Understanding the link between pharmacological manipulation of the ghrelin system and alcohol hangover symptoms: Results from two human laboratory studies

Authors

• M Farokhnia
• MR Lee
• LA Farinelli
• VA Ramchandani
• F Akhlaghi
• L Leggio

Abstract

Ghrelin is an orexigenic peptide primarily synthesized in the stomach, which regulates food intake and energy homeostasis. Ghrelin has also been shown to modulate neural substrates of alcohol-seeking behaviors. Alcohol consumption frequently results in hangover symptoms, a largely underexplored phenomenon with considerable medical and socioeconomic consequences. Mechanisms involved in the pathophysiology of hangover considerably overlap with ghrelin’s physiological functions. Here, we investigated whether pharmacological manipulations of the ghrelin system may affect alcohol-related hangover. Data were obtained from two placebo-controlled laboratory studies. The first study tested the effects of intravenous (IV) ghrelin and consisted of two experiments: a progressive-ratio IV alcohol self-administration (IV-ASA) and a fixed-dose IV alcohol clamp. The second study tested an oral ghrelin receptor inverse agonist (PF-5190457) in combination with fixed-dose oral alcohol administration. In both studies, alcohol hangover data were collected the morning after each alcohol administration procedure using the Acute Hangover Scale (AHS). IV ghrelin compared to placebo significantly reduced the AHS mean score after IV-ASA (p=0.04) and alcohol clamp (p=0.04) experiments; PF-5190457 had no significant effect on AHS scores. Females reported significantly higher hangover symptoms than males (p=0.04), but no gender × drug condition (ghrelin vs. placebo) effect was found. AHS mean scores were positively correlated with peak alcohol ‘sedation’ (p=0.009), ‘feel high’ (p=0.05), and ‘feel intoxicated’ (p=0.03) during the IV-ASA. This is the first study showing that exogenous ghrelin administration, but not ghrelin receptor inverse agonism, affects hangover symptoms. Future research should investigate the potential mechanism(s) underlying this effect.

Scientific Focus Area: Neuroscience

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