Role of the ‘hunger hormone’ ghrelin in alcohol dependence

2017

Challenge

Development of treatments for alcohol use disorder requires understanding the brain and body signaling systems that control alcohol drinking. Preclinical evidence suggests that ghrelin, a peptide hormone synthesized in the stomach that is integral to communication between the gut and brain, influences alcohol consumption by modulating the brain’s reward and stress pathways. However, whether and how ghrelin impacts alcohol intake in humans is unclear.

Advance

IRP researchers led by Lorenzo Leggio, M.D., performed the first-ever double-blind, placebo-controlled human laboratory study designed to investigate the effects of intravenous (IV) ghrelin administration on alcohol self-administration in heavy-drinking individuals with alcohol dependence. Compared to a placebo, ghrelin increased alcohol self-administration in the presence of alcohol cues, as well as activation of the amygdala, a part of the brain known to be involved in alcohol-seeking behavior.

Impact

These findings indicate that ghrelin is a key component of the gut-brain axis that contributes to alcohol drinking and shed light on the neurobiological mechanisms by which it does so. Treatments that target ghrelin production and/or signaling may be promising targets for development of novel medications to treat alcohol use disorder.

Publications

Farokhnia M, Grodin EN, Lee MR, Oot EN, Blackburn AN, Stangl BL, Schwandt ML, Farinelli LA, Momenan R, Ramchandani VA, and Leggio L. (2017). Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Molecular Psychiatry. 10.1038/mp.2017.226.