A new preclinical study from Scripps Research suggests that a drug already approved by the U.S. Food and Drug Administration (FDA) for treating inflammation could help reduce both alcohol intake and pain sensitivity — two issues that often occur together in people with alcohol use disorder (AUD).
The study, published on April 22, 2025, in the journal JCI Insight, focused on apremilast, a medication currently used to treat psoriasis and psoriatic arthritis. Apremilast works by blocking an enzyme involved in inflammation called phosphodiesterase-4 (PDE4).
The researchers found that this drug may have a dual purpose: it may help people with AUD both reduce their alcohol consumption and manage the pain that often comes with the condition.
AUD affects around 400 million people worldwide, according to the World Health Organization. Chronic pain is a major factor that can lead to alcohol relapse, but it’s not always addressed in current treatment approaches.
Many people with AUD experience a condition known as mechanical allodynia — a heightened pain response where even light touch can feel painful. This can continue during periods of abstinence and contribute to relapse.
“Our findings highlight the therapeutic value of apremilast to reduce both drinking and pain during abstinence,” said senior author Marisa Roberto, professor of neuroscience at Scripps Research. “This is a critical step toward better treatment for AUD.”
The team studied the effects of apremilast in two types of rats: one strain that is genetically more likely to drink alcohol, and another standard strain. Both groups had access to alcohol and were given either apremilast or a placebo.
The results showed that apremilast significantly reduced alcohol intake in both male and female rats across both strains. It also reduced pain sensitivity, both immediately after drinking and for up to four weeks after alcohol was removed.
However, the effects weren’t the same across all groups. “At specific time points, we saw differences in how apremilast worked depending on the rat’s sex and genetic background,” explained lead author Bryan Cruz, a postdoctoral fellow at Scripps Research.
For example, some male rats didn’t experience the same pain relief, which suggests that biological sex may play a role in how the drug works.
Further experiments revealed that apremilast increased a type of brain signaling called GABAergic transmission in the central amygdala — a region of the brain involved in both addiction and pain.
This increase in inhibitory signaling may help explain how the drug eases stress and discomfort. Interestingly, this effect was only observed in the standard strain of rats, which suggests that genetic background may influence how apremilast works in the brain.
In both rat strains, alcohol exposure increased the activity of PDE4 genes in the brain. This finding further supports the idea that inflammation may be linked to both pain and compulsive alcohol use.
While other PDE4 inhibitors have been studied for pain management unrelated to alcohol, apremilast may offer a targeted treatment option for people dealing with both AUD and chronic pain. More research is needed to test whether the drug is effective in humans.
Looking ahead, the research team plans to study whether apremilast can also reduce anxiety and emotional distress during alcohol withdrawal. “We know that anxiety during withdrawal is a major reason people relapse,” said Roberto. “Treating the emotional and physical symptoms of withdrawal could make recovery more achievable for many people.”
If you care about pain, please read studies about Scientists find a new way to manage knee pain and findings of Promising new drug offers hope for chronic nerve pain relief.
For more information about pain, please read studies about Chronic morphine use for cancer pain may increase bone loss and findings of Scientists find a new hope for chronic pain.
The study is published in JCI Insight.
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