Researchers find immune system drug can dramatically reduce alcohol consumption

man pouring drugs into hand medicine aspirin

Otezla® is a prescription medicine used to treat moderate to severe plaque psoriasis in adults. It works by inhibiting an enzyme called phosphodiesterase 4 (PDE4), which is involved in inflammation. It is important to note that this medication is not approved for the treatment of alcohol use disorders and further research is needed to determine its effectiveness and safety in this population. It is also important to consult with a health care provider before taking any medication to treat alcohol use disorder.

Researchers from Scripps Research have found that apremilast (Otezla®) can reduce alcohol consumption by more than 50% in people with severe alcohol use disorder.

A clinical trial conducted by the Scripps Research Institute found that apremilast, an FDA-approved drug for the treatment of psoriasis, significantly reduced alcohol consumption by more than 50% in people with severe psoriasis-related disorders. alcohol consumption (AUD). Additionally, researchers at Oregon Health and Science University (OHSU) and other institutions have found that in mice, apremilast increases activity in a brain region known to play a role in AUD.

The research was recently published in the Clinical Investigation Journal.

“We are incredibly thrilled to have found a drug that has such a strong effect on alcohol consumption, and with such good tolerability and safety at the same time,” says co-lead author Barbara Mason, Ph.D. , the Pearson Family Chairman and Director of the Pearson Center for Alcohol and Addiction Research at Scripps Research.

About 29.5 million Americans meet the criteria for AUD, which encompasses the conditions known as alcohol abuse, alcohol dependence, and alcohol dependence. Less than 10% of people with this disorder receive treatment, and an even smaller number are prescribed medication to treat AUD.

Mason is the Translational Opportunities Group Director for the Integrative Neuroscience Initiative on Alcoholism-NeuroImmune (INIA-NeuroImmune), a multidisciplinary collaborative consortium funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to study the underlying biology of alcohol consumption. mess. In his role at INIA-NeuroImmune, Mason reviews research conducted by the consortium’s basic scientists, then identifies the most promising drug candidates for clinical trials.

INIA-NeuroImmune collaborators have identified apremilast, sold under the brand name Otezla®, as a drug with the potential to treat AUD. The drug was known to block a molecule known as PDE4, which plays an important role in immune and brain cell function. While its use in the treatment of psoriasis is due to its immune function, basic science studies in mice had suggested that blocking PDE4 in the brain could reduce alcohol consumption.

Mason initiated a Phase 2 trial, conducted entirely at Scripps Research’s Pearson Center for Alcoholism and Addiction Research, to study apremilast in humans. Of the PDE4 inhibitor drugs available, Mason chose apremilast because it had fewer gastrointestinal side effects associated with earlier PDE4 inhibitors such as rolipram or ibudilast. The trial recruited 51 paid adult volunteers with severe AUD, none of whom were actively trying to reduce alcohol consumption. For 14 days, each person took a daily pill of apremilast or a placebo.

On average, participants consumed about five alcoholic beverages a day at the start of the study. People who received the placebo still drank nearly five drinks a day, while those taking apremilast reduced their alcohol intake to only about two drinks a day. In addition, apremilast decreased the percentage of days on which participants were classified as ‘heavy drinkers’. People who took apremilast reported anecdotally that they felt little urge to drink and did not have the desire for alcohol that they usually had. Additionally, the drug was well tolerated, with no participants discontinuing treatment due to gastrointestinal side effects.

“In this study, we saw that apremilast worked in mice. It worked in different labs, and it worked in people. It’s incredibly promising for addiction treatment in general,” says co-lead author Angela Ozburn, Ph.D., associate professor of behavioral neuroscience at OHSU School of Medicine and research biologist at Portland. VA Health Care System.

“Even with currently FDA-approved drugs for alcohol use disorder, we generally see smaller effects,” Mason says. “It is very unusual to get results like this, especially in a severely affected population. It will now have to move on to larger and broader clinical trials, but with this study, I think we have shown that this is an incredibly promising drug for alcohol use disorder.

Reference: “Preclinical and clinical evidence for the suppression of alcohol consumption by apremilast” by Kolter B. Grigsby, Regina A. Mangieri, Amanda J. Roberts, Marcelo F. Lopez, Evan J. Firsick, Kayla G. Townsley, Alan Beneze, Jessica Bess, Toby K. Eisenstein, Joseph J. Meissler, John M. Light, Jenny Miller, Susan Quello, Farhad Shadan, Michael H. Skinner, Heather C. Aziz, Pamela Metten, Richard A. Morissett, John C. Crabbe, Marisa Roberto, Howard C. Becker, Barbara J. Mason, and Angela R. Ozburn, January 19, 2023, Clinical Investigation Journal.
DOI: 10.1172/JCI159103

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