Apremilast is a medicine used for the treatment of psoriatic arthritis, psoriasis and ankylosing spondylitis. It works by blocking the activity of an enzyme called phosphodiesterase 4 (PDE4), which helps reduce inflammation in the body.
A study conducted by OHSU and other research institutes nationwide has shown promising results for a new treatment for alcohol use disorders.
A team of researchers from Oregon Health & Science University and various institutions across the country have found a drug, commonly used to treat a skin condition, as a very promising treatment for alcohol use disorder.
The study has just been published in the Clinical Investigation Journal.
People who were treated with apremilast, on average, showed a decrease in their daily alcohol consumption by more than 50%, reducing their consumption from five drinks a day to two.
“I’ve never seen anything like this before,” said 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.
The lead author is Kolter Grigsby, Ph.D., postdoctoral fellow at OHSU’s Ozburn Laboratory.
Beginning in 2015, Ozburn and his collaborators searched a genetic database for compounds that may counteract the expression of genes known to be linked to heavy drinking. Apremilast, an FDA-approved anti-inflammatory drug used to treat psoriasis and psoriatic arthritis, seemed like a promising candidate.
They then tested it in two unique animal models with a genetic risk for heavy drinking, as well as other strains of mice in labs across the country. In each case, apremilast reduced alcohol consumption among a variety of models predisposed to light to heavy alcohol consumption. They found that apremilast triggered an increase in activity in the nucleus accumbens, the region of the brain involved in controlling alcohol consumption.
Researchers at the Scripps Research Institute in La Jolla, Calif., then tested apremilast in humans.
The Scripps team conducted a double-blind, placebo-controlled clinical proof-of-concept study involving 51 people who were evaluated for 11 days of treatment.
“The large effect size of Apremilast in reducing alcohol consumption, combined with its good tolerability in our participants, suggests that it is an excellent candidate for further evaluation as a new treatment for people with alcohol use disorders,” said co-lead author Barbara Mason, Ph.D., Pearson Family Professor in the Department of Molecular Medicine at Scripps.
The clinical study involved people with alcohol use disorders who were not seeking any form of treatment, and Mason predicts that apremilast may be even more effective in people who are motivated to reduce their alcohol consumption.
“It is imperative that more clinical trials be done on people seeking treatment,” Ozburn said. “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.
An estimated 95,000 people in the United States die each year from alcohol-related deaths, according to the National Institute on Alcohol Abuse and Alcoholism.
Currently, there are three drugs approved for alcohol use disorder in the United States: Antabuse, which produces an acute hangover-like sensitivity when alcohol is consumed; acamprosate, a drug believed to stabilize chemical signaling in the brain associated with relapse; and naltrexone, a drug that blocks the euphoric effects of alcohol and opioids.
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
The study was funded by the National Institutes of Health, the US Department of Veterans Affairs and the John R. Andrews family.