Commentary: Preclinical and Clinical Evidence for Suppression of Alcohol Intake by Apremilast

A recently published article in the Journal of Clinical Investigation demonstrated that apremilast, a commonly used drug to treat psoriasis, is associated with reduced excessive alcohol drinking in models of stress-facilitated drinking and alcohol dependence.¹ These findings may have major implications regarding the treatment of psoriasis, where there is a clear link between disease and alcohol use,^2,3 and where apremilast is frequently used for treatment.⁴

Genetic variants in the PDE4B gene locus have been implicated with both alcohol and nicotine dependence in a genome-wide association study,⁵ and another PDE4 inhibitor, rolipram, has been shown to dose-dependently reduce self-administration of alcohol in a mouse model of alcohol consumption.⁶ PDE4 is expressed in the central nervous system, in the nucleus accumbens, a brain region associated with motivation and emotional processes.⁷ In the study highlighted here, the authors set out to determine if apremilast, a PD4 inhibitor, affects alcohol consumption in both mouse models of alcohol drinking and a double-blind, placebo-controlled proof-of-concept study in a moderate-size cohort composed of 24 women and 27 men, with a history of heavy drinking for an average ten years prior to the study. The findings demonstrated that apremilast reduced the number of drinks per day relative to the placebo and the probability of a heavy drinking day.¹ The group further showed that apremilast alters the intrinsic excitability of nucleus accumbens-derived neurons expressing dopamine receptor D1, providing a mechanistic basis for its effect on alcohol consumption.¹

Alcohol use disorder is frequent in patients with psoriasis and found in up to 8.6% of patients with psoriasis,² and up to 23.8% of been reported to be high-risk drinkers.³ Furthermore, alcohol consumption has been shown to correlate with psoriasis severity.² This also could relate to weight loss mechanisms in psoriasis, which principally relates to decreased abdominal subcutaneous fat, independent of its effect on psoriatic disease activity.⁸ Thus, the implications of this study on psoriasis management could be substantial and may help guide treatment in psoriasis patients with concomitant addiction problems. However, this will need to be confirmed and validated in future studies.