Evidence map›Paper›PMID 26355604›Full record

ArticlePloS one2015

Effects of Menthol on Nicotine Pharmacokinetic, Pharmacology and Dependence in Mice.

Shakir D Alsharari, Justin R King, Jacob C Nordman, Pretal P Muldoon, Asti Jackson, Andy Z X Zhu, Rachel F Tyndale, Nadine Kabbani, M Imad Damaj

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

60 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. Article
  6. Continuous Nicotine Monitors for Personal Nicotine Pharmacokinetics: A Receptor-Aware Research Agenda.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025
    Review
  7. Antioxidant Properties ofCombinatorial chemistry & high throughput screening · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Differences in Cognitive Task Performance, Reinforcement Enhancement, and Nicotine Dependence Between Menthol and Nonmenthol Cigarette Smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2021
    Article
  17. Article
  18. Article
  19. Article
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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

9 authors at 4 institutions in 3 countries.

Shakir D AlsharariDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia; Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Justin R KingDepartment of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, United States of America.
Jacob C NordmanDepartment of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, United States of America.
Pretal P MuldoonDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Asti JacksonDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Andy Z X ZhuCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Department of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Rachel F TyndaleCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Department of Pharmacology and Toxicology, and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Nadine KabbaniDepartment of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia, United States of America.
M Imad DamajDepartment of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Virginia Commonwealth University Medical Center · USInstitute for Advanced Study · USUniversity of Toronto · CAGeorge Mason University · US

Funding

University of Toronto Coordinating Genetics Core & Clinical Trial SiteU01DA020830 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI LERMAN, CARYN, TYNDALE, RACHEL FYNVOLA · 2005 to 2014
$22.4M
TRAINING IN THE PHARMACOLOGY OF ABUSED DRUGST32DA007027 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI William L. Dewey · 1985 to 2026
$14.7M
VCU Center for Drug Addiction ResearchP30DA033934 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI JOLENE J WINDLE · 2014 to 2026
$13.8M
THE ROLE OF ENDOGENOUS OPIOIDS IN SUDDEN INFANT DEATHP50DA005274 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ABOOD, MARY E · 1988 to 2011
$12.6M
Cognitive and Behavioral Effects of Sleep Restriction in Adolescents with ADHDR03MH109787 · NIMH · CINCINNATI CHILDRENS HOSP MED CTR · PI BECKER, STEPHEN P · 2016 to 2017
$156k
CIHR MOP86471CIHR TMH109787NIDA NIH HHS DA020830NIDA NIH HHS DA-05274NIDA NIH HHS P30 DA033934NIDA NIH HHS P50 DA005274NIDA NIH HHS T32 DA007027NIDA NIH HHS U01 DA020830NIMH NIH HHS R03 MH109787
6 · The paper itself

Abstract

Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia) and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease) and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c.) for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of α4 and β2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in β2 and α4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of β2 and α4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile.

Indexed as

AnimalsBody TemperatureBrainFemaleHyperalgesiaHypothermia, InducedMaleMaze LearningMentholMice, Inbred ICRNicotineNociceptionReceptors, NicotinicSubstance Withdrawal SyndromeTime FactorsTobacco Use DisorderMentholNicotineReceptors, Nicotinic

Identifiers

PMID26355604
PMCPMC4565647
OpenAlexW2239614844

What OpenQuestion holds

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LicenceCC BY
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.