Little is known about the specific neural mechanisms through which cognitive factors
influence craving and associated brain responses, despite the initial success of cognitive
therapies in treating drug addiction. In this study, we investigated how cognitive
factors such as beliefs influence subjective craving and neural activities in nicotineaddicted
individuals using model-based functional magnetic resonance imaging (fMRI)
and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced
placebo design, which crossed beliefs about nicotine (told “nicotine” vs. told “no
nicotine”) with the nicotine content in a cigarette (nicotine vs. placebo) which participants
smoked immediately before performing a fMRI task involving reward learning. Subjects’
reported craving was measured both before smoking and after the fMRI session. We
found that first, in the presence of nicotine, smokers demonstrated significantly reduced
craving after smoking when told “nicotine in cigarette” but showed no change in craving
when told “no nicotine.” Second, neural activity in the insular cortex related to craving
was only significant when smokers were told “nicotine” but not when told “no nicotine.”
Both effects were absent in the placebo condition. Third, insula activation related to
computational learning signals was modulated by belief about nicotine regardless of nicotine’s
presence. These results suggest that belief about nicotine has a strong impact on
subjective craving and insula responses related to both craving and learning in deprived
smokers, providing insights into the complex nature of belief–drug interactions.
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