Researchers Discover That Immune System Drug Can Significantly 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 medicine is not approved for the treatment of alcohol use disorder, and more research is needed to determine its effectiveness and safety in this population. It is also important to consult a healthcare provider before taking any medication to treat alcohol use disorder.

Researchers at Scripps Research discovered that apremilast (Otezla®) can reduce alcohol consumption by over 50% in individuals with severe alcohol use disorder.

A clinical trial conducted by Scripps Research Institute has revealed that apremilast, an FDA-approved medication for the treatment of psoriasis, significantly reduces alcohol intake by over 50% in individuals with severe alcohol use disorder (AUD). In addition, researchers from Oregon Health and Science University (OHSU) and other institutions found that in mice, apremilast increases activity in a region of the brain known to play a role in AUD.

The research was recently published in the Journal of Clinical Investigation.

“We’re incredibly excited to have found a drug that has such a large effect size on alcohol consumption, and with such good tolerability and safety at the same time,” says co-senior author Barbara Mason, Ph.D., the Pearson Family Chair 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 addiction. Fewer than 10% of people with the disorder get any treatment, and an even smaller number are prescribed medication to treat AUD.

Mason is the director of the Translational Opportunities group 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 use disorder. In her role with INIA-NeuroImmune, Mason reviews research conducted by basic scientists in the consortium and then identifies the most promising drug candidates for clinical trials.

INIA-NeuroImmune collaborators pinpointed 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 important roles in both immune and brain cell function. While its use in treating psoriasis is due to its immune function, basic scientific studies in mice had suggested that blocking PDE4 in the brain could reduce alcohol intake.

Mason launched a phase 2 trial, carried out entirely at the Pearson Center for Alcoholism and Addiction Research at Scripps Research, to study apremilast in humans. Among available PDE4 inhibitor medications, Mason chose apremilast because it had fewer of the gastrointestinal side effects associated with earlier PDE4 inhibitors such as rolipram or ibudilast. The trial enrolled 51 paid adult volunteers with severe AUD, none of whom were actively trying to consume less alcohol. For 14 days, each person took a daily pill of either apremilast or a placebo.

On average, participants consumed about five alcoholic drinks per day at the start of the study. People who received the placebo still drank nearly five drinks each day, while those who took apremilast reduced their alcohol intake to only about two drinks per day. In addition, apremilast decreased the percentage of days that participants were classified as “heavy drinkers.” People who took apremilast reported anecdotally that they felt little impulse to drink and lacked the desire for alcohol that they usually had. Moreover, 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. This is incredibly promising for treatment of addiction in general,” says co-senior author Angela Ozburn, Ph.D., associate professor of behavioral neuroscience in the OHSU School of Medicine and a research biologist with the Portland VA Health Care System.

“Even with drugs currently approved by the FDA for alcohol use disorder, we usually see smaller effect sizes,” says Mason. “It’s very unusual to get results like this, particularly in a severely affected population. This will need to move to larger, broader clinical trials now, but with this study, I think we’ve shown that this is an incredibly promising drug for alcohol use disorder.”

Reference: “Pre-clinical and clinical evidence for suppression of alcohol intake 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, 19 January 2023, Journal of Clinical Investigation.
DOI: 10.1172/JCI159103

4 Comments on "Researchers Discover That Immune System Drug Can Significantly Reduce Alcohol Consumption"

  1. Eric M. Jones | March 5, 2023 at 10:45 am | Reply

    “Despite all we can say, many who are real alcoholics are not going to believe they are in that class. By every form of self- deception and experimentation, they will try to prove themselves exceptions to the rule, therefore non-alcoholic. If anyone who is showing inability to control his drinking can do the right-about- face and drink like a gentleman, our hats are off to him. Heaven knows, we have tried hard enough and long enough to drink like other people!”
    From the AA big book.

  2. Get the C19 vax. For a lot of people it reduces the consumption of everything to zero.

  3. This info litterally can be translated to .
    Ones immune system status dictates suceptability to alcoholism.
    And that.
    Is how it should read.

  4. Started Otezla less than a month ago. My alcohol consumption has dropped by 50% or more; and I have to remind myself to eat. No hunger pains, no cravings for anything specific.

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