Dataset Information

Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings.

ABSTRACT: Varenicline has been found to decrease alcohol-motivated behaviors. Recent warnings regarding aversive events associated with varenicline used in conjunction with alcohol warrant further investigation into the safety of the drug when combined with alcohol. The purpose of this preliminary investigation was to examine the effect of combining varenicline with a high, fixed dose of alcohol on subjective reactivity and cognitive function in adults with alcohol use disorders (AUDs).This double-blind, placebo-controlled preliminary investigation examined the effects of varenicline (0, 1, 2 mg/d) on subjective reactivity, cognition, perceptual motor function, and physiologic reactivity to a fixed dose of alcohol (vs. nonalcohol control beverage) using an established laboratory paradigm in smokers and nonsmokers meeting criteria for AUDs (n = 44). All participants had completed a parent varenicline study evaluating alcohol self-administration. Each subject completed 2 fixed-dose laboratory sessions assessing reactivity to a high-dose alcohol (0.08 g/dl) or a nonalcoholic control beverage, order counterbalanced.Varenicline attenuated alcohol-related increases in subjective intoxication and alcohol-related decreases in executive cognitive function. At baseline, varenicline reduced alcohol craving and diastolic blood pressure, and increased associative learning, working memory, and perceptual motor function. Varenicline produced nonspecific effects on diastolic blood pressure and heart rate. Overall, there were few differences in effects between 1 and 2 mg/d varenicline versus placebo.These preliminary results continue to support the safety and use of varenicline in combination with alcohol in individuals meeting criteria for AUDs.

SUBMITTER: Verplaetse TL

PROVIDER: S-EPMC4930423 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings.

Verplaetse Terril L TL Pittman Brian P BP Shi Julia M JM Tetrault Jeanette M JM Coppola Sabrina S McKee Sherry A SA

Alcoholism, clinical and experimental research 20160601 7

<h4>Background</h4>Varenicline has been found to decrease alcohol-motivated behaviors. Recent warnings regarding aversive events associated with varenicline used in conjunction with alcohol warrant further investigation into the safety of the drug when combined with alcohol. The purpose of this preliminary investigation was to examine the effect of combining varenicline with a high, fixed dose of alcohol on subjective reactivity and cognitive function in adults with alcohol use disorders (AUDs). ...[more]

PMID: 27246567

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Project description:Objective: Alcohol demand has been evaluated predominately as a trait-like construct, reflecting individual differences in alcohol's reinforcement value. Increases in state-dependent alcohol demand under intoxication have been demonstrated, indicating a potential mechanism that may influence drinking behavior. This study evaluated the roles of craving and subjective alcohol response (stimulation, sedation) in this process, testing whether increases in craving and stimulation, and reductions in sedation, predicted increased alcohol demand during a laboratory-based drinking episode. Method: Young adults (N = 90; 53% male; M age = 22.2) attended two sessions in a within-subjects alcohol/placebo design. Craving, stimulation, sedation, and alcohol demand (breakpoint, Omax, intensity) were assessed once before beverage consumption and at multiple points afterward at varying blood alcohol concentrations (M peak BrAC = 0.102 g%). Multilevel models tested associations between momentary and between-person predictors (craving, stimulation, sedation) and alcohol demand after accounting for sex, time trends, and baseline covariates. Results: When intoxicated, participants reported higher alcohol demand across the majority of the ascending limb and decreasing demand across the descending limb. Participants reported increased demand at moments when experiencing higher craving, ps ≤ .001, and stimulation, with momentary stimulation incrementally predicting demand above craving, ps ≤ .04. Between-persons, higher alcohol-induced craving was associated with increased demand, ps ≤ .001, whereas between-person stimulation and sedation were less robustly associated with demand indicators. Conclusions: Results indicate that within-person craving and stimulation during intoxication are independently associated with changes in alcohol's reinforcing value. Findings suggest the potential for state-dependent alcohol demand to serve as an additional motivational index of processes underlying ongoing drinking behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Project description:AimsThe orexigenic peptide ghrelin may enhance the incentive value of food-, drug- and alcohol-related rewards. Consistent with preclinical findings, human studies indicate a role of ghrelin in alcohol use disorders (AUD). In the present study an a priori hypothesis-driven analysis was conducted to investigate whether a Leu72Met missense polymorphism (rs696217) in the prepro-ghrelin gene (GHRL), is associated with AUD, alcohol consumption and subjective responses to alcohol.MethodAssociation analysis was performed using the National Institute on Alcohol Abuse and Alcoholism (NIAAA) clinical sample, comprising AUD individuals and controls (N = 1127). Then, a post-hoc analysis using data from a human laboratory study of intravenous alcohol self-administration (IV-ASA, N = 144) was performed to investigate the association of this SNP with subjective responses following a fixed dose of alcohol (priming phase) and alcohol self-administration (ad libitum phase).ResultsThe case-control study revealed a trend association (N = 1127, OR = 0.665, CI = 0.44-1.01, P = 0.056) between AUD diagnosis and Leu72Met. In AUD subjects, the SNP was associated with significantly lower average drinks per day (n = 567, β = -2.49, 95% CI = -4.34 to -0.64, P = 0.008) and significantly fewer heavy drinking days (n = 567, β = -12.00, 95% CI = -19.10 to -4.89, P < 0.001). The IV-ASA study further revealed that 72Met carriers had greater subjective responses to alcohol (P < 0.05) when compared to Leu72Leu both at priming and during ad lib self-administration.ConclusionAlthough preliminary, these findings suggest that the Leu72Leu genotype may lead to increased risk of AUD possibly via mechanisms involving a lower response to alcohol resulting in excessive alcohol consumption. Further investigations are warranted.Short summaryWe investigated whether a Leu72Met missense polymorphism in the prepro-ghrelin gene, is associated with alcohol use disorder, alcohol consumption and subjective responses to alcohol. Although preliminary, results suggest that the Leu72Leu genotype may lead to increased risk of alcohol use disorder possibly via mechanisms involving a lower response to alcohol.

Project description:BackgroundSelf-reported consumption is pervasive in alcohol research, though retrospective recall bias is a concern. Fine-grained methods are designed to limit retrospection; yet, discrepancies can arise when comparing responses on fine-grained surveys with responses to retrospective surveys across weeks or months. Many fine-grained studies use both repeated daily surveys (RDS) and end-of-day (EOD) summaries, but little research has examined whether these survey types are consistent. The purpose of this study was to quantify the magnitude and directionality of discrepancy between EOD summaries and RDS and identify alcohol-related predictors of discrepancy.MethodsAs a part of a larger study, college student alcohol and cannabis users (N = 341; 53% women; Mage = 19.79 years) were recruited to complete 56 days of data collection, including 5 daily assessments of their substance use and related constructs, one of which included an EOD summary of the previous day. Generalized linear mixed-effects models were used to examine between- and within-person predictors of a 5-category, discrepancy outcome: no discrepancy, low discrepancy where RDS < EOD, low discrepancy where EOD < RDS, high discrepancy where RDS < EOD, and high discrepancy where EOD < RDS.ResultsDiscrepancies between EOD and RDS were observed in both directions. Alcohol problems predicted more alcohol consumption reported on the EOD survey than across RDS. Within-person alcohol quantity and hourly rate of consumption were most strongly related to less alcohol consumption reported on the EOD survey. Between- and within-person peak subjective intoxication and within-person liquor consumption were associated with discrepancies in both directions.ConclusionsSurveys requiring more retrospection may overestimate alcohol consumption in problematic drinkers and underestimate consumption on days where more alcohol is consumed than typical. Evidence also suggests that greater day-to-day instability in alcohol behavior is linked to less consistent reporting overall. More research is needed to discern factors contributing to inconsistent reporting on fine-grained surveys to maximize the validity of reports.

Dataset Information

Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings.

Publications

Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings.

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