The FDA-approved drug apremilast suppresses alcohol intake: clinical and pre-clinical validation

Treatment options for Alcohol Use Disorders (AUD) have minimally advanced since 2004, while the annual deaths and economic toll have become alarmingly high. Bringing potential therapeutics beyond the bench and into the clinic for AUD requires rigorous pharmacological screening across molecular, behavioral, pre-clinical, and clinical studies in neuroscience. The repurposing of FDA-approved compounds is an effective and expedited means of screening pharmacotherapies for AUD. Here, we demonstrate that apremilast, a phosphodiesterase type 4 inhibitor that is FDA approved for psoriasis and psoriatic arthritis, reduces binge-like alcohol intake and behavioral measures of motivation in unique, preclinical genetic risk models for drinking to intoxication and reduces excessive alcohol drinking in models of stress-facilitated drinking and alcohol dependence. In a double blind, placebo-controlled human laboratory study in non-treatment seeking individuals with AUD, apremilast significantly reduced the number of drinks per day. Lastly, using site-directed drug infusions and electrophysiology we determined that apremilast may act by increasing neural activity in the nucleus accumbens, an important alcohol-related brain region, to reduce alcohol intake in mice. These results demonstrate that apremilast reduces excessive alcohol drinking across a spectrum of AUD severity and support its importance as a potential therapeutic for AUD.