The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study.

Rodent studies indicate that ghrelin receptor blockade reduces alcohol consumption. However, no ghrelin receptor blockers have been administered to heavy alcohol drinking individuals. Therefore, we evaluated the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and behavioral effects of a novel ghrelin receptor inverse agonist, PF-5190457, when co-administered with alcohol.

Effect of Functionally Significant Deiodinase Single Nucleotide Polymorphisms on Drinking Behavior in Alcohol Dependence: An Exploratory Investigation.

Background: Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism; however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence. The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes: D1, D2, and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNPs) of these deiodinase genes may play a role in HPT dysfunction.

Fasting-induced increase in plasma ghrelin is blunted by intravenous alcohol administration: a within-subject placebo-controlled study.

Ghrelin is a 28-amino acid peptide produced mainly by mucosal neuroendocrine cells lining the fundus of the stomach. Preclinical and clinical studies suggest that ghrelin plays a role in alcoholism. Furthermore, human laboratory studies indicate that acute oral administration of alcohol results in reduced circulating ghrelin.