Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation

Biol Psychiatry. 2014 Nov 1;76(9):734-41. doi: 10.1016/j.biopsych.2014.03.019. Epub 2014 Mar 25.

Abstract

Background: There is a need to identify novel pharmacologic targets to treat alcoholism. Animal and human studies suggest a role for ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving.

Methods: This was a double-blind, placebo-controlled human laboratory proof-of-concept study. Nontreatment-seeking, alcohol-dependent, heavy-drinking individuals were randomized to receive intravenous ghrelin 1 mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cue-reactivity procedure, during which participants were exposed to neutral (juice) and alcohol cues. The primary outcome variable was the increase in alcohol craving (also called urge) for alcohol, assessed by the Alcohol Visual Analogue Scale.

Results: Out of 103 screenings, 45 individuals received the study drug. Repeated measures of analysis of covariance revealed a group effect across ghrelin doses in increasing alcohol craving (p < .05). A dose-specific examination revealed a significant effect of ghrelin 3 mcg/kg versus placebo in increasing alcohol craving (p < .05) with a large effect size (d = .94). By contrast, no significant ghrelin effect was found in increasing either urge to drink juice or food craving (p = ns). No significant differences in side effects were found (p = ns).

Conclusions: Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy-drinking individuals. Although the small sample requires confirmatory studies, these findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacologic target for treatment.

Trial registration: ClinicalTrials.gov NCT01190085.

Keywords: Alcoholism; craving; cue-reactivity; feeding peptides; ghrelin; neuroendocrinology.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Administration, Intravenous
  • Adult
  • Alcoholism / drug therapy*
  • Alcoholism / psychology*
  • Analysis of Variance
  • Blood Pressure / drug effects
  • Craving / drug effects*
  • Cues
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Ghrelin / administration & dosage*
  • Ghrelin / blood
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Saliva / metabolism
  • Statistics as Topic
  • Time Factors
  • Treatment Outcome

Substances

  • Ghrelin

Associated data

  • ClinicalTrials.gov/NCT01190085