Trial of Ketamine Therapy for Alcohol Use Disorder Reports Positive Findings

A clinical trial exploring the use of ketamine-assisted psychotherapy to treat alcohol use disorder (AUD) has reported positive results.

Improved abstinence

The study findings, published in the American Journal of Psychiatry, show that ketamine-assisted therapy led to a 90% abstinence rate for AUD patients in the following six months. The risk of death for participants in the study, who regularly consumed up to 128 units of alcohol per week prior to the intervention, was reduced 10-fold after the ketamine therapy, which also utilized an AUD-specific form of mindfulness work. The participants were on average, in their mid-forties and 61 of 96 were male.

Celia Morgan, a professor of psychopharmacology at the University of Exeter and senior author on the trial paper, told Technology Networks that the study’s key finding was that a “quite short-lasting course of ketamine-assisted psychotherapy produced a really long-lasting effect on alcohol use”.

The study examined volunteers over a six-month period, during which their alcohol intake was monitored through an anklet wearable. Most other approved interventions for AUD, such as the opioid receptor blocker naltrexone, must be taken daily for several months, whereas the volunteers in Morgan’s trial required much shorter pharmacological interventions – three 40-minute visits to a ketamine clinic in the first two months of the trial, where they were administered with a 0.8 mg/kg dose of the drug intravenously.

The volunteers were split into four groups:

• A group that received ketamine doses plus therapy sessions on alternate weeks
• A group that received ketamine doses plus alcohol education sessions on alternate weeks
• A group that received saline placebo doses plus therapy sessions on alternate weeks
• A group that received saline placebo doses plus alcohol education sessions on alternate weeks

As Morgan expected, the percentage of days abstinent in the six months after randomization was highest for the ketamine plus therapy group, where, on average, users refrained from drinking on 162 of 180 days. This was followed by the ketamine plus alcohol education group, with the two placebo groups having the lowest number of abstinent days.

Preventing relapse

Three-quarters of newly sober people with AUD will be back drinking at toxic levels within a year, Morgan said. So, while the performance of the ketamine group is impressive, that the saline plus alcohol education control groups achieved abstinence on 70% of days in the subsequent period may be surprising. Morgan said that the difference between the two doesn’t sound huge but could have a significant clinical benefit for patients: “It has quite dramatic impacts on things like mortality. We know alcohol is one of the leading causes of preventable death in people under 50. The patients in our study would have had a one in eight chance of dying prematurely and thatwas reduced to one in eighty as a result of the treatment. That’s one of the most important findings – that this treatment can actually save lives.”

That the placebo group performed so highly is both a problem shared by all clinical trials, and an issue that Morgan suggested could be minimized in future trial phases by tweaks to the current protocol. The monitoring anklet used, which detects alcohol levels through sweat, vibrates every 30 minutes, Morgan pointed out. This may have inadvertently served as an additional intervention and encouragement to stay sober even for placebo patients.

Next steps

Morgan is cautious about the results, pointing out that definitive conclusions about the effectiveness of the intervention will need to wait until the trial’s next step, a larger Phase III study. While the highest relapse rates after six months – defined as one or more days of heavy drinking – were not significantly different between trial conditions, the lowest relapse rates were seen in the ketamine and psychotherapy group, suggesting a more highly powered study could unearth significant data. “It's important to note as well, that the reductions we’ve seen in drinking behavior from harmful, very high risk to low risk, are really important for people's physical and mental health, as well as reducing their risk of dying. These are important changes, and we kind of fixate a bit, I think, on total abstinence,” said Morgan.

Morgan points out that many alcoholics don’t want to stop drinking altogether, which can discourage them from seeking treatments that they perceive to require rigid, permanent sobriety. “Is there a way,” asked Morgan, “that psychedelic drugs, like ketamine, might be able to change your relationship with alcohol such that you might be able to reduce your drinking down to very low-risk drinking, a more controlled drinking pattern? That might engage more people in treatment.”

Morgan’s study highlights the immense challenges of treating AUD and the wide spectrum of people affected by it, but also provides what she hopes is a hopeful future for psychedelics in the area. Her intervention is currently licensed by psychedelics clinic company Awakn Life Sciences, but the team, have partnered with a local NHS trust to explore their readiness for administering ketamine-assisted therapy, Morgan said. “It's really exciting to see these findings,” she concluded, “and to find a positive effect that we can take forward.”

Reference: Grabski, M., McAndrew, A., Lawn, W., et al. Adjunctive Ketamine With Relapse Prevention–Based Psychological Therapy in the Treatment of Alcohol Use Disorder. Am J Psychiatry. 2021.