ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
A CHRNA5 Smoking Risk Variant Decreases the Aversive Effects of Nicotine in Humans.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Inhalation of Alcohol Vapor: Measurement and Implications.Alcoholism, clinical and experimental research · 2017Pooled it
- Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.Journal of studies on alcohol and drugs · 2016Pooled it
- Impact of delivery rate on the acute response to intravenous nicotine: A human laboratory study with implications for regulatory science.Addiction biology · 2022Trial
- Atomoxetine in abstinent cocaine users: Cognitive, subjective and cardiovascular effects.Pharmacology, biochemistry, and behavior · 2017Trial
- Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Trial
- Disruption ofiScience · 2026Article
- Nicotinic Receptors in the Medial Habenula to Interpeduncular Nucleus Pathway: Modulators of Reward, Aversion and Emotion.The European journal of neuroscience · 2025Review
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- Nicotine and neuronal nicotinic acetylcholine receptors: unraveling the mechanisms of nicotine addiction.Frontiers in neuroscience · 2025Review
- Perspectives on the α5 nicotinic acetylcholine receptor in lung cancer progression.Frontiers in cell and developmental biology · 2025Review
- Biochemical Diagnosis in Substance and Non-substance Addiction.Advances in experimental medicine and biology · 2025Review
- Smoking-Related Increases in Alcohol Outcomes and Preliminary Evidence for the Protective Effect of a Functional Nicotine Receptor Gene (CHRNA5) Variant on Alcohol Consumption in Individuals Without Alcohol Use Disorder.The international journal of neuropsychopharmacology · 2024Article
- The Role of Nicotine Metabolic Rate on Nicotine Dependence and Rewarding: Nicotine Metabolism in Chinese Male Smokers and Male Mice.Molecular neurobiology · 2024Article
- AIGen: an artificial intelligence software for complex genetic data analysis.Briefings in bioinformatics · 2024Article
- Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated With Heavy Smoking Under a Range of Nicotine Dosing Conditions.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Abundant extrasynaptic expression of α3β4-containing nicotinic acetylcholine receptors in the medial habenula-interpeduncular nucleus pathway in mice.Scientific reports · 2024Article
- CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer's disease.Translational psychiatry · 2024Article
- CHRNA5 gene variation affects the response of VTA dopaminergic neurons during chronic nicotine exposure and withdrawal.Neuropharmacology · 2023Article
- Examining racial differences in smoking outcomes among smokers enrolled in an intravenous nicotine infusion study.Addictive behaviors · 2023Article
- Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa).BMC medicine · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Genome-wide association studies have implicated the CHRNA5-CHRNA3-CHRNB4 gene cluster in risk for heavy smoking and several smoking-related disorders. The heavy smoking risk allele might reduce the aversive effects of nicotine, but this hypothesis has not been tested in humans. We evaluated the effects of a candidate causal variant in CHRNA5, rs16969968, on the acute response to nicotine in European American (EA) and African American (AA) smokers (n=192; 50% AA; 73% male). Following overnight abstinence from nicotine, participants completed a protocol that included an intravenous (IV) dose of saline and two escalating IV doses of nicotine. The outcomes evaluated were the aversive, pleasurable, and stimulatory ratings of nicotine's effects, cardiovascular reactivity to nicotine, withdrawal severity, and cognitive performance before and after the nicotine administration session. The heavy smoking risk allele (rs16969968*A; frequency=28% (EA) and 6% (AA)) was associated with lower ratings of aversive effects (P<5 × 10(-8)) with marked specificity. This effect was evident in EA and AA subjects analyzed as separate groups and was most robust at the highest nicotine dose. Rs16969968*A was also associated with greater improvement on a measure of cognitive control (Stroop Task) following nicotine administration. These findings support differential aversive response to nicotine as one likely mechanism for the association of CHRNA5-CHRNA3-CHRNB4 with heavy smoking.
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Registered trials
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.