PT  - JOURNAL ARTICLE
AU  - Kolter B. Grigsby
AU  - Regina A. Mangieri
AU  - Amanda J. Roberts
AU  - Marcelo F. Lopez
AU  - Alexander Tran
AU  - Evan J. Firsick
AU  - Kayla G. Townsley
AU  - Alan Beneze
AU  - Jessica Bess
AU  - Toby K. Eisenstein
AU  - Joseph J. Meissler
AU  - John M. Light
AU  - Jenny Miller
AU  - Susan Quello
AU  - Farhad Shadan
AU  - Michael Skinner
AU  - Heather C. Aziz
AU  - Pamela Metten
AU  - Richard A. Morissett
AU  - John C. Crabbe
AU  - Marisa Roberto
AU  - Howard C. Becker
AU  - Barbara J. Mason
AU  - Angela R. Ozburn
TI  - The FDA-approved drug apremilast suppresses alcohol intake: clinical and pre-clinical validation
AID  - 10.1101/2021.05.13.444033
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.13.444033
4099  - http://biorxiv.org/content/early/2021/05/15/2021.05.13.444033.short
4100  - http://biorxiv.org/content/early/2021/05/15/2021.05.13.444033.full
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.