Effects of naltrexone on alcohol self-administration and craving: meta-analysis of human laboratory studies.
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ABSTRACT:
SUBMITTER: Hendershot CS
PROVIDER: S-EPMC6139429 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
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Effects of naltrexone on alcohol self-administration and craving: meta-analysis of human laboratory studies.
Hendershot Christian S CS Wardell Jeffrey D JD Samokhvalov Andriy V AV Rehm Jürgen J
Addiction biology 20160714 6
Randomized clinical trials have established the efficacy of naltrexone for reducing quantity of alcohol consumption and incidence of relapse to heavy drinking. To evaluate putative treatment mechanisms, human laboratory studies have examined naltrexone's effects on alcohol responses and self-administration during short-term medication protocols. Results from these studies are inconsistent and have yet to be examined in aggregate. This meta-analysis aimed to quantify naltrexone's effects on alcoh ...[more]
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Project description:BACKGROUND:Despite a rich literature on human laboratory paradigms of subjective response (SR) to alcohol, craving for alcohol, and alcohol self-administration, few studies have examined the interplay across these 3 constructs. The present study addresses this gap in the literature by examining the interplay between SR, craving, and self-administration in the human laboratory. METHODS:Data were culled from a medication study (NCT02026011) in which heavy drinking participants of East Asian ancestry completed 2 double-blinded and counterbalanced experimental sessions. In each experimental session, participants received a priming dose of intravenous (IV) alcohol to a target breath alcohol concentration (BrAC) of 0.06 g/dl and measures of SR (stimulation and sedation) and alcohol craving were collected across rising BrACs. The IV alcohol challenge was immediately followed by a 1-hour alcohol self-administration period. RESULTS:Mixed model analyses found a positive and significant relationship between the slope of stimulation and the slope of craving during the alcohol challenge. The relationship between sedation and craving, however, was not significant. The slope of craving during the alcohol challenge significantly predicted a higher number of mini-drinks consumed and lower latency to first drink. Further, mediation analyses found that craving was a significant mediator of the relationship between stimulation and total number of mini-drinks consumed, but the same pattern was not found for sedation. CONCLUSIONS:Insofar as alcohol self-administration represents the end point of interest for a host of experimental and clinical research questions, the present study suggests that alcohol craving represents a more proximal predictor of self-administration than measures of alcohol-induced stimulation. It is recommended that human laboratory models interpret measures of SR and craving in light of their relative predictive utility for drinking outcomes.
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Project description: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.
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Project description:Motivational models of alcohol use suggest that individual differences in sensitivity to the acute subjective effects of alcohol play an important role in motivational pathways to alcohol use. However, few studies have examined the link between drinking motives and subjective responses to alcohol. This study investigated the associations of coping and enhancement drinking motives with subjective stimulant and sedative effects during a laboratory alcohol administration session. We also examined whether stimulation and sedation following alcohol administration mediated the relationships between drinking motives and postalcohol ratings of alcohol wanting and liking.Heavy episodic drinkers (n = 147, ages 19 to 25) at 2 sites participated in an intravenous alcohol administration session in which blood alcohol concentration was raised to a target of 80 mg% over 20 minutes. Participants completed measures of stimulation and sedation at baseline and 20 minutes and also rated alcohol liking and wanting at 20 minutes. Drinking motives and alcohol use were assessed during a previous laboratory visit.A path analysis controlling for baseline stimulation and sedation showed that enhancement motives were positively associated with postalcohol stimulation and negatively associated with postalcohol sedation. In contrast, coping motives were positively associated with postalcohol sedation. In turn, postalcohol stimulation, but not sedation, was associated with alcohol wanting and liking. Further, indirect pathways from enhancement motives to postalcohol wanting and liking mediated through postalcohol stimulation were statistically significant. Coping motives, on the other hand, were directly associated with increased postalcohol wanting and liking.The results demonstrate that drinking motives are linked with individual differences in sensitivity to the effects of alcohol, which may serve as a mechanism underlying alcohol reinforcement and the motivation to consume more alcohol during a drinking episode.
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