Summary: Apremilast, an FDA-approved drug for treating skin conditions including psoriasis and psoriatic arthritis, triggers increased activity in the nucleus accumbens, an area of the brain associated with regulating alcohol consumption. Apremilast reduced alcohol drinking behaviors in model mice at genetic risk for alcohol use disorder.
Source: Oregon Health and Science University
Researchers from Oregon Health & Science University and institutions across the country have identified a pill used to treat a common skin condition as an “incredibly promising” treatment for alcohol use disorder.
The study has just been published in the Clinical Investigation Journal.
On average, people who received the drug, called apremilast, cut their alcohol consumption by more than half, 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.
Funding: The research reported here was supported by National Institutes of Health Awards AA016651, AA013519, AA010760, AA07468, AA027692, U01 AA013498, DA013429, P60AA06420, and U01AA025476; the US Department of Veterans Affairs awards BX000313, BX004699, and IK2 BX002488; and a gift from the John R. Andrews family. The contents are the sole responsibility of the researchers and do not necessarily represent the official views of the NIH or the United States Department of Veterans Affairs.
About this news on research in psychopharmacology and addiction
Author: Eric Robinson
Source: Oregon Health and Science University
Contact; Erik Robinson – Oregon Health and Science University
Picture: Image is in public domain
See also
Original research: Free access.
“Preclinical and clinical evidence for the suppression of alcohol consumption by apremilast” by Angela Ozburn et al. Clinical Investigation Journal
Abstract
Preclinical and clinical evidence for the suppression of alcohol consumption by apremilast
Treatment options for alcohol use disorder (AUD) have advanced little since 2004, while annual deaths and the economic toll have increased alarmingly. Phosphodiesterase type 4 (PDE4) is associated with alcohol and nicotine dependence. PDE4 inhibitors have been identified as a potential treatment for AUD using a novel bioinformatics approach.
We prioritized a novel PDE4 inhibitor, apremilast, ideal for reuse (i.e. FDA approved for psoriasis, low incidence of adverse events, excellent safety profile) and have tested it on several strains and animal models, as well as a human Phase IIa study.
We found that apremilast reduced binge drinking and behavioral measures of alcohol motivation in mouse models of genetic risk of alcohol consumption leading to intoxication. Apremilast also reduced binge drinking in models of stress-facilitated drinking and alcohol dependence.
Using site-directed drug infusions and electrophysiology, we found that apremilast may act to reduce alcohol consumption in mice by increasing neuronal activity in the nucleus accumbens, a region key brain in the regulation of alcohol consumption. Importantly, apremilast (90 mg/d) reduced excessive alcohol consumption in people with AUD who did not seek treatment in a double-blind, placebo-controlled study.
These results demonstrate that apremilast suppresses excessive alcohol consumption across the spectrum of AUD severity.