Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases.

There exists a substantial need to identify new neuropharmacological targets to treat alcohol-dependent individuals. Ghrelin represents a gut-brain peptide, initially discovered as the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The existing literature clearly demonstrates that ghrelin affects appetite and food intake. Both animal and human studies provide evidence that ghrelin not only influences hunger but also has a role in the search for rewarding substances, such as alcohol. Animal studies provide evidence that ghrelin stimulates the reward system, acting on specific brain reward nodes, and that ghrelin signaling is required for stimulation of the reward system by alcohol. Human studies show that ethanol acutely affects ghrelin levels. Interestingly, human studies with alcohol-dependent individuals suggest that higher ghrelin levels are associated with higher self-reported measurements of alcohol craving. Altogether, these findings suggest that the ghrelin system plays a role in alcohol dependence. Ghrelin antagonists (i.e., GHS-R1a antagonists and/or inverse agonists) might affect alcohol-seeking behavior, thus having therapeutic potential in alcohol use disorders. Future laboratory and clinical studies testing this hypothesis are warranted.