Trial reportNicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco2025
Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial.
Trial report in Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05236894 (Examining the Appeal of Nicotine Pouches in Ohio Appalachia), which is not on this map. Cited by 5 papers.
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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.
Examining the Appeal of Nicotine Pouches in Ohio Appalachia
Who cites it
5 citing papers in PubMed.
- Single-cell transcriptomics reveals distinct microglial state remodeling associated with the (R)-nicotine/diosmetin combination and galantamine in LPS-challenged BV2 cells.Frontiers in immunology · 2026Article
- Prospective associations between nicotine type and the continuation of youth e-cigarette use.BMC public health · 2025Article
- Examining the role of freebase nicotine in the harm reduction potential of oral nicotine pouches versus moist snuff: A randomized crossover trial.Addiction (Abingdon, England) · 2025Article
- A comprehensive review on oral nicotine pouches: Available scientific evidence and future research needs.Experimental and clinical psychopharmacology · 2025Review
- Testing oral nicotine pouches versus nicotine replacement therapy for cigarette harm reduction in Appalachia: The ARISE study protocol.PloS one · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
introductionMany oral nicotine pouch (ONP) brands use synthetic nicotine, which typically contains a racemic (50:50) mixture of nicotine's two stereoisomers: S-nicotine and R-nicotine. Because tobacco-derived nicotine contains more than 99% S-nicotine, the effects of R-nicotine in humans are not well known. We compared systemic nicotine exposure and product appeal of ONPs containing more than 99% S-nicotine versus racemic nicotine. AIMS AND
methodsN = 18 adult smokers (Mage = 45 years, 66.7% male, 77.8% White) enrolled in a three-visit single-blind, randomized crossover study. During each visit, participants used one wintergreen-flavored, 3 mg nicotine ONP for 30 min following at least12 h nicotine abstinence. Study ONP #1 contained more than 99% S-nicotine and the other two study ONPs contained racemic nicotine (collapsed for analyses). Plasma nicotine assessments and measures of withdrawal relief occurred at t = 0, 5, 15, 30, 60, and 90 min; measures of product appeal were assessed following ONP use.
resultsUsing the ONP with more than 99% S-nicotine resulted in greater plasma nicotine concentration from 15 to 90 min (p < .0001) and greater maximum plasma nicotine concentration than the ONPs with racemic nicotine (M = 9.9 ng/mL [SD = 2.5] vs. M = 5.7 ng/mL [SD = 2.8], respectively; p < .0001). Product liking and withdrawal relief were similar across ONPs, although participants reported more "bad effects" when using the ONP with more than 99% S-nicotine.
conclusionsParticipants reported few subjective differences in ONPs according to nicotine stereoisomer, but plasma nicotine concentration was greater for ONPs using more than 99% S-nicotine. ONPs with more than 99% S-nicotine (vs. racemic nicotine) might be better substitutes for cigarettes, but research into other ONP characteristics (eg flavors, freebase nicotine) is needed to inform regulation. IMPLICATIONS: Little is known about the effects of racemic (vs. S-) nicotine in humans. In a sample of adults who smoke cigarettes, we identified that oral nicotine pouches containing racemic nicotine exposed participants to less nicotine than oral nicotine pouches containing only S-nicotine, but both types of oral nicotine pouches held similar, moderate appeal. Additional research evaluating the roles that flavorings, total nicotine concentration, and freebase nicotine play in the abuse liability of oral nicotine pouches would inform comprehensive product regulations to support public health.
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