Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokers

Abstract

Rationale The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome. Objectives This study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design. Methods Following overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2 mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-minute intervals. At 4-hours post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil. Results At 4-hours post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results. Conclusions Acute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy.

Individual variables related to craving reduction in cue exposure treatment

“…5 Individual variables related Hitsman et al, 2013;Shiffman & Ferguson, 2008), very few studies have explored which variables are associated with craving reductions. Those studies have mainly explored the influence of gender (Collins, Nair, & Komaroff, 2011;Unrod et al, 2013), nicotine dependence (Canterberry et al, 2013;Kober et al, 2010;Li et al, 2013) and…”

Functional network connectivity predicts treatment outcome during treatment of nicotine use disorder

“…Varenicline is an established treatment for NUD (Hartmann-Boyce et al, 2014), and its efficacy is likely mediated, in part, by reductions in craving (Ashare et al, 2012; Hajek et al, 2011; Hitsman et al, 2013), although this has not been observed in all studies of varenicline (Jhanjee et al, 2015). Investigations into the effects of varenicline on withdrawal have been even more mixed with some showing improvements in withdrawal (Hitsman et al, 2013) and others not (Brandon et al, 2011; Jhanjee et al, 2015).…”

“…Investigations into the effects of varenicline on withdrawal have been even more mixed with some showing improvements in withdrawal (Hitsman et al, 2013) and others not (Brandon et al, 2011; Jhanjee et al, 2015). Finally, there is some evidence to suggest that varenicline may be acting via improvements in inhibitory control and attention (and thus impulsiveness) as well (Austin et al, 2014; Rhodes et al, 2012).…”

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

“…[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. Results showed that a single dose of varenicline reduced tonic craving levels in smokers who refrained from smoking, but not cue-provoked craving.…”