Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals

Abstract

Rationale The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas. Objectives This pilot study tested varenicline’s effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals. Methods Thirty-five such individuals (mean age = 30, 57% male, 76% heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC). Results Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas. Conclusions These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.

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

“…Individuals who feel less intoxicated may decide to continue drinking or underestimate the effects of alcohol on cognitive ability and decision-making, potentially leading to increased alcohol-related consequences (e.g., driving under the influence, legal risk). However, findings from the parent study and prior established findings demonstrate that varenicline is associated with reduced alcohol consumption (McKee et al, 2009, Fucito et al, 2011, Mitchell et al, 2012, Litten et al, 2013, Verplaetse et al, in press ), reduced alcohol craving (Schacht et al, 2014), potentiated subjective aversive effects of alcohol (Childs et al, 2012), and reduced cue-elicited brain activation in the medial orbitofrontal cortex (OFC)(Schacht et al, 2014). Alternatively, individuals who experience less alcohol-related cognitive impairment may be less likely to make poor or risky decisions while intoxicated.…”

Varenicline Reduces Context-Induced Relapse to Alcohol-Seeking through Actions in the Nucleus Accumbens

“…In humans, varenicline reduced alcohol craving and cue-elicited activation of the orbitofrontal cortex, with no effect on drinking behavior (Schacht et al, 2014). Varenicline dose-dependently attenuated cue-induced reinstatement of alcohol-seeking in rats (Funk et al, 2016;Wouda et al, 2011), congruent with doserelated reductions in cue-induced cocaine- (Guillem and Peoples, 2010) and nicotine-seeking (Le Foll et al, 2011, but see Wouda et al, 2011, andO'Connor et al, 2009).…”

The Corticotropin Releasing Factor Receptor 1 in Alcohol Use Disorder: Still a Valid Drug Target?

“…Varenicline was never tested for effects on stress-induced reinstatement, but it inhibited cue-induced reinstatement of alcohol seeking in Wistar rats (Wouda et al, 2011, Funk et al, 2016) and cue-induced alcohol seeking in baboons (Kaminski and Weerts, 2014). It has also reduced alcohol self-administration in animals (Steensland et al, 2007, Bito-Onon et al, 2011, Wouda et al, 2011, Hendrickson et al, 2010, Kaminski and Weerts, 2014, Sotomayor-Zárate et al, 2013), and decreased drinking and alcohol craving in human smokers and non-smokers (McKee et al, 2009, Fucito et al, 2011, Mitchell et al., 2012, Plebani et al, 2013, Schacht et al, 2014, Roberts et al, 2017, Litten et al, 2013). …”