Brain Responses to Cigarette-Related and Emotional Images in Smokers During Smoking Cessation: No Effect of Varenicline or Bupropion on the Late Positive Potential

Abstract

Introduction: Varenicline and bupropion are two effective smoking cessation pharmacotherapies. Researchers have hypothesized that they might be effective, in part, because they reduce cue reactivity and cue-induced cravings. Here, we used event-related potentials (ERPs) to directly measure brain responses to cigarette-related and other motivationally relevant images during a pharmacologically aided quit attempt.

Methods: Smokers involved in a 12-week placebo-controlled double-blind clinical trial of smoking cessation medications (varenicline, bupropion, placebo) took part in the study. We assessed participants at two time points: 24 h (n = 140) and 4 weeks (n = 176) after the quit date. At both sessions, we measured the amplitude of the late positive potential (LPP), an ERP component reliably associated with motivational relevance, and self-reported tonic craving using the brief version of the Questionnaire of Smoking Urges (QSU-Brief).

Results: At both sessions, emotional and cigarette-related images evoked significantly larger LPPs than neutral images. Neither drug type nor smoking abstinence altered this effect at either session. At both sessions, varenicline and bupropion significantly reduced self-reported tonic craving relative to the placebo condition.

Conclusions: While both varenicline and bupropion reduced self-reported tonic craving, neither medication altered the amplitude of the LPP to cigarette-related or emotional pictures in smokers attempting to quit. These medications may influence abstinence by means other than by reducing neuroaffective responses to cigarette-related cues. Smokers should be prepared for the likelihood that even after several weeks of successful abstinence, once treatment ends, cigarette-related cues may remain motivationally relevant and trigger cravings that might lead to relapse.

Implications: Bupropion and varenicline do not alter electrophysiological responses, as measured by the LPP, to cigarette-related and emotional images. These findings help explain why cigarette-related cues can trigger relapse when smoking cessation medication treatments end.

Figure 1.

(A) Waveforms for each picture category at 24-h post-quit. The box highlights the time region of interest (ROI) used to compute the late positive potential (LPP) across the electrodes highlighted in the inset. The amplitude of the LPP evoked by neutral images was significantly lower than the LPP evoked by pleasant, unpleasant, and cigarette-related images (see bar graph). (B) Waveforms for each picture category at 4 weeks post-quit. The box highlights the time region of interest (ROI) used to compute the late positive potential (LPP) across the electrodes highlighted in the inset. The amplitude of the LPP evoked by neutral images was significantly lower than the LPP evoked by pleasant, unpleasant, and cigarette-related images (see bar graph). Note: CIG = cigarettes, PLE = pleasant, UNP = unpleasant, NEU = neutral. The error bars represent the 95% confidence intervals.