A first-of-its-kind clinical trial at the University of Exeter has looked at the potential of ketamine-assisted therapy to reduce alcohol relapse – and it’s promising.
The phase 2 study, called Ketamine for Reduction of Alcohol Relapse (KARE), determined that small doses of ketamine, combined with therapy, helped former drinkers avoid alcohol for more days over a period of six months compared to the placebo group.
They were also 2.5 times more likely to stay completely abstinent for the six months.
“It’s hugely encouraging because we normally see three out of four people return to heavy drinking within six months of quitting alcohol, so this result represents a big improvement,” said Celia Morgan of Exeter, lead author of the study, in a statement. .
A special K: Ketamine is more than a club drug or a vet’s friend – it’s actually an extremely useful and relatively safe anesthetic, considered essential by the World Health Organization.
It is also, at low doses, a psychedelic and powerful antidepressant.
The drug’s antidepressant effects are dramatic and have recently become commonplace, with the FDA approving a ketamine-derived nasal spray for severe depression, ketamine infusion clinics opening up across the country, and researchers looking into its structure. chemical in search of new antidepressants.
And although the Exeter study is the first clinical trial of using ketamine to help prevent relapse, the idea of using the anesthetic to help treat alcohol dependence is actually decades old.
“There were some early studies in the 1980s in St. Petersburg, Russia, by a psychologist named Evgeny Krupitsky,” Morgan tells me. Krupitsky gave ketamine to alcohol addicts in an inpatient unit and, combined with therapy, had “truly amazing results.”
This research, combined with Morgan’s 20 years of study of the drug and its emergence in the psychedelic research renaissance, helped inspire the work of the Exeter team.
Help people stay dry: For their new study, published in The American Journal of Psychiatry, the researchers recruited 96 subjects who suffered from severe alcohol use disorders, were currently abstinent and were not taking antidepressants.
The volunteers were randomly placed into four groups, to measure both the impact of ketamine and the therapy they received. Half of the volunteers received three infusions of ketamine or a placebo (saline solution), and half of each group received either psychological therapy or alcohol education. “It was quite a complex study to conduct,” says Morgan.
At low doses, ketamine is a promising psychedelic and antidepressant.
The study’s primary outcomes were self-reported number of days abstinence and relapse avoidance, which they defined as one or more heavy drinking days over six months.
The ketamine groups were given the drug at a slightly higher dose than that used for depression because people with alcohol dependence have been shown to have a tolerance to the drug, Morgan says.
A good trip: The dose, however, was low enough to induce a psychedelic experience, and research indicates that a trip is a key part of the therapeutic potential of psychedelics.
“People were like meeting from the future or stepping into Alice in Wonderland,” Morgan says. One patient even met God, who offered him two wishes, one of which was to regrow his hair.
But these experiences can be transformative for patients.
“The sense of oneness I felt and the feeling of not focusing on worries and little things anymore is helpful in improving my relationship with alcohol,” one patient said in the Exeter statement.
“Because I think I’ve used alcohol as self-medication and as a blocking and avoidance mechanism. And I think feeling like these issues are less prevalent or at least less prominent means I feel less motivated to drink.
Patients who received ketamine had “a significantly higher number of days abstinence from alcohol,” the researchers wrote in their paper, with the group who received ketamine and psychological therapy having the greatest benefit, remaining completely sober for 162 out of 180 days, or 86% of the six-month study period.
The lowest performing group, which received a placebo and alcohol education, remained completely sober for just under 69% of the study period.
It should be noted that these results had wide confidence intervals – meaning the true magnitude of change was difficult to judge – because the study was small.
“I think this is an exciting study that highlights a potential new therapeutic action of ketamine for the treatment of drug addiction, which is somewhat paradoxical, given the significant risk of abuse associated to recreational use of ketamine,” said John Krystal of Yale, whose lab pioneered ketamine. as an antidepressant, told me by e-mail.
Because of this potential for abuse, there has been some hesitation in prescribing ketamine to people with addictive disorders, even though its antidepressant effects may be helpful in curbing these addictions.
Before it can be used in the clinic, “we will need to see this work replicated and scaled up to fully understand the clinical impact of this intervention,” says John Krystal of Yale.
From concept to clinic: Interestingly, there was no significant difference in the odds of relapse (one or more heavy drinking days) for patients on ketamine over the six months, despite the detectable increase in abstinence – a reminder that, as exciting as the results are, this is not a definitive result. The result could be a study window factor; a longer follow-up period may have yielded more pronounced differences, Morgan says by email.
Before it can be used in the clinic, “we will need to see this work replicated and scaled up to fully understand the clinical impact of this intervention,” says Krystal.
The next step for Morgan and his colleagues is to do just that. They are starting a phase 3 trial with NHS support, enrolling a larger cohort of patients – including those on antidepressants.
They hope to start the trial within the year.
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