Dataset Information

Effects of varenicline on cognitive performance in heavy drinkers: Dose-response effects and associations with drinking outcomes.

ABSTRACT: Varenicline reduces drinking in people with alcohol use disorder, but little is known about the mechanisms underlying this effect. Varenicline targets ?4?2 and ?7 nicotinic acetylcholine receptors, which are associated with several cognitive functions such as working memory. Varenicline may improve drinking outcomes by enhancing cognitive functioning. The current manuscript reports on cognitive outcomes from a placebo-controlled, double-blind human laboratory experiment examining the effects of varenicline on drinking behavior (Verplaetse et al., 2016a). Participants were 55 adult heavy drinkers who met criteria for an alcohol use disorder. They were randomized to receive varenicline (1 mg/day, 2 mg/day) or placebo. They completed a baseline assessment of cognitive functioning (i.e., digits backward task, continuous performance task) before starting medication. After a medication titration period, they attended a laboratory session (post medication Day 8) where they completed the cognitive assessment battery and an alcohol-primed ad libitum drinking task. Blood was collected to measure plasma varenicline levels. Varenicline produced dose-dependent improvements in working memory. Although there was no significant effect of oral varenicline dose on response time on the continuous performance task, participants with higher levels of plasma varenicline showed greater improvement of reaction time (RT). Among participants receiving 2 mg/day varenicline, larger improvements in working memory were associated less drinking, although mediation analyses did not find a significant indirect effect. These findings suggest that varenicline can improve working memory above baseline levels in heavy drinkers. Varenicline may reduce rates of alcohol use by improving working memory. (PsycINFO Database Record

SUBMITTER: Roberts W

PROVIDER: S-EPMC5797996 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Preclinical and emerging clinical evidence indicates that varenicline, a nicotinic partial agonist approved for smoking cessation, attenuates alcohol seeking and consumption. Reductions of alcohol craving have been observed under varenicline treatment and suggest effects of the medication on alcohol reward processing, but this hypothesis remains untested. METHODS:In this double-blind, placebo-controlled randomized experimental medicine study, 29 heavy drinkers underwent a functional magnetic resonance imaging scan after 2 weeks of varenicline (2mg/d) or placebo administration. During functional magnetic resonance imaging, participants performed the Alcohol-Food Incentive Delay task, where they could earn points for snacks or alcohol. At baseline and after 3 weeks of medication, participants underwent intravenous alcohol self-administration sessions in the laboratory. RESULTS:During the functional magnetic resonance imaging scan, participants in the varenicline group (N=17) reported lower feelings of happiness and excitement on subjective mood scales when anticipating alcohol reward compared with the placebo group (N=12). Linear mixed effects analysis revealed that anticipation of alcohol reward was associated with significant blood oxygen level dependent activation of the ventral striatum, amygdala, and posterior insula in the placebo group; this activation was attenuated in the varenicline group. The varenicline group showed no difference in intravenous alcohol self-administration relative to the placebo group for either session. Participants with higher insula activation when anticipating alcohol reward showed higher alcohol self-administration behavior across groups. CONCLUSIONS:Our findings suggest that varenicline decreases blood oxygen level dependent activation in striato-cortico-limbic regions associated with motivation and incentive salience of alcohol in heavy drinkers. This mechanism may underlie the clinical effectiveness of varenicline in reducing alcohol intake and indicates its potential utility as a pharmacotherapy for alcohol use disorders.

Project description:BACKGROUND:Pharmacotherapies for alcohol use disorder have been shown to reduce hazardous drinking and improve overall health. The effect sizes for the effectiveness of these medications, however, are small, underscoring the need to expand the range of therapeutics and develop personalized treatment approaches. Recent studies have suggested that varenicline, an ?4?2-nicotinic partial agonist widely used for smoking cessation, can help alcoholics reduce drinking, but the neurocognitive underpinnings of its effectiveness remain largely unexplored. METHODS:In this double-blind study, 32 heavy drinkers were randomized to receive varenicline (2 mg/d) or placebo. After 2 weeks of dosing, participants underwent functional MRI scans, during which they viewed images of faces with either neutral or fearful expressions at baseline and following an intravenous alcohol infusion to a target breath alcohol concentration of 80 mg%. Blood oxygen level-dependent (BOLD) response was analyzed with Analysis of Functional Neuroimaging software. Linear mixed-effects models were used to examine the effects of facial expression (fearful vs. neutral) and medication (placebo vs. varenicline) on BOLD response. The effect of medication on measures of subjective response to alcohol was also examined. RESULTS:Results indicated a significant facial expression-by-medication interaction in the left amygdala. The groups showed equivalent activation to neutral faces, but, whereas the placebo group showed increased activation to fearful faces, the varenicline group showed no change in activation. Amygdala activation to fearful faces correlated with number of drinks in the previous 90 days and Obsessive Compulsive Drinking Scale scores. There was no effect of varenicline on subjective response to alcohol. CONCLUSIONS:Our results indicate that varenicline may disrupt amygdala response to fearful faces in heavy drinkers. Further, amygdala activation correlated with alcohol consumption, suggesting that the effects of varenicline may be related to aspects of drinking behavior. These results suggest that amygdala response to fearful faces may be developed as a biomarker of the effectiveness of medications being developed for the treatment of alcohol use disorder.

Dataset Information

Effects of varenicline on cognitive performance in heavy drinkers: Dose-response effects and associations with drinking outcomes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets