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LA JOLLA, CA – A drug already approved by the U.S. Food and Drug Administration (FDA) to treat inflammatory conditions like psoriasis may hold potential for tackling two significant challenges often faced by individuals with alcohol use disorder (AUD): high alcohol consumption and increased pain sensitivity, according to a new preclinical study.
Research led by scientists at Scripps Research, published on April 22, 2025, in the journal JCI Insight, indicates that apremilast could serve as a dual-purpose therapy. Apremilast is a phosphodiesterase-4 (PDE4) inhibitor, meaning it blocks an enzyme involved in the body’s inflammatory processes.
The study highlights apremilast’s potential benefit, particularly for individuals with AUD who experience chronic pain, both while consuming alcohol and during the difficult recovery period. Chronic pain is recognized as a major hurdle in AUD recovery, significantly increasing the risk of relapse, yet it is frequently unaddressed in current treatment approaches. Many individuals with AUD also suffer from mechanical allodynia, a condition where normally non-painful touch is perceived as painful, which can persist even during abstinence.
“Our findings highlight the therapeutic value of apremilast to reduce co-occurring drinking and mechanical allodynia in long-term abstinence—a critical component of harmful drinking and AUD psychopathology,” stated senior author Marisa Roberto, PhD, a professor of neuroscience at Scripps Research.
Globally, the World Health Organization estimates that around 400 million people aged 15 and older suffer from AUD.
This new research builds upon previous findings that showed apremilast could reduce alcohol drinking in both animal models and humans. The latest study specifically investigated whether the drug could also alleviate the pain sensitivity often linked to alcohol exposure.
The research team used two different rat strains – one genetically selected for higher alcohol consumption and a standard strain – to test apremilast against a placebo. Both male and female rats were included.
The results showed that apremilast significantly decreased alcohol intake across both strains and sexes. Furthermore, it reduced pain sensitivity (allodynia) in most groups tested, not only shortly after drinking but also during periods of abstinence lasting from 24 hours up to four weeks.
However, the researchers noted important nuances. “At specific time points, the patterns of reduction differed between males and females, as well as between strains,” observed first author Bryan Cruz, PhD, a postdoctoral fellow at Scripps Research. For instance, the pain-reducing effects were not seen in some male rat groups, emphasizing the need for future studies to carefully consider biological sex differences.
Investigating the underlying mechanisms, the team found that apremilast boosted inhibitory brain signaling (specifically GABAergic transmission) in the central amygdala – a brain region critical for processing both addiction and pain. Interestingly, this effect was only observed in the standard rat strain, suggesting that genetic factors or inherent vulnerability to AUD might influence how the drug works in the brain. The study also found that alcohol exposure increased the expression of PDE4 genes in the brains of male rats from both strains, reinforcing the connection between inflammation, pain, and compulsive alcohol use.
While other PDE4 inhibitors have been explored for pain management unrelated to alcohol, apremilast’s existing FDA approval and these findings suggest a potential pathway toward more personalized treatments for the challenging combination of AUD and pain.
Looking ahead, the Scripps Research team plans to investigate whether apremilast could also alleviate other common withdrawal symptoms, such as anxiety and negative emotional states. “Addressing other key components of the addiction cycle is critical, as many individuals use alcohol to cope not only with physical pain but with emotional distress as well,” Professor Roberto noted.
Clinical research in humans will be necessary to confirm apremilast’s effectiveness and safety for treating AUD and associated pain.
Disclaimer: This article reports on findings from a preclinical study conducted in animal models. While promising, these results may not directly translate to humans. Further research, including extensive clinical trials, is required to determine the safety and efficacy of apremilast for treating alcohol use disorder and associated pain in people.
