Evidence map›Paper›PMID 23506999›Full record

Trial reportBiological psychiatry2013

Down-regulation of amygdala and insula functional circuits by varenicline and nicotine in abstinent cigarette smokers.

Matthew T Sutherland, Allison J Carroll, Betty Jo Salmeron, Thomas J Ross, L Elliot Hong, Elliot A Stein

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 2 pooled it
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020
    Trial
  5. Trial
  6. Trial
  7. Pharmacological intervention and abstinence in smokers undergoing cessation treatment: A psychophysiological study.International journal of psychophysiology : official journal of the International Organization of Psychophysiology · 2018
    Trial
  8. Trial
  9. Trial
  10. Trial
  11. Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers.The international journal of neuropsychopharmacology · 2015
    Trial
  12. Article
  13. A widespread internal brain state for fentanyl withdrawal.bioRxiv : the preprint server for biology · 2026
    Article
  14. Article
  15. Brain reactivity to nicotine cues mediates the link between resting-state connectivity and cue-induced craving in individuals who smoke or vape nicotine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article

23 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Matthew T SutherlandDepartment of Psychology, Florida International University, Miami, Florida. Electronic address: masuther@fiu.edu.
Allison J Carroll
Betty Jo Salmeron
Thomas J Ross
L Elliot Hong
Elliot A Stein
National Institute on Drug Abuse · USNational Institutes of Health · USFlorida International University · USUniversity of Maryland, Baltimore · US

Funding

Functional and Structural Brain Circuits Underlying SmokingZIADA000573 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI STEIN, ELLIOT A · 2010 to 2021
$19.4M
Shared Neural Circuitry in Comorbid Schizophrenia and Nicotine AddictionR01DA027680 · NIDA · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT · 2010 to 2014
$2.4M
Intramural NIH HHS Z99 DA999999NIDA NIH HHS R01 DA027680
6 · The paper itself

Abstract

backgroundAlthough the amygdala and insula are regarded as critical neural substrates perpetuating cigarette smoking, little is known about their circuit-level interactions with interconnected regions during nicotine withdrawal or following pharmacotherapy administration. To elucidate neurocircuitry associated with early smoking abstinence, we examined the impact of varenicline and nicotine, two modestly efficacious pharmacologic cessation aids, on amygdala- and insula-centered circuits using resting-state functional connectivity (rsFC).

methodsIn a functional magnetic resonance imaging study employing a two-drug, placebo-controlled design, 24 overnight-abstinent smokers and 20 nonsmokers underwent ∼17 days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. We examined the impact of varenicline and nicotine (both alone and in combination) on amygdala- and insula-centered rsFC using seed-based assessments.

resultsBeginning with a functionally defined amygdala seed, we observed that rsFC strength in an amygdala-insula circuit was down-regulated by varenicline and nicotine in abstinent smokers. Using this identified insula region as a new seed, both drugs similarly decreased rsFC between the insula and constituents of the canonical default-mode network (posterior cingulate cortex, ventromedial/dorsomedial prefrontal cortex, parahippocampus). Drug-induced rsFC modulations were critically linked with nicotine withdrawal, as similar effects were not detected in nonsmokers.

conclusionsThese results suggest that nicotine withdrawal is associated with elevated amygdala-insula and insula-default-mode network interactions. As these potentiated interactions were down-regulated by two pharmacotherapies, this effect may be a characteristic shared by pharmacologic agents promoting smoking cessation. Decreased rsFC in these circuits may contribute to amelioration of subjective withdrawal symptoms.

Indexed as

Smoking CessationAdolescentAdultAmygdalaBenzazepinesBrain MappingCerebral CortexDouble-Blind MethodDown-RegulationFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNicotineNicotinic AgonistsBenzazepinesNicotineNicotinic AgonistsQuinoxalinesVareniclineAmygdalainsulanicotineresting-state functional connectivityvareniclinewithdrawal

Identifiers

PMID23506999
PMCPMC3775982
OpenAlexW2066823901

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.