Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers.

Xiaosi Gu,Terry Lohrenz,Ramiro Salas,Ulrich Kirk,Philip R Baldwin,Alireza Soltani,P Read Montague,Paul M Cinciripini

doi:10.3389/fpsyt.2016.00126

Abstract

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 nicotine-addicted 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.

Highlights

Craving is a core symptom of drug addiction [1,2,3] and has been proven to be much more difficult to treat than physical dependency symptoms [4]
There was no main effect of belief or nicotine on learning behavior
Smokers reported a significant reduction in craving when they smoked a nicotine cigarette and were told “nicotine” [one-sample t(23) = −3.02, P < 0.01]; such decrease in craving was absent in the case of being told “no nicotine” and smoked a nicotine cigarette (P > 0.1)

Summary

Introduction

Craving is a core symptom of drug addiction [1,2,3] and has been proven to be much more difficult to treat than physical dependency symptoms [4]. We found that in non-deprived smokers, belief about nicotine’s presence modulated both neural learning signals in the ventral striatum as well as learning behavior when participants smoked a cigarette with nicotine [15]. These results demonstrate that belief has a powerful effect in overriding the effects of nicotine on reward learning. It remained unclear, whether such belief–drug interactions could modulate other aspects of drug addiction such as craving. The current study uses a balanced placebo design to directly examine the impact of belief about drugs (i.e., nicotine) on subjective craving and associated patterns of neural activation measured by fMRI among deprived smokers

Methods

Results

Conclusion