A recent preclinical study from Scripps Research suggests that a drug approved by the FDA for inflammatory conditions might help in reducing both alcohol consumption and pain sensitivity, which are common issues with alcohol use disorder (AUD). The research highlights apremilast's potential as a dual-acting therapy for AUD, particularly beneficial for individuals experiencing pain during and after alcohol use. AUD affects a significant global population, and chronic pain is one of the strongest predictors of alcohol relapse, often overlooked in treatment strategies.

Therapeutic Benefits of Apremilast

This section explores how apremilast can serve as an effective treatment option for AUD and associated pain. According to the findings, apremilast reduces co-occurring drinking and mechanical allodynia in long-term abstinence, crucial components of harmful drinking and AUD psychopathology. Initially approved for treating psoriasis and psoriatic arthritis, apremilast has shown promise in reducing alcohol intake in both animal models and humans. The new study extends this understanding by examining its effects on pain linked to alcohol exposure.

The researchers tested apremilast on rats genetically predisposed to higher alcohol consumption and standard genetic strains. The results indicate that apremilast significantly diminishes alcohol intake across different rat strains and biological sexes. Additionally, it alleviates pain sensitivity in most groups, whether immediately after drinking or during abstinence periods ranging from 24 hours to four weeks post-alcohol removal. However, the patterns of reduction vary between males and females and among strains, emphasizing the importance of considering biological sex in future studies. For instance, some male rats did not exhibit the pain-relieving effects, highlighting the need for further investigation into these differences.

Neurobiological Mechanisms and Future Directions

This segment delves into the neurobiological mechanisms underlying apremilast's effects and outlines future research directions. In another set of experiments, apremilast increased inhibitory signaling that regulates pain and stress in the central amygdala, a brain region involved in addiction and pain. This effect was observed only in the standard strain of rats, suggesting that apremilast's impact on brain signaling may depend on genetic background or vulnerability to AUD. Moreover, alcohol exposure in male rats heightened the expression of PDE4 genes in the brain, reinforcing the connection between inflammation, pain, and compulsive alcohol use.

While other PDE4 inhibitors have been studied for pain unrelated to alcohol consumption, apremilast could pave the way for more personalized therapies addressing both AUD and pain. Clinical research remains necessary to ascertain the drug's efficacy in humans. Moving forward, the researchers aim to investigate whether apremilast can alleviate anxiety and other negative emotional states emerging during alcohol withdrawal. Addressing these key components of the addiction cycle is essential, as many individuals use alcohol to cope with physical pain and emotional distress. Thus, apremilast holds promise as a comprehensive therapeutic approach for AUD and related challenges.