Neural Basis of Smoking-Induced Relief of Craving and Negative Affect: Contribution of Nicotine

Paul Faulkner, Dara G Ghahremani, Rachel F Tyndale, Neil Paterson, Chelsea M Cox, Nathaniel Ginder, Gerhard S Hellemann, Edythe D London

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Smoking-induced relief of craving and withdrawal promotes continued
cigarette use. Understanding how relief is produced, and the role of
nicotine in this process, may facilitate development of new smokingcessation
therapies. As the US Food and Drug Administration considers
setting a standard for reduced nicotine content in cigarettes to improve
public health, knowledge of how nicotine contributes to relief also can
inform policy. We assessed effects of nicotine using resting state functional
MRI and behavioral assessments of craving and negative affect. Twentyone
young (18-25 years old) daily smokers underwent overnight
abstinence on 4 days. On each of the following mornings, they self-rated
their cigarette craving and negative affect, and underwent resting-state
fMRI before and after smoking a cigarette that delivered 0.027, 0.110,
0.231, or 0.763 mg nicotine. Functional connectivity between the anterior
insula and anterior cingulate cortex (ACC), and between the nucleus
accumbens and orbitofrontal cortex (OFC), was assessed. Smoking reduced
craving, negative affect and nucleus accumbens-OFC connectivity
irrespective of nicotine dose, with positive correlations of the effects on
behavioral and connectivity measures. Only the highest nicotine dose
(0.763 mg) reduced right anterior insula-ACC connectivity; this reduction
was positively correlated with the behavioral effects of the 0.763-mg dose
only. While nicotine-based therapies may act on right anterior insula-ACC
functional circuits to facilitate smoking cessation, non-nicotine (e.g., the
conditioned, sensorimotor) aspects of smoking may promote cessation by
reducing OFC-accumbens connectivity to alleviate withdrawal.

© 2018, Society for the Study of Addiction. The attached document (embargoed until 11/10/2019) is an author produced version of a paper published in ADDICTION BIOLOGY uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link below. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.
Original languageEnglish
JournalAddiction Biology
Early online date11 Oct 2018
Publication statusPublished - 13 Aug 2019


  • nicotine
  • insula
  • striatum

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