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Intravenous Ghrelin Administration Increases Alcohol Craving in Alcohol-Dependent Heavy Drinkers: A Preliminary Investigation

  • Lorenzo Leggio
    Correspondence
    Address correspondence to Lorenzo Leggio, M.D., Ph.D., M.Sc., National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, 10 Center Drive (10CRC/15330), MSC 1108; Room 1-5429, Bethesda, MD 20892-1108
    Affiliations
    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
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  • William H. Zywiak
    Affiliations
    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
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  • Samuel R. Fricchione
    Affiliations
    Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence
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  • Steven M. Edwards
    Affiliations
    Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska
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  • Suzanne M. de la Monte
    Affiliations
    Departments of Pathology, Neurology, and Neurosurgery, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, Rhode Island
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  • Robert M. Swift
    Affiliations
    Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island

    Veterans Affairs Medical Center, Providence, Rhode Island
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  • George A. Kenna
    Affiliations
    Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island
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      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.

      Key Words

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      Linked Article

      • Ghrelin in Addictive Behaviors: Plenus Venter Non Studet Libenter
        Biological PsychiatryVol. 76Issue 9
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          The medieval proverb that a full stomach does not like to “study” (“studere” in its original sense—directing one’s efforts or attention to something, or striving after it) may be useful in understanding the work of Leggio et al. published in this issue of Biological Psychiatry (1). It is a fundamental human experience that one’s motivation to pursue—or strive for—stimulation is attenuated during a state of satiety. Dullness, laggardness, and phlegm are associated with a full belly. So what does that mean for addiction research?
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