A single dose of ketamine may be able to curb harmful drinking behavior by "rewriting drinking memories," according to a study published Tuesday in the journal Nature Communications.
The researchers say that, when coupled with an exercise involving beer that pulls memories of alcohol to the foreground, there's evidence that the drug can disrupt how the brain associates these cues -- like the smell or taste of beer -- to its perceived "reward," making relapse less likely.
"It's those kinds of associations that we're trying to break down," explained study author Ravi Das, an associate professor at University College London who specializes in psychopharmacology. "We're not talking about people's explicit recollection of the fact that they drank in the past."
Ketamine is a powerful medication used in hospitals primarily as an anesthetic, though it has also been used illegally as a club drug, often referred to as Special K. It generates an intense high and dissociative effects.
"It's an intriguing approach that builds on existing literature in a couple of areas," said Dr. Henry Kranzler, a professor of psychiatry at the University of Pennsylvania Perelman School of Medicine, who was not involved in the study.
Earlier studies have explored ketamine for alcohol, cocaine and opioid addiction -- but many had small sample sizes, limited follow-up and lack of placebo, according to experts. Das said it's also difficult to blind participants to whether they've received ketamine or a placebo because of its "strong effects."
Other research has shown the drug's potential to counter depression and suicidal ideation. In March, a close relative of ketamine -- called esketamine and sold under the name Spravato in the form of a nasal spray -- was approved by the US Food and Drug Administration for treatment-resistant depression.
The new study recruited 90 "beer-preferring" people with potentially harmful drinking patterns from internet ads and separated them into groups: those who underwent an exercise involving alcohol-related cues and received intravenous ketamine in a controlled environment; those who completed the exercise but received a placebo; and those who received ketamine alone. While the authors said participants "showed a clearly harmful and problematic pattern of drinking," they were not seeking treatment for an alcohol use disorder and had not been formally diagnosed with such.
But there was some heterogeneity between the groups. While the first group reduced their drinking to the largest degree, they also happened to drink more to begin with -- "and therefore their consumption was more likely to decline, a phenomenon known as regression to the mean," explained Matt Field, a professor of psychology at the University of Sheffield in the UK, in an emailed statement.
After the treatment, there wasn't a significant difference between the three groups in terms of how much alcohol they drank. Nine months later, average weekly consumption was roughly the same across the board. The authors say this may have been influenced by losing participants to follow-up.
Field said the findings are "promising," but the claim that the full treatment protocol "leads to 'unprecedented' long-lasting reductions in alcohol consumption are not justified on the basis of this data."
Das pointed out other layers to the data, however: Those who completed the exercise and received ketamine had less desire to drink, and they drank less frequently. In addition, there was a correlation among that group between concentrations of ketamine and its breakdown products in the blood, and the reduction in how much participants drank.
"People all vary in how quickly they metabolize" and excrete ketamine and its byproducts, Das said. "That level of individual variability with ketamine actually predicts drinking outcomes subsequently."
The group that received ketamine alone saw improvements, too, but not to the same degree as those presented with alcohol-related cues, according to the authors.
Kranzler said the study is an intriguiguing proof-of-principle that he suspects will spur subsequent studies needed to replicated these findings.
But an important question, he added, "is to what degree could combined psychosocial intervention -- cognitive behavioral intervention, for example -- synergize with or at least augment the pharmacological effect" of ketamine.
"That's the kind of treatment study that I think would make a lot of sense," he added. "So this wouldn't be used in isolation."