Antibiotic Cuts Alcohol Cravings, May Enhance Psychotherapy

Liam Davenport

May 20, 2015

An antibiotic typically used to treat tuberculosis reduces alcohol cravings and may enhance cue-related extinction therapies in individuals with alcohol use disorders, new research shows.

The study, which was funded by the National Institutes of Health, showed that low doses of D-cycloserine significantly reduce alcohol cravings for up to 3 weeks, leading to significant reductions in alcohol consumption.

The researchers believe that the drug could also be used to enhance the effect of psychotherapies, such as cognitive-behavioral therapy (CBT), to provide a more durable outcome.

"We're trying to turn up the gas on this CBT intervention that focuses on helping people cope with their cravings better," lead author James MacKillop, PhD, Peter Boris Center for Addictions Research, McMaster University, Hamilton, Ontario, Canada, told Medscape Medical News.

"What we're trying to take are the most critical points in treatment and try to tune up the brain's responsiveness to those points to ultimately not just affect the person the most but lead to new learning that will be more robust over time and improve outcomes," Dr. MacKillop added.

The study was published online April 7 in Translational Psychiatry.

Unique Approach

D-cycloserine is the dextrorotary form of cycloserine and is a partial agonist of N-methyl-D-aspartate receptors, which play a central role in memory and learning.

To examine whether the drug could accelerate the extinction of cue-elicited craving for alcohol, the team studied individuals with alcohol use disorders who were seeking alcohol treatment and had evidence of reacting to alcohol cues.

Participants underwent an alcohol extinction paradigm, given as four sessions of manualized motivational enhancement therapy akin to cue exposure therapy, over 2 weeks in a naturalistic bar laboratory environment.

For sessions 1 and 3, which took place 1 week apart, the participants received D-cycloserine, 50 mg (n = 16), or placebo (n = 14) 1 hour beforehand. Follow-up cue reactivity sessions were then conducted 1 week and 3 weeks later.

At study outset, participants had significant and robust alcohol cue reactivity, with no significant differences between the two groups.

Those who received the study medication had significant reductions in alcohol craving and significant increases in extinction during the first session compared with those given placebo (P ≤ .05 for both). The significant impact of D-cycloserine on alcohol cravings was maintained at week 3 (P ≤ .05).

At the end of the study, participants who received the medication reported significantly fewer drinks per day, lower percentage of drinking days, and lower percentage of heavy drinking days (P ≤ .05, P ≤ .05, and P ≤ .01, respectively). However, these effects were no longer significant at the 3-week follow-up.

Minimal adverse effects occurred with the study drug. The only notable effect was a nonsignificant increase in drowsiness after the second administration.

Dr MacKillop noted that the low doses of D-cycloserine were used because, if the drug is given at the kinds of doses recommended for tuberculosis or chronically, it has paradoxical effects in terms of learning.

"This is a medication that would be given strategically on a small number of occasions, more than the two that we did in the study most likely, but nonetheless on a small number of occasions at specific points in treatment to try to accelerate the learning that's happening during the sessions," he said.

Summarizing the value of the research, Dr MacKillop said it focuses less on how the medication can change the body in a way that makes it less responsive to alcohol and more on how it can speed up and enhance the CBT processing to improve psychological treatment.

"It was a unique example of our employing a translational approach in which we took the naturalistic bar laboratory and combined it with a treatment protocol so that we could do both experimental research and clinical research at the same," he said.

"I think that that was something that is not typically done, and provides further evidence that perhaps we need to blur those lines between experimental research and clinical research more."

Confirmatory Findings

Commenting on the findings for Medscape Medical News, Mark Egli, PhD, program director of the Division of Neuroscience and Behavior at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, noted that D-cycloserine has been investigated over several decades for its effects on memory and learning.

Its desensitizing effect in patients with fearful responses to stimuli and, consequently, its potential as an extinction-type therapy led to its being studied for addiction, including to cocaine and nicotine.

"One of the important things about this approach is that D-cycloserine is something that's already used as an antibiotic, and could be administered to humans," Dr Egli explained to Medscape Medical News.

"So, unlike many of the preclinical animal studies that we support with drugs that are not approved for human use, we can readily confirm findings in the laboratory sooner with a drug like this."

For Dr Egli, the importance of D-cycloserine is not that it's necessarily a new concept or a new drug but that it confirms earlier findings with alcohol, thus making it a "legitimate target" for further basic research studies.

Furthermore, it provides information on the effective dosing parameters, as well as cue extinction parameters.

"I think that lends some clarity to some of the discordant findings previously, [and] that sets the stage for larger studies and potentially studies with new drugs that have similar types of mechanisms but may be more efficacious," Dr Egli observed.

"I think in the future, you could explore ways to combine this intervention with additional pharmacotherapies or cognitive behavioral therapies," he added.

Acknowledging the lack of persistent effect with D-cycloserine, Dr Egli said that the findings show "that this drug is not going to be a big new blockbuster or anything of that sort...because it's been around for so long."

"I think if it was going to be a big new approach clinically for treating these things, we would have known that by now."

This study was supported by National Institutes of Health grants. Dr MacKillop is the holder of the Peter Boris Chair in Addictions Research, which partially supported his contributions. A coauthor is a member of the Advisory Board of D&A Pharma and has received travel expenses and honoraria from this company. He has received consulting fees from Transcept Pharmaceuticals and Pharmaceutico CT. The remaining authors have disclosed no relevant financial relationships.

Translat Psychiatry. Published online April 7, 2015. Abstract

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