Intravenous ghrelin administration increases alcohol craving in alcohol-dependent heavy drinkers: a preliminary investigation.
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.
Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland; Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence. Electronic address: lorenzo.leggio@nih.gov.
Lorenzo
L
Leggio
Decision Sciences Institute, Pacific Institute for Research and Evaluation, Pawtucket; Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island.
William H
WH
Zywiak
Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence.
Samuel R
SR
Fricchione
Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska.
Steven M
SM
Edwards
Departments of Pathology, Neurology, and Neurosurgery, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, Rhode Island.
Suzanne M
SM
de la Monte
Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island; Veterans Affairs Medical Center, Providence, Rhode Island.
Robert M
RM
Swift
Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island.
George A
GA
Kenna
D061605:Administration, Intravenous; D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology*; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D066249:Craving / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage* / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism; D013223:Statistics as Topic; D013997:Time Factors; D016896:Treatment Outcome
D054439:Ghrelin
Alcoholism; craving; cue-reactivity; feeding peptides; ghrelin; neuroendocrinology