Promising Repurposing: FDA-Approved Drug Apremilast Shows Potential for Dual Relief in Alcohol Use Disorder & Chronic Pain
For millions struggling with Alcohol Use Disorder (AUD), the path too recovery is often complicated by chronic pain – a frequently overlooked factor that considerably increases the risk of relapse. Now, groundbreaking preclinical research from Scripps Research suggests a potential solution: repurposing an existing FDA-approved drug, apremilast, to concurrently address both alcohol intake and pain sensitivity. This discovery, published in JCI Insight on April 22, 2025, offers a hopeful new avenue for treating the complex interplay between addiction and pain.
The Overlooked Link Between alcohol, Pain, and Relapse
AUD affects an estimated 400 million people globally, according to the World health Institution. While treatment often focuses on curbing alcohol consumption, the presence of chronic pain is a powerful predictor of relapse. Many individuals with AUD experience a heightened sensitivity to touch – a condition known as mechanical allodynia – where even gentle pressure is perceived as painful. This pain can persist even during periods of abstinence, driving continued alcohol use as a form of self-medication.
“We’ve long understood the devastating cycle of pain and addiction,” explains Marisa Roberto,PhD,Professor of Neuroscience at Scripps research and senior author of the study. ”Our findings highlight the therapeutic value of apremilast in breaking that cycle, reducing both drinking and pain sensitivity in long-term abstinence - a critical component of triumphant recovery.”
Apremilast: from Skin Conditions to Addiction Treatment?
Apremilast is currently FDA-approved for the treatment of psoriasis and psoriatic arthritis, both inflammatory conditions.It works by inhibiting phosphodiesterase-4 (PDE4),an enzyme involved in inflammation. Previous research had already demonstrated apremilast’s ability to reduce alcohol consumption in both animal models and human trials. This new study expands on that knowledge,investigating its potential to alleviate pain associated with alcohol exposure.Key Findings from the Scripps Research Study
Researchers conducted experiments using two strains of rats – one genetically predisposed to higher alcohol consumption and a standard strain - giving them access to alcohol while administering either apremilast or a placebo. The results were compelling:
Reduced Alcohol intake: Apremilast significantly reduced alcohol consumption across both rat strains and in both males and females.
Decreased Pain Sensitivity: The drug demonstrably decreased pain sensitivity, both immediately after drinking and during abstinence periods ranging from 24 hours to four weeks.
Sex and Strain Specificity: Interestingly, the effects weren’t uniform. Pain relief wasn’t observed in all male rats, and the impact on brain signaling varied between strains, highlighting the importance of considering biological sex and genetic background in future research.
GABAergic Transmission Boost: Apremilast increased GABAergic transmission in the central amygdala – a brain region crucial for both addiction and pain regulation. This effect was primarily observed in the standard strain of rats.
Inflammation & PDE4 Expression: Alcohol exposure was found to increase the expression of PDE4 genes in the brain, further solidifying the link between inflammation, pain, and compulsive alcohol use.
Why This Matters: A Path Towards Personalized Therapies
The study’s findings suggest that apremilast could offer a novel, dual-action therapy for AUD, particularly for individuals experiencing pain during and after alcohol use. While other PDE4 inhibitors have been explored for pain management, apremilast’s existing FDA approval and demonstrated effect on alcohol consumption make it a particularly promising candidate.
“This isn’t a one-size-fits-all solution,” emphasizes Bryan Cruz,a postdoctoral fellow at Scripps Research and first author of the study. “The differences we observed based on sex and strain underscore the need for personalized approaches to treatment.Understanding why these differences exist will be crucial for maximizing the drug’s effectiveness.”
Looking Ahead: Addressing Emotional Distress & Clinical trials
The Scripps Research team is now focusing on investigating whether apremilast can also mitigate anxiety and other negative emotional states that often accompany alcohol withdrawal.
“Withdrawal-induced anxiety is a major driver of relapse,” explains Roberto. “Addressing the emotional component of addiction,alongside physical pain,is critical for long-term recovery. Many individuals turn to alcohol to cope with both physical and emotional distress.”
Ultimately, the researchers stress that clinical trials are necessary to confirm apremilast’s efficacy and safety in humans with AUD and co-occurring pain. However, this preclinical research provides a strong foundation for future examination and offers a beacon of hope for a more comprehensive and effective approach to treating this complex disorder.
Sources:
Cruz, B. et al. (2025). Apremilast reduces alcohol drinking
