Effects of varenicline and cognitive bias modification on neural response to smoking-related cues: a randomised control trial

Abstract

Drug-related cognitive biases have been positively associated with drug-craving and increased likelihood of relapse. Cognitive bias modification paradigms have been developed to attenuate cognitive biases but there have been few studies that examined neural responses to these paradigms. This study compared neural responses following CBM and explored whether CBM effects were potentiated by varenicline administration. This was a double-blind placebo-controlled study with two between subject factors of drug (varenicline, placebo) and CBM (attend towards smoking cues, train away from smoking cues, control training) that recruited daily (≥ 10 cigarettes per day) non-treatment seeking smokers. Participants (n = 67, 53% female) were randomised to one-week of drug administration (varenicline or placebo) before attending a study session at which they were randomised to CBM condition, and underwent an fMRI scan were they were presented with smoking and neutral cues. Neural response to smoking (vs. neutral) cues, cognitive bias, craving and mood were assessed. There was no evidence of CBM effects on any outcomes. There was evidence of effects of varenicline on craving, with greater reductions in craving in the week preceding the study session in the varencline group (p = 0.04, η_p² = .06). There was also evidence of a drug by CBM interaction for neural responses (z = 3.78, p <0.001). Compared to placebo, varenicline was associated with greater activation in the right temporal middle gyrus in the CBM control condition, compared to an opposite effect in the CBM “attend towards” condition. These data suggest that CBM does not modify cognitive bias, subjective craving and mood, or neural response to smoking cues. There was also no evidence that CBM effects were potentiated by varenicline.