Ketamine Could Treat Alcohol Use Disorder, Study Shows

The psychedelic renaissance has ushered in new hope for the treatment of a variety of substance use disorders. A recent phase two clinical trial conducted by researchers at University of Exeter examined ketamine coupled with psychotherapy as a treatment option for alcohol use disorder (AUD), finding further evidence to support the efficacy of psychedelics for treating substance abuse. 

Ketamine has several possible mechanisms of action that may work well within the context of substance use treatments, including the enhancement of neurogenesis and synaptogenesis, the disruption of functional neural networks, blocking the reconsolidation of substance-related memories, and provoking mystical experiences.

Dr. Lawn and researchers at University of Exeter set out to further investigate the use of ketamine plus psychotherapy as a relapse prevention treatment for alcohol use disorder. Dubbed the “K.A.R.E. trial” (ketamine for reduction of alcoholic relapse), the team carried out a double-blind placebo controlled phase two clinical trial across two locations in Exeter and London. 

According to Dr. Lawn, the significant burden of disease both in the U.K. and globally was a driving rationale for the trial. Globally, the World Health Organization (WHO) estimates that AUD impacts 8.6% of men and 1.7% of women, accounting for about 5% of the burden of disease and injury worldwide.

Alcohol use disorder impacted 14.5 million people in the United States in 2019 and, according to epidemiological surveys, as many as 30% of Americans will qualify for the general DSM-5 definition of AUD at some point in their lives. In the United Kingdom, there were 8,974 deaths related to alcohol-specific causes in 2020, more alcohol-related deaths than in any of the previous 20 years. 

The first weeks following detoxification are particularly high-risk for relapse, and so another rationale for the trial was to investigate the effectiveness of psychotherapy in conjunction with ketamine—an area with relatively little empirical data as yet.

“If you’re dependent on a substance and you’re stuck in a rut, then having the flexibility to move yourself out of that rut may well be a helpful effect of ketamine,” Lawn told Lucid News. 

The trial, which was funded by the Medical Research Council, included 96 participants (61 men and 35 women), all of whom had achieved abstinence before the trial began. Its design, which utilized input from Dr. Krupitsky, included four arms: ketamine infusions plus psychotherapy, ketamine infusions plus alcohol education (as placebo for the psychotherapy), saline infusions (as placebo for ketamine) plus psychotherapy, and saline infusions plus alcohol education.

Participants were invited to attend 10 study visits, including three intravenous ketamine infusion sessions administered one to three weeks apart. Each ketamine session was immediately preceded by one and a half hours of therapy or education, and followed by another session 24 hours later. The therapy included a combination of modalities, including cognitive behavioral therapy (CBT) approaches coupled with mindfulness-based relapse prevention (MBRP).

Published online in the American Journal of Psychiatry in January 2022, results from the study were in line with what the team hypothesized. There was a significantly greater percentage of days abstinent at the 6-month follow up in the ketamine groups as compared with the saline placebo groups. 

The group who received ketamine plus psychotherapy had an average of 86% days abstinent at the six month follow-up, while the ketamine plus education group had an average of 83% days abstinent. In comparison, the saline plus therapy group had an average of 76% days abstinent while the saline plus education had an average of 69%.

While the difference between the ketamine plus therapy and placebo plus education groups was not large, according to Lawn they are “[statistically] significantly different and that, therefore, merits attention and more research. We need to unpack this further.”

Though more recent studies have shown that the active placebo midazolam does not have unintended therapeutic consequences, this study elected to use an inactive saline infusion as placebo and recognizes it as a limitation of the trial. Blinding psychedelics in clinical trials is an ongoing challenge.

Psychedelic medicines offer novel and paradigm shifting treatment options in AUD and across many other conditions, but a lot of the heavy lifting is left to the individual’s personal work. This is where integration and supportive care comes into the picture, suggested Lawn. “Ketamine is not a silver bullet and it never will be. I would like to see a study powered to really detect the interaction between ketamine and therapy.”

According to Lawn, Dr. Celia Morgan, who heads up the K.A.R.E. center at Exeter and was not available for comment, is already planning for an expanded phase three trial to replicate these findings. 

After the phase two K.A.R.E. trial was completed, Dr. Morgan and the University of Exeter agreed to license the trial’s treatment model to Awakn Life Sciences, Inc., a private clinical-biotech company. Awakn opened the U.K.’s first ketamine-assisted clinic in Bristol last year, where it charges £6,000 for a course of treatment. Awakn will also, pending regulatory approval, help fund the phase three K.A.R.E. trial. 

And while ketamine therapy is only available privately at present, Dr. Morgan and her team are working with the National Health Service in an attempt to make it more available through public health services.

“What’s really exciting about ketamine, and obviously you’re seeing this in the United States, is that it’s already a legal medicine that is commonly used in human anesthetics,” said Lawn. “Anesthesiologists are very comfortable administering it.”

This means, especially when compared to emerging psychedelic therapies like MDMA and psilocybin, that ketamine is already feasible and scalable. “It is deliverable, feasible and scalable—and that’s exciting.”