학술논문
Evaluating the Role of Nicotine Stereoisomer on Nicotine Pouch Abuse Liability: A Randomized Crossover Trial.
Document Type
Academic Journal
Author
Keller-Hamilton B; Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; Curran H; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; Alalwan M; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; Hinton A; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; Brinkman MC; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; College of Public Health, The Ohio State University, Columbus, OH, USA.; El-Hellani A; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; College of Public Health, The Ohio State University, Columbus, OH, USA.; Wagener TL; Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; Chrzan K; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; College of Public Health, The Ohio State University, Columbus, OH, USA.; Atkinson L; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; College of Public Health, The Ohio State University, Columbus, OH, USA.; Suraapaneni S; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.; Mays D; Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.; Comprehensive Cancer Center, Center for Tobacco Research, The Ohio State University, Columbus, OH, USA.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 9815751 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-994X (Electronic) Linking ISSN: 14622203 NLM ISO Abbreviation: Nicotine Tob Res Subsets: MEDLINE
Subject
Language
English
Abstract
Introduction: Many 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 Methods: N = 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.
Results: Using 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.
Conclusions: Participants 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.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Aims and Methods: N = 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.
Results: Using 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.
Conclusions: Participants 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.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)