Ketamine-assisted therapy could help heavy drinkers stay sober longer — study

Alex, a 42-year-old father of two living in South London, took every opportunity to go out for a drink. His career as a freelance sports photographer facilitated the outings, which always ended with more drinking once he got home.

“I’d say I was on the moderate end of having a drinking problem, which I suspect is quite relatable to a lot of people. I wasn’t missing any work deadlines and I was coping in my everyday life, but I wanted to stop drinking every day and I just couldn’t do it,” he says in a statement.

Alex was one of 100 people who joined an ongoing clinical trial to investigate whether low-dose ketamine paired with psychotherapy could help alcoholics in remission stay sober. The phase II results of the trial, dubbed Ketamine for reduction of Alcohol Relapse (KARE), suggest that combined therapy may be more effective than existing addiction treatments. The researchers plan to test it further in a phase III trial, which would include far more people — if it succeeds, it could become the first new treatment for alcoholism in decades.

WHAT’S NEW — This phase II clinical trial is the first of its kind to test whether a low dose of ketamine, combined with one-on-one therapy sessions, can prevent people from returning to heavy drinking immediately after quitting. Compared to a control group who did not receive ketamine, participants were 2.5 times more likely to abstain from drinking through the end of the trial.

According to Celia Morgan, a professor of psychopharmacology at the University of Exeter in the United Kingdom and the study’s lead author, ketamine shifts people’s mindsets, allowing them to see old problems in new ways.

“It makes the brain more receptive to new learning by stimulating a process called synaptic plasticity where the brain is more able to make new connections,” Morgan tells Inverse.

Ketamine acts on the brain by essentially blocking a receptor that helps neurons deliver messages to other neurons effectively. Previous research shows this particular receptor plays a key role in learning and memory, and that changes to the receptor may influence behaviors related to addiction — including future behavioral patterns.

The results were published Tuesday in the American Journal of Psychiatry.

“Our interviews with patients suggested that feeling detached from themselves made them feel more connected with the world around them.”

WHY IT MATTERS — Ketamine is the only psychedelic approved by the U.S. Food and Drug Administration — specifically, the agency approved ketamine nasal spray for treatment-resistant depression in 2019. But a growing body of research suggests ketamine can help treat other mental health conditions, including addiction, PTSD, and suicidality, when existing treatment options have failed.

Ketamine “is a dissociative anesthetic,” Morgan says, “so we tend to see it as detaching people. But our interviews with patients suggested that feeling detached from themselves made them feel more connected with the world around them and this helped with recovery from alcohol.” To understand the implications, consider that the people in the ketamine plus therapy group only drank heavily on five days during six months. By cutting their alcohol consumption dramatically, ketamine-assisted therapy also cut their risk of death from alcohol-related problems during that time from one in eight to one in 80.

“We haven’t had new treatments for alcoholism in around 50 years,” Morgan says. “We’re certainly not advocating taking ketamine outside of a clinical context. Street drugs come with obvious risks, and it’s the combination of a low dose of ketamine and the right psychological therapy that is key, as is the expertise and support of clinical staff. This combination showed benefits still seen six months later in a group of people for whom many existing treatments just don’t work.”

HOW THEY DID IT — The study includes 96 people with moderate to severe alcohol use disorder who did not drink during the trial. In fact, to be included in the study, participants had to abstain from drinking completely for at least 24 hours before being screened for the trial. Alex went cold turkey for 14 days before starting the study, the longest he had been without a drink in two decades. On average, participants consumed 125 units of alcohol per week — the equivalent of about 63 beers. (One unit is the amount of alcohol the average person can metabolize in an hour.) Forty-five percent of participants also had anxiety disorder and 40 percent had depression.

Participants in the trial were divided into four separate groups. Some of the participants received seven sessions of therapy or alcohol education and no ketamine, while others had up to three infusions of ketamine paired with either therapy or alcohol education.

People who received ketamine combined with therapy stayed completely sober for 162 of the 180 day follow-up period, or 87 percent of the days. This was significantly higher than any of the other groups. Those in either of the ketamine groups also reported lower depression after three months and better liver function than those on placebo.

Taken together, the results suggest ketamine infusions, combined with more traditional therapy, could help prevent relapse after people quit drinking.

WHAT’S NEXT — This clinical trial set out to test whether or not ketamine-assisted therapy for alcohol use disorder is both feasible and safe — and it did it. Given the trial’s success, Morgan’s team is now ready to move on to a phase III clinical trial, in which they’ll repeat the study on a larger scale — with more people — to validate the results.

“We now have an early signal that this treatment is effective. It shows ketamine works better when given with therapy than without and that it can have long-lasting effects still seen at six months after a relatively short treatment. Now we need a bigger trial to see if we can confirm these effects,” Morgan says.

This study is geared to the UK — there, health regulators will need to review the data before any next moves are confirmed. If the results do show ketamine-assisted therapy to be an effective treatment for alcoholism, then it is likely there will be more trials and more research needed before it becomes an available option in the clinic.

But in places like the U.S., where ketamine is already an approved treatment for another condition, the trial could help make the argument for an expanded approval for alcohol addiction treatment sooner.

Abstract:

Objective:

Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control.

Methods:

In a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned 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. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up.

Results:

Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups.

Conclusions:

This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.