Varenicline effects on craving, cue reactivity, and smoking reward

Abstract

Rationale Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist that has been found to be effective for treating tobacco dependence. However, the subjective and behavioral mediators of its efficacy are not known. Objectives Using multiple sessions of laboratory-based assessment, this double-blind, placebo-controlled experiment was designed to test if varenicline reduced both tonic and cue-provoked tobacco cravings, and if it attenuated perceived reward from smoking. Methods Participants in the present analysis include 100 smokers who were scheduled for three assessment sessions: at baseline, before receiving medication; at mid-run-in, 5– 7 days after beginning medication; and after full dosage was reached, 12–15 days. Following overnight abstinence, each session included assessment of tonic craving, reactivity (including craving) to smoking cues, expected value of a cigarette, smoking behavior, and self-reported reward following smoking. Results Varenicline, compared to placebo, reduced tonic craving, cue-provoked craving by the final assessment, the expected value of cigarettes, number of puffs and time spent smoking, and self-reported reward (i.e., satisfaction) from smoking. Conclusions Results showing that varenicline reduced tonic craving levels and perceived reward from smoking are consistent with reports from clinical trials, strengthening the evidence in support of these subjective mechanisms of action. This is the first placebo-controlled study to demonstrate that varenicline reduced cue-provoked cravings, thereby offering another potential mediator of its therapeutic effects. Findings may aid in the development of more targeted interventions for tobacco dependence.

Reward Anticipation Is Differentially Modulated by Varenicline and Nicotine in Smokers

“…This informs the underlying neurobiological mechanisms of VAR's efficacy in smoking reduction. The observed downregulation of ACC is directionally consistent with VAR-mediated reductions in smoking-cue-related medial OFC activation in smokers (Franklin et al, 2011), as well as behavioral and subjective reports of reductions in nicotine craving in smokers administered VAR (Brandon et al, 2011;Patterson et al, 2009).…”

“…Thus, we speculate that the differential effects of VAR across levels of gain magnitude may protect treatmentseeking smokers from nicotine withdrawal-precipitated relapse. Indeed, VAR downregulates the salience of smoking-related cues in both current (Brandon et al, 2011) and abstinent (Patterson et al, 2009) smokers.…”

“…VAR has been broadly implicated in the reduction of reward signaling, selectively decreasing voluntary alcohol intake in both rodents (Hendrickson et al, 2010;Steensland et al, 2007) and humans (Fucito et al, 2011;McKee et al, 2009). Administration of VAR decreases subjective reports of nicotine craving (Brandon et al, 2011;Patterson et al, 2009) and smoking cue-induced activity in the medial OFC (Franklin et al, 2011) in nontreatmentseeking smokers. In addition, VAR reduces subjective reward of nicotine during lapses in smoking cessation (Oncken et al, 2006;Patterson et al, 2009).…”

Pharmacokinetic-Pharmacodynamic Modeling of the Effect of Varenicline on Nicotine Craving in Adult Smokers

“…[8][9][10] Similar findings have been reported from laboratory investigations with varenicline when self-reporting smoking reward was assessed immediately after smoking. [11][12][13] The present report is part of a study, evaluating the effect of varenicline on ameliorating abstinence-and cue-induced nicotine craving and withdrawal symptoms in a population of 40 smokers not currently intending to quit. 14 The cue-reactivity model was based on a rigorous laboratory-based assessment paradigm including in vivo exposure to smoking cues, specifically designed to provoke craving and assess the effects of smoking cues on the urge to smoke and withdrawal symptoms.…”

Le craving comme symptôme central de la toxicomanie : de ses fondements neurobiologiques à sa pertinence clinique

“…La varénicline, un agoniste partiel des récepteurs nicotiniques alpha4-beta2, a démontré une réduction du craving tonique et phasique comparé au placebo dans une étude de 100 fumeurs (Brandon et al, 2011). Ce mécanisme contribuerait à l'efficacité de ce médicament pour l'arrêt tabagique.…”