Anti-Inflammatory Drug Tackles Alcohol Addiction and Pain

A common anti-inflammatory medication may offer new hope for the millions worldwide struggling with alcohol addiction and related pain sensitivities, according to research published Tuesday in JCI Insight.

Scientists at Scripps Research have discovered that apremilast—a drug already FDA-approved for treating psoriasis and psoriatic arthritis—shows promise in addressing both excessive drinking and the heightened pain sensitivity that often accompanies alcohol use disorder (AUD).

The study found that apremilast reduced alcohol consumption across different genetic strains of rats, regardless of biological sex. More surprisingly, it also decreased pain sensitivity during active drinking periods and throughout abstinence—from 24 hours to as long as four weeks after alcohol removal.

“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,” says senior author Marisa Roberto, a professor of neuroscience at Scripps Research.

AUD affects an estimated 400 million people aged 15 years or older globally, according to World Health Organization figures cited in the study. Many individuals with alcohol addiction experience mechanical allodynia—a condition where even light touch feels painful—which can persist during abstinence and drive continued drinking.

The research team tested apremilast in both specially bred rats with genetic predispositions to higher alcohol consumption and standard laboratory rats. The medication’s effects varied somewhat by sex and genetic background, with some male rats showing different responses to the treatment’s pain-relieving properties.

Notably, the scientists observed that apremilast increased inhibitory brain signaling in the central amygdala—a region implicated in both addiction and pain processing—but only in one strain of rats. This suggests the drug’s effectiveness may depend partly on genetic factors or individual vulnerability to AUD.

The study builds on previous research showing apremilast reduced alcohol consumption in both mice and humans. As a phosphodiesterase-4 (PDE4) inhibitor, the drug blocks an enzyme involved in inflammation, which may explain its dual action on drinking behavior and pain sensitivity.

Bryan Cruz, a postdoctoral fellow at Scripps Research and first author of the study, noted that “the patterns of reduction differed between males and females, as well as between strains,” highlighting the importance of considering biological sex in future investigations.

In both strains of male rats, alcohol exposure increased expression of PDE4 genes in the brain, providing further evidence of a link between inflammation, pain and compulsive alcohol use.

While the results are promising, clinical research is still needed to determine the drug’s efficacy for treating co-occurring AUD and pain in humans. The team plans to explore whether apremilast might also help address the anxiety and emotional distress that commonly emerge during alcohol withdrawal.

“For over a decade, it’s been well-established that withdrawal-induced anxiety is a major driver of relapse,” Roberto points out. “Therefore, 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.”

This dual-action approach could potentially transform treatment options for the millions struggling with alcohol addiction and its painful physical consequences.