“Not Mechanized or Automatic”—Ketamine Researcher Sounds Caution Over Alcohol Study

    What really causes you to drink to excess?

    Elias Dakwar, MD says the answer is more complex than many think. Dakwar is an assistant professor of Clinical Psychiatry at Columbia University. He has conducted laboratory and clinical investigations of ketamine infusion and mindfulness training to treat cocaine use disorder.

    He wrote to Filter in relation to our recent report about a University College London study on ketamine and problematic drinking, which was published in Nature Communications on November 26. While those researchers, led by Dr. Ravi Das, summarized that ketamine treatment resulted in a decrease in problematic drinking by interrupting memory-based cognitive processes, Dakwar said there may be more factors at play.

    In the UCL study, researchers used sights, sounds and smells of beer (including actual beer) to try to cue an urge to drink for participants with harmful drinking behaviors. They followed this exercise with a ketamine infusion treatment, to test if the drug could rewrite the process of “cue-related learning.”

    “While the authors are to be commended for trying to understand the mechanism, there remain several questions,” said Dakwar. “Most importantly, it is not clear that what is going on is primarily an issue of destabilized cue associations.”

    Dakwar told Filter that his own study of cocaine-dependent participants, published in 2014, found similar results. Ketamine showed potential to affect participants’ reward-seeking behavior and improve their motivation to change problematic habits. But Dakwar noted that the participants in his study were more likely to seek temporary relief through ketamine because their cocaine use was problematic enough for abstinence in a laboratory setting to cause them strain and discomfort.

    “The larger point is that decision-making in drug users is not as mechanized or automatic as behavioral scientists suggest, with a destabilized memory alone working to disrupt the behavior,” Dakwar said. “It is a highly contextual, fluid and subjective process, with an intention to diminish inner distress often playing a major role in both motivating drug use and motivating abstinence or reduction.”

    Dakwar also pointed out an issue that other analysts have raised: The experimental group in the UCL study (the group that both performed the alcohol memory cue exercise and received ketamine) showed the most significant reductions in alcohol use over time. But this group had a higher initial baseline rate of alcohol use than the other two groups (which, respectively, received psychological interventions plus placebo, and ketamine without a psychological intervention). 

    “Any benefits that were seen might therefore be a regression to the mean,” Dakwar cautioned. In other words, the heaviest-drinking group reduced their use to a level that was closer to the average of the other two groups.

    “But even assuming a real effect,” Dakwar added, “it may also suggest that the higher use at baseline was associated with greater distress regarding drinking, and that this group may have also been, consciously or not, more motivated to address their drinking.”

    In general, Dakwar warns that treatments narrowly focused on “rewriting” cognitive processes risk overlooking other social, emotional or psychological processes that influence people’s problematic drinking behaviors. The UCL researchers themselves indicated—that for ketamine to be useful for this purpose, a psychological framework with cognitive-behavioral approaches and other support may also necessary.



    Photo by Kelsey Chance on Unsplash

     

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