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

Abstract

Background There is a need to identify novel pharmacological targets to treat alcoholism. Animal and human studies suggest a role of 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. Non-treatment seeking alcohol-dependent heavy drinking individuals were randomized to receive intravenous ghrelin 1mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cuereactivity 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 ANCOVA 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 vs. 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: n.s.). No significant differences in side effects were found (p: n.s.). 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 pharmacological target for treatment.

Peptide YY and ghrelin predict craving and risk for relapse in abstinent smokers

“…A review of this work is beyond the scope of this paper, but the reader may find the following original works and reviews helpful (Dickson et al, 2011; Landgren et al, 2011; Suchankova et al, 2013). Further understanding of the relationship between appetite hormones and craving for nicotine could be greatly enhanced by replicating the recent study of intravenous exogenous ghrelin administration on alcohol cue-induced craving in heavy drinkers (Leggio et al, in press). Extending this to PYY is also feasible as intravenous PYY has been used safely in human obesity research for over a decade (Zac-Varghese, De Silva, & Bloom, 2011).…”

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

“…More specifically, gut-brain peptides, which have been traditionally known to regulate food intake and energy balance (Ahima & Antwi 2008), seem to play a pivotal role in mediating the reinforcing properties of alcohol and other drugs of abuse Abizaid et al 2011;Clifford et al 2012;Egecioglu, Engel, & Jerlhag 2013a;Suchankova et al 2013a;Engel & Jerlhag 2014;Vadnie et al 2014;Vallof et al 2016c). Notably, ghrelin, glucagon-like peptide-1 and neuromedin U have been shown to alter alcohol-induced reward phenotypes by acting on the mesolimbic dopamine system (Kraus et al 2005;Leggio et al 2011;Jerlhag et al 2011b;Landgren et al 2012;Suchankova et al 2013b;Leggio et al 2014;Vallof et al 2016a;Vallof et al 2016b). Other hormones, for example, amylin, have been recently studied for their role to control energy balance through gut-brain axis regulation (Reda, Geliebter, & Pi-Sunyer 2002;Lutz 2009).…”

The Effects of Ghrelin Antagonists [D‐Lys3]‐GHRP‐6 or JMV2959 on Ethanol, Water, and Food Intake in C57BL/6J Mice

“…Alcohol dependence dysregulates the ghrelin system and a positive correlation has been found between ghrelin levels and craving in actively drinking patients diagnosed with alcohol dependence (Addolorato et al, 2006; Leggio et al, 2012). This correlation has been further tested to show that intravenous ghrelin administration causes an increased craving score on the Alcohol Visual Analog Scale in alcoholics (Leggio et al, 2014). Abstinence from alcohol increases ghrelin levels and these levels are directly correlated with the amount of time abstinent (Kraus et al, 2005; Kim et al, 2005).…”