Nicotine - Addiction/Dependence - Revision history

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Background Information

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	='''Background Information'''=		='''Background Information'''=

			===2011 [https://research.med.psu.edu/smoking/dependence-index/ Penn State Nicotine Dependence Index]===
			*The Penn State Nicotine Dependence Index was developed by Dr. Jonathan Foulds in 2011. This 10-item scale (with scores ranging from 0 to 20) was developed to measure nicotine dependence across all nicotine product types, and an adapted version was the first dependence measure designed to evaluate electronic cigarette dependence.

	===2009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798587/ Abuse liability assessment of tobacco products including potential reduced exposure products]===		===2009 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798587/ Abuse liability assessment of tobacco products including potential reduced exposure products]===
	*" In the 2009 law giving FDA regulation over tobacco products, FDA is now required to evaluate new tobacco products including MRTP/PREPs to determine their risk for abuse and toxicity at the population level. This article describes the traditional tools and methods of ALA that can be used to evaluate new tobacco and nicotine products including MRTP/PREPs. Such ALA data could contribute to the scientific foundation on which future public policy decisions are based."		*In the 2009 law giving FDA regulation over tobacco products, FDA is now required to evaluate new tobacco products including MRTP/PREPs to determine their risk for abuse and toxicity at the population level. This article describes the traditional tools and methods of ALA that can be used to evaluate new tobacco and nicotine products including MRTP/PREPs. Such ALA data could contribute to the scientific foundation on which future public policy decisions are based.
	**Citation: ~~Carter LP, Stitzer ML, Henningfield JE, O'Connor RJ, Cummings KM, Hatsukami DK~~. ~~Abuse liability assessment of tobacco products including potential reduced exposure products~~. ~~Cancer Epidemiol Biomarkers Prev. 2009 Dec;18(12)~~:~~3241~~-62. ~~doi~~: 10.~~1158~~/~~1055~~-~~9965.EPI~~-09-~~0948. PMID: 19959676; PMCID: PMC2798587.~~
	***Acknowledgment: Supported by National Cancer Institute contract N01-PC-64402 - Laboratory Assessment of Tobacco Use Behavior and Exposure to Toxins Among Users of New Tobacco Products. This article is ~~one in~~ a ~~series of articles on the methods and measures~~ for the ~~evaluation~~ of ~~potential reduced exposure products. Jack E~~. ~~Henningfield provides consulting support~~ to ~~GlaxoSmithKline Consumer Healthcare through Pinney Associates on~~ an ~~exclusive basis regarding tobacco~~ dependence treatment (GSK had no editorial input into this manuscript), has a financial interest in a potential new oral nicotine replacement therapy product, and serves an expert witness in litigation against the tobacco industry. ~~Dorothy Hatsukami has received a research grant from NabiBiopharmaceuticals to conduct a trial on~~ the ~~nicotine vaccine. Mike Cummnings has received payments as a paid expert witness for plaintiffs in litigation against~~ the ~~tobacco industry and consulting and/or speaker fees from Novartis Corporation (~~to ~~attend two meetings they have sponsored on the topic of smoking cessation)~~ and ~~Pfizer Corporation (to give talks to health professionals on the subject of smoking cessation). Maxine Stitzer has received funding from Pfizer for an investigator-initiated study~~.		===2003 [https://www.nature.com/articles/1300030 A Self-Administered Questionnaire to Measure Dependence on Cigarettes: The Cigarette Dependence Scale]===
			*The aim of this study was to develop a new, self-administered measure of cigarette dependence.

			===1991 [https://cde.nida.nih.gov/instrument/d7c0b0f5-b865-e4de-e040-bb89ad43202b Fagerstrom Test for Nicotine Dependence]===
			*The Fagerström Test for Nicotine Dependence is a standard instrument for assessing the intensity of physical addiction to nicotine. The test was designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. It contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence.

	='''Smoking - Combustible Tobacco'''=		='''Smoking - Combustible Tobacco'''=

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Added recommended video to info on top of page

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	'''<big><span style="background-color: rgb(255, 255, 0);" data-mce-style="background-color: #ffff00;">Recommended Podcast</span>: [https://www.thestudiesshowpod.com/p/episode-40-addiction The Studies Show Episode 40: Addiction]</big>'''		'''<big><span style="background-color: rgb(255, 255, 0);" data-mce-style="background-color: #ffff00;">Recommended Podcast</span>: [https://www.thestudiesshowpod.com/p/episode-40-addiction The Studies Show Episode 40: Addiction]</big>'''

			'''<big><span style="background-color: rgb(255, 255, 0);" data-mce-style="background-color: #ffff00;">Recommended Video</span>: [https://www.youtube.com/watch?v=Xwi-nRS4kjU Tobacco Addiction & Nicotine Dependency]
	<br>		<br>

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Suggestions to add to this page

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	='''Suggestions to add to this page'''=		='''Suggestions to add to this page'''=

			===2024: [https://osf.io/rf74g Chapter 26 Tobacco smoking addiction and nicotine dependence]===
			*Sharon Cox

	===2016 [https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2016.00126/full Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers]===		===2016 [https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2016.00126/full Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers]===

Skip: /* 2017 Evaluating nicotine dependence levels in e-cigarette users */

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2017 Evaluating nicotine dependence levels in e-cigarette users

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	**Citation: González Roz A, Secades Villa R, Weidberg S. Evaluating nicotine dependence levels in e-cigarette users. Adicciones. 2017 Jan 11;29(2):136-138. English, Spanish. doi: 10.20882/adicciones.905. PMID: 28170058.		**Citation: González Roz A, Secades Villa R, Weidberg S. Evaluating nicotine dependence levels in e-cigarette users. Adicciones. 2017 Jan 11;29(2):136-138. English, Spanish. doi: 10.20882/adicciones.905. PMID: 28170058.
	***Acknowledgment: Funding for this study was provided by the BBVA foundation (SV-14-FBBVA-1). This institution had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. No conflicts reported.		***Acknowledgment: Funding for this study was provided by the BBVA foundation (SV-14-FBBVA-1). This institution had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. No conflicts reported.

			===2017: [https://onlinelibrary.wiley.com/doi/abs/10.1111/add.14013 Evaluating the mutual pathways among electronic cigarette use, conventional smoking and nicotine dependence]===
			*Conclusion: "Nicotine dependence is not a significant mechanism for e-cigarettes’ purported effect on heavier future conventional smoking among young adults. Nicotine dependence may be a mechanism for increases in e-cigarette use among heavier conventional smokers, consistent with e-cigarettes as a smoking reduction tool. Overall, conventional smoking and, to a lesser extent, its resulting nicotine dependence, are the strongest drivers or signals of later cigarette and e-cigarette use."
			**Citation: Selya AS, Rose JS, Dierker L, Hedeker D, Mermelstein RJ. Evaluating the mutual pathways among electronic cigarette use, conventional smoking and nicotine dependence. Addiction. 2018 Feb;113(2):325-333. doi: 10.1111/add.14013. Epub 2017 Sep 25. PMID: 28841780; PMCID: PMC5760290.
			***Acknowledgment: Grants and funding, L40 DA042431/DA/NIDA NIH HHS/United States, P01 CA098262/CA/NCI NIH HHS/United States, P30 DK092949/DK/NIDDK NIH HHS/United States, P50 DA039838/DA/NIDA NIH HHS/United States

	===2017 [https://pubmed.ncbi.nlm.nih.gov/28780356/ Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes]===		===2017 [https://pubmed.ncbi.nlm.nih.gov/28780356/ Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes]===

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2018 Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes

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	**Citation: Browne M, Todd DG. Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes. Addict Behav. 2018 Jan;76:113-121. doi: 10.1016/j.addbeh.2017.07.034. Epub 2017 Jul 28. PMID: 28780356.		**Citation: Browne M, Todd DG. Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes. Addict Behav. 2018 Jan;76:113-121. doi: 10.1016/j.addbeh.2017.07.034. Epub 2017 Jul 28. PMID: 28780356.
	***Acknowledgement: Research was supported by block funding to the School of Health, Medical and Applied Sciences, Central Queensland University		***Acknowledgement: Research was supported by block funding to the School of Health, Medical and Applied Sciences, Central Queensland University

			===2018: [https://pubmed.ncbi.nlm.nih.gov/29065204/ The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction]===
			*"These findings offer possible support that e-cigarettes may act as a smoking reduction method among highly nicotine-dependent young adult cigarette smokers."
			**Citation: Selya AS, Dierker L, Rose JS, Hedeker D, Mermelstein RJ. The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction. Nicotine Tob Res. 2018 Sep 4;20(10):1272-1277. doi: 10.1093/ntr/ntx160. PMID: 29065204; PMCID: PMC6121914.
			***Acknowledgment: Grants and funding, P01 CA098262/CA/NCI NIH HHS/United States, P50 DA039838/DA/NIDA NIH HHS/United States

	===2017 [https://pubmed.ncbi.nlm.nih.gov/28389330/ A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study]===		===2017 [https://pubmed.ncbi.nlm.nih.gov/28389330/ A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study]===

Skip: /* 2015 Explaining the effects of electronic cigarettes on craving for tobacco in recent quitters */

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2015 Explaining the effects of electronic cigarettes on craving for tobacco in recent quitters

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	**Citation: Etter JF. Explaining the effects of electronic cigarettes on craving for tobacco in recent quitters. Drug Alcohol Depend. 2015 Mar 1;148:102-8. doi: 10.1016/j.drugalcdep.2014.12.030. Epub 2015 Jan 3. PMID: 25592454.		**Citation: Etter JF. Explaining the effects of electronic cigarettes on craving for tobacco in recent quitters. Drug Alcohol Depend. 2015 Mar 1;148:102-8. doi: 10.1016/j.drugalcdep.2014.12.030. Epub 2015 Jan 3. PMID: 25592454.
	***Acknowledgment: This study was partly funded by the Swiss Tobacco Prevention Fund (Swiss Federal Office of Public Health), grant 12.000189 to JFE. The Swiss Tobacco Prevention Fund had no role in the design or conduct of the study, interpretation of the data or decision to submit the paper for publication... JFE was reimbursed by Dekang, a manufacturer of e-cigarettes and e-liquids for traveling to London and to China, to visit e-cigarette factories, but he received no honoraria for these meetings. JFE's salary is paid by the University of Geneva... Vincent Baujard, from the HON Foundation, Geneva, Switzerland developed the software for data collection. Thomas Eissenberg (Virginia Commonwealth University, USA), was a consultant for this study...		***Acknowledgment: This study was partly funded by the Swiss Tobacco Prevention Fund (Swiss Federal Office of Public Health), grant 12.000189 to JFE. The Swiss Tobacco Prevention Fund had no role in the design or conduct of the study, interpretation of the data or decision to submit the paper for publication... JFE was reimbursed by Dekang, a manufacturer of e-cigarettes and e-liquids for traveling to London and to China, to visit e-cigarette factories, but he received no honoraria for these meetings. JFE's salary is paid by the University of Geneva... Vincent Baujard, from the HON Foundation, Geneva, Switzerland developed the software for data collection. Thomas Eissenberg (Virginia Commonwealth University, USA), was a consultant for this study...


	='''Heated Tobacco Product (HTP)'''=		='''Heated Tobacco Product (HTP)'''=

Skip: /* 2021 Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use */

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2021 Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use

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	===2021 [https://onlinelibrary.wiley.com/doi/10.1111/add.15403 Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use]===		===2021 [https://onlinelibrary.wiley.com/doi/10.1111/add.15403 Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use]===
	*Among US high school students, increases in the prevalence of nicotine product use from 2012 to 2019 do not appear to have been accompanied by a similar increase in the population burden of nicotine dependence. This may be at least partly attributable to a shift in the most common product of choice from cigarettes (on which users are most dependent) to e-cigarettes (on which users are least dependent).		*Among US high school students, increases in the prevalence of nicotine product use from 2012 to 2019 do not appear to have been accompanied by a similar increase in the population burden of nicotine dependence. This may be at least partly attributable to a shift in the most common product of choice from cigarettes (on which users are most dependent) to e-cigarettes (on which users are least dependent).
			*Use of e-cigarettes increased dramatically, use of cigarettes declined, and use of combustible (non-cigarette) and smokeless tobacco was relatively stable. Whether the overall increase in product use has been mirrored by an increase in nicotine dependence was unclear.
			*We found that different tobacco products were associated with differing levels of nicotine dependence, with cigarettes characterised by highest dependence and e-cigarettes in otherwise tobacco-naïve students by low dependence.
			*The increase in population use of tobacco products between 2012 and 2019 (from 23.2% to 31.2%) was not accompanied by an equivalent increase in overall population burden of dependence (craving: 10.9% to 9.5%; wanting to use within 30min: 4.7% to 5.4%).
	*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.15403 PDF Version]		*[https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.15403 PDF Version]
			*[[File:Youth_Dependence.jpg\|Youth Dependence on Nicotine Products]]
	**Citation: Jackson, S. E., Brown, J., and Jarvis, M. J. (2021) Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use. Addiction, 116: 1859– 1870. doi: 10.1111/add.15403		**Citation: Jackson, S. E., Brown, J., and Jarvis, M. J. (2021) Dependence on nicotine in US high school students in the context of changing patterns of tobacco product use. Addiction, 116: 1859– 1870. doi: 10.1111/add.15403
	**Acknowledgement: Cancer Research UK (C1417/A22962) supported S.J. andJ.B.’s salaries.		***Acknowledgement: Cancer Research UK (C1417/A22962) supported S.J. andJ.B.’s salaries.

	===2021 [https://pubmed.ncbi.nlm.nih.gov/33894800/ Changes in Dependence as Smokers Switch from Cigarettes to JUUL in Two Nicotine Concentrations]===		===2021 [https://pubmed.ncbi.nlm.nih.gov/33894800/ Changes in Dependence as Smokers Switch from Cigarettes to JUUL in Two Nicotine Concentrations]===

Skip: /* 2015 Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes */

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2015 Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes

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	**Citation: Etter JF, Eissenberg T. Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes. Drug Alcohol Depend. 2015 Feb 1;147:68-75. doi: 10.1016/j.drugalcdep.2014.12.007. Epub 2014 Dec 18. PMID: 25561385; PMCID: PMC4920051.		**Citation: Etter JF, Eissenberg T. Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes. Drug Alcohol Depend. 2015 Feb 1;147:68-75. doi: 10.1016/j.drugalcdep.2014.12.007. Epub 2014 Dec 18. PMID: 25561385; PMCID: PMC4920051.
	***This study was partly funded by the Swiss Tobacco Prevention Fund (Swiss Federal Office of Public Health), grant 12.000189 to JFE. The Swiss Tobacco Prevention Fund had no role in the design or conduct of the study, interpretation of the data or decision to submit the paper for publication. TE is supported by the National Institute on Drug Abuse of the U.S. National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.		***This study was partly funded by the Swiss Tobacco Prevention Fund (Swiss Federal Office of Public Health), grant 12.000189 to JFE. The Swiss Tobacco Prevention Fund had no role in the design or conduct of the study, interpretation of the data or decision to submit the paper for publication. TE is supported by the National Institute on Drug Abuse of the U.S. National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.

			===2012 [https://ncbi.nlm.nih.gov/pmc/articles/PMC3330136/ Clinical laboratory assessment of the abuse liability of an electronic cigarette]===
			*Conclusion: Electronic cigarettes can deliver clinically significant amounts of nicotine and reduce cigarette abstinence symptoms and appear to have lower potential for abuse relative to traditional tobacco cigarettes, at least under certain laboratory conditions.
			**Citation:Vansickel AR, Weaver MF, Eissenberg T. Clinical laboratory assessment of the abuse liability of an electronic cigarette. Addiction. 2012 Aug;107(8):1493-500. doi: 10.1111/j.1360-0443.2012.03791.x. Epub 2012 May 8. PMID: 22229871; PMCID: PMC3330136.
			***Acknowledgment: This work was partially funded by the National Cancer Institute, National Institutes of Health RO1CA 120142 (awarded to Dr. Eissenberg). Dr. Vansickel was supported by National Institute on Drug Abuse, National Institutes of Health T32DA 007027. The authors have no conflicts of interest to declare.

	='''ENDS/E-Cigarettes/NVP/Vaping - Not Compared with Smoking Tobacco'''=		='''ENDS/E-Cigarettes/NVP/Vaping - Not Compared with Smoking Tobacco'''=

Skip: /* 2017 A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study */

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2017 A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study

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	**Citation: Stiles MF, Campbell LR, Jin T, Graff DW, Fant RV, Henningfield JE. Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum. Psychopharmacology (Berl). 2018 Jul;235(7):2077-2086. doi: 10.1007/s00213-018-4904-x. Epub 2018 May 3. PMID: 29725702; PMCID: PMC6015619.		**Citation: Stiles MF, Campbell LR, Jin T, Graff DW, Fant RV, Henningfield JE. Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum. Psychopharmacology (Berl). 2018 Jul;235(7):2077-2086. doi: 10.1007/s00213-018-4904-x. Epub 2018 May 3. PMID: 29725702; PMCID: PMC6015619.
	***Acknowledgement: ClinicalTrials.gov identifier: NCT02664012. MF Stiles, LR Campbell, and T Jin are full-time employees of RAI Services Company. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is a wholly owned subsidiary of British American Tobacco plc. DW Graff is a full-time employee of Celerion and provided the original draft of the manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on smoking cessation and tobacco harm minimization (including nicotine replacement therapy and electronic vapor products) to Niconovum, USA, Inc., RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.). JE Henningfield also owns an interest in intellectual property for a novel nicotine medication. Through PinneyAssociates, Fant and Henningfield provide consulting services to pharmaceutical companies on abuse potential assessment, and the regulation of substances with a potential for abuse.		***Acknowledgement: ClinicalTrials.gov identifier: NCT02664012. MF Stiles, LR Campbell, and T Jin are full-time employees of RAI Services Company. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is a wholly owned subsidiary of British American Tobacco plc. DW Graff is a full-time employee of Celerion and provided the original draft of the manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on smoking cessation and tobacco harm minimization (including nicotine replacement therapy and electronic vapor products) to Niconovum, USA, Inc., RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.). JE Henningfield also owns an interest in intellectual property for a novel nicotine medication. Through PinneyAssociates, Fant and Henningfield provide consulting services to pharmaceutical companies on abuse potential assessment, and the regulation of substances with a potential for abuse.

			===2018 [https://www.sciencedirect.com/science/article/abs/pii/S0306460317302885 Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes]===
			*Conclusion: "First, we found that the large majority of vapers were ex-smokers who had either ceased or dramatically reduced their cigarette consumption. Second, there was a marked decrease in dependence among vapers compared to their retrospective prior cigarette dependence..."
			*[https://sci-hub.st/10.1016/j.addbeh.2017.07.034 PDF of full study]
			**Citation: Browne M, Todd DG. Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes. Addict Behav. 2018 Jan;76:113-121. doi: 10.1016/j.addbeh.2017.07.034. Epub 2017 Jul 28. PMID: 28780356.
			***Acknowledgement: Research was supported by block funding to the School of Health, Medical and Applied Sciences, Central Queensland University

	===2017 [https://pubmed.ncbi.nlm.nih.gov/28389330/ A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study]===		===2017 [https://pubmed.ncbi.nlm.nih.gov/28389330/ A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study]===

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Heated Tobacco Product (HTP)

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 **Citation: Etter JF, Eissenberg T. Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes. Drug Alcohol Depend. 2015 Feb 1;147:68-75. doi: 10.1016/j.drugalcdep.2014.12.007. Epub 2014 Dec 18. PMID: 25561385; PMCID: PMC4920051.
 ***This study was partly funded by the Swiss Tobacco Prevention Fund (Swiss Federal Office of Public Health), grant 12.000189 to JFE. The Swiss Tobacco Prevention Fund had no role in the design or conduct of the study, interpretation of the data or decision to submit the paper for publication. TE is supported by the National Institute on Drug Abuse of the U.S. National Institutes of Health under Award Number P50DA036105 and the Center for Tobacco Products of the U.S. Food and Drug Administration. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.
 ='''Heated Tobacco Product (HTP)'''=
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 *"These findings suggest that the abuse liability of the THPs lies between that of subjects usual brand cigarettes and the NRT."
 **Citation: Hardie G, Gale N, McEwan M, Oscar SM, Ziviani L, Proctor CJ, Murphy J. An abuse liability assessment of the glo tobacco heating product in comparison to combustible cigarettes and nicotine replacement therapy. Sci Rep. 2022 Aug 29;12(1):14701. doi: 10.1038/s41598-022-19167-8. Erratum in: Sci Rep. 2023 Jun 27;13(1):10441. doi: 10.1038/s41598-023-37432-2. PMID: 36038580; PMCID: PMC9424205.
 ***Acknowledgment: The study was funded in full by British American Tobacco (Investments) Limited (BAT). GH, NG, and MMcE are current employees of BAT. JM was an employee of BAT at the time of the study conduct and is currently an employee of R. J. Reynolds Tobacco Company, a subsidiary of BAT. CJP was an employee of BAT at the time of study conduct and is currently contracted to BAT to provide consultancy on tobacco product science and regulation. SM and LZ are employees of CRC, the clinic who performed the trial.
 ='''Nicotine Pouches'''=