Trial reportNicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco2020
The Relationship of Varenicline Agonism of α4β2 Nicotinic Acetylcholine Receptors and Nicotine-Induced Dopamine Release in Nicotine-Dependent Humans.
Trial report in Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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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.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Recent cannabis exposure and acute nicotine effects: insights from randomized, double-blind, placebo-controlled intravenous nicotine studies.The international journal of neuropsychopharmacology · 2026Trial
- Metabolomic and biochemical evaluation of linalool and methyl eugenol as natural alternatives to varenicline in nicotine-induced metabolic dysfunction.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Nicotinic Acetylcholine Receptor Pathways in Cancer: From Psychiatric Clues to Therapeutic Opportunities.Cancer reports (Hoboken, N.J.) · 2025Review
- Cholinergic network modulation in disinhibited eating behavior.Communications biology · 2025Article
- Cholinergic tone abnormalities and relationships with smoking severity in human cigarette smokers: exploratory positron emission tomography study using [Molecular psychiatry · 2025Article
- Single-Cell Profiling Identifies Reward Behavior-Related Neurons and Alterations in the Ventral Tegmental Area Based onResearch (Washington, D.C.) · 2025Article
- Smoking, Obesity, and Post-Cessation Weight Gain: Neurobiological Intersection and Treatment Recommendations.Journal of multidisciplinary healthcare · 2025Review
- Article
- An overview of traditional smoking cessation interventions and E-cigarettes.Frontiers in pharmacology · 2024Review
- Imaging Cholinergic Receptors in the Brain by Positron Emission Tomography.Journal of medicinal chemistry · 2023Review
- Article
- Addiction-related neuroadaptations following chronic nicotine exposure.Journal of neurochemistry · 2021Review
- Tobacco Smoking and LiverJournal of oncology · 2021Review
- Safety of varenicline as an aid to smoking cessation in professional drivers and its impact on driving behaviors: An observational cohort study of taxi drivers in Beijing.Tobacco induced diseases · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
introductionCigarette smoking continues to be one of the most important behavioral causes of morbidity and mortality in the world. Varenicline, an α4β2 nicotinic acetylcholine receptor (nAChR) partial agonist, has been shown to increase smoking quit rates compared with nicotine-based products. This human laboratory, double-blind, placebo-controlled study examined varenicline and placebo effects on α4β2-nAChRs occupancy, nicotine-induced change in [11C]raclopride non-displaceable binding potential (BPND), and behavioral measures of cigarette smoking, nicotine craving, and withdrawal.
methodsCurrent nicotine dependent daily smokers (N = 17) were randomized to varenicline 1 mg twice daily or placebo for 13 days. Using positron emission tomography), we characterized α4β2-nAChRs occupancy using [18F]AZAN and dopamine receptor binding using [11C]raclopride as well as behavioral measures of cigarettes smoked, craving, and nicotine withdrawal.
resultsVarenicline compared with placebo resulted in significant reductions in [18F]AZAN BPND in multiple brain regions including thalamus, midbrain, putamen, and ventral striatum. Following administration of a controlled-dose nicotine cigarette, dopamine release was significantly suppressed in the ventral striatum in the varenicline-treated compared with the placebo group. There was a significant relationship between α4β2-nAChRs BPND measured in thalamus during the [18F]AZAN scan and nicotine-induced change in raclopride BPND in the ventral striatum.
conclusionThis is the first human study to demonstrate a direct relationship between the extent of varenicline occupancy of α4β2-nAChRs and the magnitude of dopamine release following nicotine use. IMPLICATIONS: It has remained unclear how nicotinic receptor blockade through partial agonist medications such as varenicline promotes smoking cessation. One hypothesized mechanism is downstream dampening of the mesolimbic reward dopamine system. For the first time in human smokers, we observed a direct relationship between the extent of varenicline blockade of α4β2-nACh nicotinic receptors and the magnitude of dopamine release following smoking. This has mechanistic and therapeutic implications for improving smoking cessation interventions.
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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.