RT Journal Article SR Electronic T1 The FDA-approved drug apremilast suppresses alcohol intake: clinical and pre-clinical validation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.13.444033 DO 10.1101/2021.05.13.444033 A1 Kolter B. Grigsby A1 Regina A. Mangieri A1 Amanda J. Roberts A1 Marcelo F. Lopez A1 Alexander Tran A1 Evan J. Firsick A1 Kayla G. Townsley A1 Alan Beneze A1 Jessica Bess A1 Toby K. Eisenstein A1 Joseph J. Meissler A1 John M. Light A1 Jenny Miller A1 Susan Quello A1 Farhad Shadan A1 Michael Skinner A1 Heather C. Aziz A1 Pamela Metten A1 Richard A. Morissett A1 John C. Crabbe A1 Marisa Roberto A1 Howard C. Becker A1 Barbara J. Mason A1 Angela R. Ozburn YR 2021 UL http://biorxiv.org/content/early/2021/05/15/2021.05.13.444033.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.