed primarily to assess safety and feasibility and that a larger trial is needed to confirm these findings.
Professor Anne Lingford-Hughes of Imperial College London, a co-author, said: “The KARE trial is a significant step towards a new approach for treating alcohol use disorder. The trial shows that ketamine therapy, when paired with psychological support, may help reverse the harms caused by alcohol dependence.”
Qualitative research with a subset of KARE participants explored how ketamine-assisted therapy affected people’s psychological experience. Participants described a shift in perspective during ketamine infusions—an “observer state” or sense of oneness—which helped them re-evaluate their relationship with alcohol and reduced the urge to self-medicate. One participant noted that feeling less focused on daily worries made drinking feel less necessary.
Interviewees described the combination of an intense ketamine experience followed by guided therapy as particularly valuable. One person explained that the ketamine session created an opening, and the therapist then provided new ways of thinking that helped sustain long-term change.
AWAKN Life Sciences, a biotechnology company developing psychedelic-assisted therapies for addiction, has licensed the therapy from the University of Exeter to offer in clinics and partnerships. The university and AWAKN have also agreed with Devon Partnership NHS Trust to explore NHS readiness for ketamine-assisted psychotherapy. Anthony Tennyson, Chief Executive of AWAKN, said the results offer a promising new treatment option for an area that has seen little innovation for many years.
Patrick Chinnery, MRC Clinical Director, commented that while further research is required, funding for this clinical neuroscience study has helped produce early findings that could pave the way to more effective relapse-prevention treatments for alcohol use disorder.
The study was led by the University of Exeter in collaboration with Imperial College London and University College London. Researchers stress that ketamine should only be used as part of a carefully controlled clinical protocol; recreational use poses significant risks and does not replicate the therapeutic context and support used in the trial.
About this alcohol use disorder research news
Author: Press Office
Source: University of Exeter
Contact: Press Office – University of Exeter
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Original Research: Closed access. “Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder” by Celia Morgan et al., American Journal of Psychiatry
Abstract
Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder
Objective:
Early evidence suggested ketamine might help sustain abstinence from alcohol. The trial tested the safety and efficacy of ketamine versus placebo for increasing abstinent days in people with alcohol use disorder and piloted the added effect of combining ketamine with mindfulness-based relapse prevention compared with ketamine plus alcohol education.
Methods:
In a double-blind, placebo-controlled phase II trial, 96 patients with severe alcohol use disorder were randomized to one of four conditions: (1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, (2) three saline infusions plus psychological therapy, (3) three ketamine infusions plus alcohol education, or (4) three saline infusions plus alcohol education. Primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at six months.
Results:
Ninety-six participants (35 women; mean age 44.07 years) were included in the intention-to-treat analysis. The treatment was well tolerated with no serious adverse events linked to the study drug. Despite wide confidence intervals typical of a proof-of-concept study, ketamine was associated with a greater percentage of days abstinent compared with placebo at six months (mean difference = 10.1%, 95% CI = 1.1 to 19.0), with the largest improvement seen in the ketamine plus therapy group compared with saline plus education (15.9%, 95% CI = 3.8 to 28.1). There was no statistically significant difference in relapse rate between the ketamine and placebo groups.
Conclusions:
Three infusions of ketamine were well tolerated by patients with alcohol use disorder and were associated with more days of abstinence at six months. The findings suggest that adding structured psychological therapy to ketamine treatment may enhance outcomes, supporting the need for larger trials to confirm these effects.