Nicotine - Addiction/Dependence: Difference between revisions

 
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''' <big><span style="background-color: rgb(255, 255, 0);" data-mce-style="background-color: #ffff00;">[https://pubmed.ncbi.nlm.nih.gov/35302289/ Abuse Liability]</span>: The potential to develop a dependence or addiction to a substance.</big>'''
''' <big><span style="background-color: rgb(255, 255, 0);" data-mce-style="background-color: #ffff00;">[https://pubmed.ncbi.nlm.nih.gov/35302289/ Abuse Liability]</span>: The potential to develop a dependence or addiction to a substance.</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>'''
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='''Background Information'''=
===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."
**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.


='''Smoking - Combustible Tobacco'''=
='''Smoking - Combustible Tobacco'''=
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***Acknowledgment: The authors have declared that no competing interests exist. (No funding mentioned.)
***Acknowledgment: The authors have declared that no competing interests exist. (No funding mentioned.)


===2023 [https://pubmed.ncbi.nlm.nih.gov/36994368/ Shiffman S, Goldenson NI. Changes in dependence over one year among US adults who smoke cigarettes and switched completely or partially to use of the JUUL-brand electronic nicotine delivery system. Drug Alcohol Depend Rep. 2023 Jan 26;6:100137. doi: 10.1016/j.dadr.2023.100137. PMID: 36994368; PMCID: PMC10040328.]===
===2023 [https://pubmed.ncbi.nlm.nih.gov/36994368/ Changes in dependence over one year among US adults who smoke cigarettes and switched completely or partially to use of the JUUL-brand electronic nicotine delivery system]===
*Conclusion: "In this longitudinal study of US adults who smoked cigarettes and switched completely or partially to JUUL, dependence on JUUL was lower than baseline dependence on cigarettes after a year of JUUL use among participants who smoked every day at baseline. Observed increases in JUUL dependence over 12 months of JUUL use were statistically significant but small in magnitude—lower than the estimated minimal important difference—suggesting that dependence on JUUL did not meaningfully increase over a 1-year period. Additional longitudinal data over longer periods of time is needed to more completely address trajectories of dependence on ENDS, including JUUL."
*Conclusion: "In this longitudinal study of US adults who smoked cigarettes and switched completely or partially to JUUL, dependence on JUUL was lower than baseline dependence on cigarettes after a year of JUUL use among participants who smoked every day at baseline. Observed increases in JUUL dependence over 12 months of JUUL use were statistically significant but small in magnitude—lower than the estimated minimal important difference—suggesting that dependence on JUUL did not meaningfully increase over a 1-year period. Additional longitudinal data over longer periods of time is needed to more completely address trajectories of dependence on ENDS, including JUUL."
**Citation: Shiffman S, Goldenson NI. Changes in dependence over one year among US adults who smoke cigarettes and switched completely or partially to use of the JUUL-brand electronic nicotine delivery system. Drug Alcohol Depend Rep. 2023 Jan 26;6:100137. doi: 10.1016/j.dadr.2023.100137. PMID: 36994368; PMCID: PMC10040328.
**Citation: Shiffman S, Goldenson NI. Changes in dependence over one year among US adults who smoke cigarettes and switched completely or partially to use of the JUUL-brand electronic nicotine delivery system. Drug Alcohol Depend Rep. 2023 Jan 26;6:100137. doi: 10.1016/j.dadr.2023.100137. PMID: 36994368; PMCID: PMC10040328.
***Acknowledgment: The study was funded by Juul Labs, Inc. SS is a senior advisor to PinneyAssociates, Inc, through which he provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc. NIG is a full-time employee of Juul Labs, Inc. The authors would like to acknowledge the Centre for Substance Use Research (CSUR), an independent research consultancy, for designing the ADJUSST study and collecting the data used in this manuscript.
***Acknowledgment: The study was funded by Juul Labs, Inc. SS is a senior advisor to PinneyAssociates, Inc, through which he provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc. NIG is a full-time employee of Juul Labs, Inc. The authors would like to acknowledge the Centre for Substance Use Research (CSUR), an independent research consultancy, for designing the ADJUSST study and collecting the data used in this manuscript.
===2023 [https://pubmed.ncbi.nlm.nih.gov/36852436/ Nicotine Dependence among Current Cigarette Smokers Who Use E-Cigarettes and Cannabis]===
*"Results: In the sample, 27.6% were cigarette-only smokers, 24.8% were CIG-ECIG, 27.6% were CIG-CAN, and 20.0% were CIG-ECIG-CAN co-users. Significant differences were observed in sociodemographic and tobacco/other substance use characteristics by co-use status. E-cigarette co-users had low e-cigarette dependence, but moderate FTND scores. In adjusted analyses, only CIG-ECIG co-use was associated with higher FTND scores compared to cigarette-only smoking. However, CIG-ECIG and CIG-ECIG-CAN co-use were associated with higher FTND scores compared to CIG-CAN co-use."
**Citation: Jones DM, Guy MC, Fairman BJ, Soule E, Eissenberg T, Fagan P. Nicotine Dependence among Current Cigarette Smokers Who Use E-Cigarettes and Cannabis. Subst Use Misuse. 2023;58(5):618-628. doi: 10.1080/10826084.2023.2177961. Epub 2023 Feb 27. PMID: 36852436; PMCID: PMC10249428.
***Acknowledgment: Funding; K01 DA055088/DA/NIDA NIH HHS/United States and U54 DA036105/DA/NIDA NIH HHS/United States. COI; Thomas Eissenberg is a paid consultant in litigation against the tobacco industry and also the electronic cigarette industry and is named on one patent for a device that measures the puffing behavior of electronic cigarette users, on another patent application for a smartphone app that determines electronic cigarette device and liquid characteristics, and a third patent application for a smoking cessation intervention. Eric Soule is named on a patent application for a smartphone app that determines electronic cigarette device and liquid characteristics. The other authors declare they have no conflicts of interest.
===2022 [https://pubmed.ncbi.nlm.nih.gov/35305014/ The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review]===
*"Implications: E-cigarettes may provide a reduced-harm alternative to cigarettes for smokers unwilling/unable to quit or serve as a path for quitting all nicotine products. Higher nicotine concentrations and flavor variety are associated with higher abuse potential and appeal of e-cigarettes. Higher abuse potential and appeal products may help facilitate complete switching from cigarettes to e-cigarettes. Regulation of nicotine concentration and flavors aimed at decreasing naïve uptake may inadvertently decrease uptake and complete switching among smokers, reducing the harm reduction potential of e-cigarettes. Evidence-based effects of regulating nicotine concentration and flavors must be considered for the population as a whole, including smokers."
**Citation: Gades MS, Alcheva A, Riegelman AL, Hatsukami DK. The Role of Nicotine and Flavor in the Abuse Potential and Appeal of Electronic Cigarettes for Adult Current and Former Cigarette and Electronic Cigarette Users: A Systematic Review. Nicotine Tob Res. 2022 Aug 6;24(9):1332-1343. doi: 10.1093/ntr/ntac073. PMID: 35305014; PMCID: PMC9356694.
***Acknowledgment: This work was supported by the National Institute of Drug Abuse (T32 DA007097 and R36 DA050000 to MSG); and the National Institutes of Health (P01 CA217806 to DKH). No COI declared.
===2022 [https://pubmed.ncbi.nlm.nih.gov/36543869/ Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum]===
*"These data reinforce previous research and provide the scientific evidence to support regulatory decisions demonstrating that Vuse Solo has an AL profile lower than that of combustible cigarettes but higher than that of nicotine gum and, therefore, may be a suitable replacement for cigarette smoking for some adult smokers."
**Citation: Campbell C, Jin T, Round EK, Schmidt E, Nelson P, Baxter S. Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum. Sci Rep. 2022 Dec 21;12(1):22080. doi: 10.1038/s41598-022-26417-2. PMID: 36543869; PMCID: PMC9772348.
***Acknowledgment: C.C., T.J., E.S., E.R., and S.B. are full-time employees of RAI Services Company, and P.N. is a former full-time employee of RAI Services Company. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is an indirect, wholly owned subsidiary of British American Tobacco plc.
===2021 [https://pubmed.ncbi.nlm.nih.gov/33118854/ Dependence and Use Characteristics of Adult JUUL Electronic Cigarette Users]===
*"Conclusions: On average, JUUL users reported low to medium nicotine dependence on the PSECDI. JUUL user dependence may be more similar to e-cig user dependence than cigarette smoker dependence. These preliminary findings should be followed up in studies of larger samples of Juul users, collecting multiple measures of dependence, as well as biomarkers of nicotine intake (e.g. cotinine)."
**Citation: Yingst J, Foulds J, Hobkirk AL. Dependence and Use Characteristics of Adult JUUL Electronic Cigarette Users. Subst Use Misuse. 2021;56(1):61-66. doi: 10.1080/10826084.2020.1834582. Epub 2020 Oct 29. PMID: 33118854; PMCID: PMC7905831.
***Acknowledgment: Funding; This study was funded by internal funds provided by the Penn State College of Medicine Department of Psychiatry. ALH is supported by a career development award from the National Institute on Drug Abuse (K23 DA045081). JY and JF are supported by NIH grants (R01 DA048428, U01 DA045517). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. COI; JF has done paid consulting for pharmaceutical companies involved in producing smoking cessation medications, including GSK, Pfizer, Novartis, J&J, and Cypress Bioscience. The other authors have no disclosures to report related to this publication.


===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]===  
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**Citation: Rhoades DA, Comiford AL, Dvorak JD, Ding K, Hopkins M, Spicer P, Wagener TL, Doescher MP. Vaping patterns, nicotine dependence and reasons for vaping among American Indian dual users of cigarettes and electronic cigarettes. BMC Public Health. 2019 Sep 2;19(1):1211. doi: 10.1186/s12889-019-7523-5. PMID: 31477072; PMCID: PMC6721166.
**Citation: Rhoades DA, Comiford AL, Dvorak JD, Ding K, Hopkins M, Spicer P, Wagener TL, Doescher MP. Vaping patterns, nicotine dependence and reasons for vaping among American Indian dual users of cigarettes and electronic cigarettes. BMC Public Health. 2019 Sep 2;19(1):1211. doi: 10.1186/s12889-019-7523-5. PMID: 31477072; PMCID: PMC6721166.
***Acknowledgment: Grants from the National Cancer Institute of the National Institutes of Health (P20CA202921 to University of Oklahoma, and 5P20CA202923 to Cherokee Nation) supported this study. The funding body had no role in the design of the study and collection, analysis, interpretation of data, or writing the manuscript. Content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or of Cherokee Nation. The authors declare that they have no competing interests.
***Acknowledgment: Grants from the National Cancer Institute of the National Institutes of Health (P20CA202921 to University of Oklahoma, and 5P20CA202923 to Cherokee Nation) supported this study. The funding body had no role in the design of the study and collection, analysis, interpretation of data, or writing the manuscript. Content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or of Cherokee Nation. The authors declare that they have no competing interests.
===2019 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754311/ Abuse liability assessment of an electronic cigarette in combustible cigarette smokers]===
*"Collectively, the results of this study demonstrated that the ECIG device and liquids examined had moderate levels of abuse liability: on average lower than combustible cigarettes, but higher than an FDA-approved nicotine replacement therapy (i.e., nicotine inhaler)."
**Citation: Maloney SF, Breland A, Soule EK, Hiler M, Ramôa C, Lipato T, Eissenberg T. Abuse liability assessment of an electronic cigarette in combustible cigarette smokers. Exp Clin Psychopharmacol. 2019 Oct;27(5):443-454. doi: 10.1037/pha0000261. Epub 2019 Feb 18. PMID: 30777773; PMCID: PMC6754311.
***Acknowledgment: Funding; This study was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and U54DA036105 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. COI; Dr. Eissenberg is a paid consultant in litigation against the tobacco industry and is named on a patent for a device that measures the puffing behavior of ECIG users.


===2019 [https://pubmed.ncbi.nlm.nih.gov/31375364/ Changes in E-Cigarette Use Behaviors and Dependence in Long-term E-Cigarette Users]===  
===2019 [https://pubmed.ncbi.nlm.nih.gov/31375364/ Changes in E-Cigarette Use Behaviors and Dependence in Long-term E-Cigarette Users]===  
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**Citation: Liu G, Wasserman E, Kong L, Foulds J. A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study. Prev Med. 2017 Nov;104:86-91. doi: 10.1016/j.ypmed.2017.04.001. Epub 2017 Apr 4. PMID: 28389330; PMCID: PMC5868349.
**Citation: Liu G, Wasserman E, Kong L, Foulds J. A comparison of nicotine dependence among exclusive E-cigarette and cigarette users in the PATH study. Prev Med. 2017 Nov;104:86-91. doi: 10.1016/j.ypmed.2017.04.001. Epub 2017 Apr 4. PMID: 28389330; PMCID: PMC5868349.
***Acknowledgement: This work was supported in part by the National Institute on Drug Abuse of the NIH and the Center for Tobacco Products of the FDA (P50-DA-036107) (Liu, Wasserman, Foulds) and by the National Center for Advancing Translational Sciences, NIH, through Grant UL1 TR000127 (Kong). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA.
***Acknowledgement: This work was supported in part by the National Institute on Drug Abuse of the NIH and the Center for Tobacco Products of the FDA (P50-DA-036107) (Liu, Wasserman, Foulds) and by the National Center for Advancing Translational Sciences, NIH, through Grant UL1 TR000127 (Kong). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA.
===2017 [https://pubmed.ncbi.nlm.nih.gov/28170058/ Evaluating nicotine dependence levels in e-cigarette users]===
*Conclusion: "Results showed that e-cigarette users scored lower than cigarette smokers in both FTND and all NDSS subscales. Our findings extend previous research on e-cigarette use and nicotine addiction and suggest that e-cigarette users are less dependent on nicotine than current tobacco cigarette smokers."
**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.
===2017 [https://pubmed.ncbi.nlm.nih.gov/28780356/ Then and now: Consumption and dependence in e-cigarette users who formerly smoked cigarettes]===
*Conclusion: "Our results were largely consistent with expectations. 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. Finally, we also observed decoupling: a large attenuation of the relationship between dependence and consumption for vapers as compared to their retrospective prior smoking. We incorporated multiple measures of vaping consumption, which showed high variability with respect to a vapour volume/(negative) nicotine concentration continuum, with female and older vapers tending to vape at lower volumes combined with higher nicotine concentrations. However, the lack of reliability and unidimensionality of the FTND-V raise concerns about the adequacy of cigarette-analogous dependence measures for vaping, and whether ‘apples to apples’ comparisons with smoking are strictly valid. Finally, we observed no relationship between dependence or e-liquid volume consumption and duration of vaping. There was a tendency for those who have been vaping longer to employ increased nicotine concentration, but this was moderated by vapers' intentions to reduce their intake. Future research should focus on better measurement of consumption patterns and dependence indices for vaping, and employ these measures in prospective longitudinal designs."
**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. No conflicts of interest to declare.
===2017 [https://pubmed.ncbi.nlm.nih.gov/28634710/ Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability]===
*"In summary, this study is the most robust assessment of the abuse liability of ECs published to date and uses approaches similar to those found in classic abuse liability studies of pharmaceutical products, including multiple instruments to measure the subjective effects of product use, as well as nicotine uptake. Under the set of study conditions described herein, use of the three Vuse Solo ECs tended to result in subjective measures responses and nicotine uptake that were between those measured with use of combustible cigarettes and nicotine gum. In general, the results are consistent with the conclusions of others that the abuse liability of ECs as a category is less than that of combustible cigarettes but greater than for nicotine gum, and likely other nicotine replacement products'
**Citation: Stiles MF, Campbell LR, Graff DW, Jones BA, Fant RV, Henningfield JE. Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability. Psychopharmacology (Berl). 2017 Sep;234(17):2643-2655. doi: 10.1007/s00213-017-4665-y. Epub 2017 Jun 20. PMID: 28634710; PMCID: PMC5548902.
***Acknowledgment: Funding; This study was funded by RJ Reynolds Vapor Company through its affiliate RJ Reynolds Tobacco Company. COI; MF Stiles, LR Campbell, and BA Jones are full-time employees of RAI Services Company, which provides support across the Reynolds American Inc. operating companies. DW Graff is a full-time employee of Celerion and provided the original draft of this manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on tobacco harm minimization (including nicotine replacement therapy and digital vapor products) to Niconovum USA, RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.) In the past 3 years, PinneyAssociates has consulted to GlaxoSmithKline Consumer Healthcare on smoking cessation and NJOY on electronic cigarettes. JE Henningfield also owns an interest in intellectual property for a novel nicotine medication, an option for which has been sold to Niconovum USA. Through PinneyAssociates, Fant and Henningfield also provide consulting services to pharmaceutical companies on abuse potential assessment and the regulation of substances with a potential for abuse.


===2015 [https://pubmed.ncbi.nlm.nih.gov/25332459/ Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users]===  
===2015 [https://pubmed.ncbi.nlm.nih.gov/25332459/ Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users]===  
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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.
===2015 [https://pubmed.ncbi.nlm.nih.gov/25592454/ Explaining the effects of electronic cigarettes on craving for tobacco in recent quitters]===
*Conclusion: "From a public health perspective, there is a trade-off between e-cigarettes that provide high levels of nicotine, high satisfaction and more effects on craving for tobacco, but may also be addictive, and e-cigarettes that contain less nicotine and are less addictive, but are also less satisfactory and less efficient at relieving craving and at helping dependent smokers quit smoking. This trade-off must be kept in mind when regulating e-cigarettes."
**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...
='''Heated Tobacco Product (HTP)'''=
===2022 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424205/ An abuse liability assessment of the glo tobacco heating product in comparison to combustible cigarettes and nicotine replacement therapy]===
*"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'''=
='''Nicotine Pouches'''=
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='''Nicotine Replacement Therapy (NRT)'''=
='''Nicotine Replacement Therapy (NRT)'''=
===2022 [https://pubmed.ncbi.nlm.nih.gov/36543869/ Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum]===
*"These data reinforce previous research and provide the scientific evidence to support regulatory decisions demonstrating that Vuse Solo has an AL profile lower than that of combustible cigarettes but higher than that of nicotine gum and, therefore, may be a suitable replacement for cigarette smoking for some adult smokers."
**Citation: Campbell C, Jin T, Round EK, Schmidt E, Nelson P, Baxter S. Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum. Sci Rep. 2022 Dec 21;12(1):22080. doi: 10.1038/s41598-022-26417-2. PMID: 36543869; PMCID: PMC9772348.
***Acknowledgment: C.C., T.J., E.S., E.R., and S.B. are full-time employees of RAI Services Company, and P.N. is a former full-time employee of RAI Services Company. RAI Services Company is a wholly owned subsidiary of Reynolds American Inc., which is an indirect, wholly owned subsidiary of British American Tobacco plc.
===2022 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9424205/ An abuse liability assessment of the glo tobacco heating product in comparison to combustible cigarettes and nicotine replacement therapy]===
*"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.


===2020 [https://pubmed.ncbi.nlm.nih.gov/33176942/ Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers]===  
===2020 [https://pubmed.ncbi.nlm.nih.gov/33176942/ Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers]===  
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**Citation: Goldenson NI, Buchhalter AR, Augustson EM, Rubinstein ML, Henningfield JE. Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers. Drug Alcohol Depend. 2020 Dec 1;217:108395. doi: 10.1016/j.drugalcdep.2020.108395. Epub 2020 Nov 4. PMID: 33176942.
**Citation: Goldenson NI, Buchhalter AR, Augustson EM, Rubinstein ML, Henningfield JE. Abuse liability assessment of the JUUL system in four flavors relative to combustible cigarette, nicotine gum and a comparator electronic nicotine delivery system among adult smokers. Drug Alcohol Depend. 2020 Dec 1;217:108395. doi: 10.1016/j.drugalcdep.2020.108395. Epub 2020 Nov 4. PMID: 33176942.
***Acknowledgment: The study was funded by Juul Labs, Inc. NIG, EMA and MLR are full-time employees of Juul Labs, Inc., JEH and ARB are full-time employees of PinneyAssociates, Inc. PinneyAssociates provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc. Within the last two years, PinneyAssociates has consulted for British American Tobacco and Reynolds American Inc and subsidiaries on tobacco harm reduction. JEH co-holds a patent for a novel nicotine medication that has not been developed or commercialized. There are no other interests declared by authors.
***Acknowledgment: The study was funded by Juul Labs, Inc. NIG, EMA and MLR are full-time employees of Juul Labs, Inc., JEH and ARB are full-time employees of PinneyAssociates, Inc. PinneyAssociates provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc. Within the last two years, PinneyAssociates has consulted for British American Tobacco and Reynolds American Inc and subsidiaries on tobacco harm reduction. JEH co-holds a patent for a novel nicotine medication that has not been developed or commercialized. There are no other interests declared by authors.
===2020 [https://pubmed.ncbi.nlm.nih.gov/33250386/ Abuse liability assessment of the JUUL system in two nicotine concentrations compared to combustible cigarette, nicotine gum and comparator electronic nicotine delivery system]===
*Conclusions: These results suggest that the abuse liability of both 5.0 % and 3.0 % JS is: (1) substantially lower than UB cigarette; (2) somewhat lower than comparator ENDS; and (3) higher than nicotine gum. Additionally, the abuse liability of JS 5.0 % is somewhat higher than JS 3.0 %.
**Citation: Goldenson NI, Buchhalter AR, Augustson EM, Rubinstein ML, Van Hoof D, Henningfield JE. Abuse liability assessment of the JUUL system in two nicotine concentrations compared to combustible cigarette, nicotine gum and comparator electronic nicotine delivery system. Drug Alcohol Depend. 2020 Dec 1;217:108441. doi: 10.1016/j.drugalcdep.2020.108441. Epub 2020 Nov 24. PMID: 33250386.
***Acknowledgment: The study was funded by Juul Labs, Inc. NIG, EMA, DVH and MLR are full-time employees of Juul Labs, Inc., JEH and ARB are full-time employees of PinneyAssociates, Inc. PinneyAssociates provides consulting services on tobacco harm reduction on an exclusive basis to Juul Labs, Inc. Within the last two years, PinneyAssociates has consulted for British American Tobacco and Reynolds American Inc and subsidiaries on tobacco harm reduction. JEH co-holds a patent for a novel nicotine medication that has not been developed or commercialized. There are no other interests declared by authors.
===2019 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754311/ Abuse liability assessment of an electronic cigarette in combustible cigarette smokers]===
*"Collectively, the results of this study demonstrated that the ECIG device and liquids examined had moderate levels of abuse liability: on average lower than combustible cigarettes, but higher than an FDA-approved nicotine replacement therapy (i.e., nicotine inhaler)."
**Citation: Maloney SF, Breland A, Soule EK, Hiler M, Ramôa C, Lipato T, Eissenberg T. Abuse liability assessment of an electronic cigarette in combustible cigarette smokers. Exp Clin Psychopharmacol. 2019 Oct;27(5):443-454. doi: 10.1037/pha0000261. Epub 2019 Feb 18. PMID: 30777773; PMCID: PMC6754311.
***Acknowledgment: Funding; This study was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and U54DA036105 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. COI; Dr. Eissenberg is a paid consultant in litigation against the tobacco industry and is named on a patent for a device that measures the puffing behavior of ECIG users.


===2018 [https://pubmed.ncbi.nlm.nih.gov/29725702/ Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum]===  
===2018 [https://pubmed.ncbi.nlm.nih.gov/29725702/ Assessment of the abuse liability of three menthol Vuse Solo electronic cigarettes relative to combustible cigarettes and nicotine gum]===  
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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.
===2017 [https://pubmed.ncbi.nlm.nih.gov/28634710/ Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability]===
*"In summary, this study is the most robust assessment of the abuse liability of ECs published to date and uses approaches similar to those found in classic abuse liability studies of pharmaceutical products, including multiple instruments to measure the subjective effects of product use, as well as nicotine uptake. Under the set of study conditions described herein, use of the three Vuse Solo ECs tended to result in subjective measures responses and nicotine uptake that were between those measured with use of combustible cigarettes and nicotine gum. In general, the results are consistent with the conclusions of others that the abuse liability of ECs as a category is less than that of combustible cigarettes but greater than for nicotine gum, and likely other nicotine replacement products'
**Citation: Stiles MF, Campbell LR, Graff DW, Jones BA, Fant RV, Henningfield JE. Pharmacodynamic and pharmacokinetic assessment of electronic cigarettes, combustible cigarettes, and nicotine gum: implications for abuse liability. Psychopharmacology (Berl). 2017 Sep;234(17):2643-2655. doi: 10.1007/s00213-017-4665-y. Epub 2017 Jun 20. PMID: 28634710; PMCID: PMC5548902.
***Acknowledgment: Funding; This study was funded by RJ Reynolds Vapor Company through its affiliate RJ Reynolds Tobacco Company. COI; MF Stiles, LR Campbell, and BA Jones are full-time employees of RAI Services Company, which provides support across the Reynolds American Inc. operating companies. DW Graff is a full-time employee of Celerion and provided the original draft of this manuscript. RV Fant and JE Henningfield are full-time employees of PinneyAssociates, which provides consulting services on tobacco harm minimization (including nicotine replacement therapy and digital vapor products) to Niconovum USA, RJ Reynolds Vapor Company, and RAI Services Company (all subsidiaries of Reynolds American Inc.) In the past 3 years, PinneyAssociates has consulted to GlaxoSmithKline Consumer Healthcare on smoking cessation and NJOY on electronic cigarettes. JE Henningfield also owns an interest in intellectual property for a novel nicotine medication, an option for which has been sold to Niconovum USA. Through PinneyAssociates, Fant and Henningfield also provide consulting services to pharmaceutical companies on abuse potential assessment and the regulation of substances with a potential for abuse.


===2015 [https://pubmed.ncbi.nlm.nih.gov/25561385/ Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes]===  
===2015 [https://pubmed.ncbi.nlm.nih.gov/25561385/ Dependence levels in users of electronic cigarettes, nicotine gums and tobacco cigarettes]===  
*
*Conclusion: "Conclusions: Some e-cigarette users were dependent on nicotine-containing e-cigarettes, but these products were less addictive than tobacco cigarettes."
**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.


===2013 [https://www.federalregister.gov/documents/2013/04/02/2013-07528/modifications-to-labeling-of-nicotine-replacement-therapy-products-for-over-the-counter-human-use Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use]===  
===2013 [https://www.federalregister.gov/documents/2013/04/02/2013-07528/modifications-to-labeling-of-nicotine-replacement-therapy-products-for-over-the-counter-human-use Modifications To Labeling of Nicotine Replacement Therapy Products for Over-the-Counter Human Use]===  
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**Citation: Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacol Biochem Behav. 2002 Jun;72(3):559-68. doi: 10.1016/s0091-3057(02)00723-2. PMID: 12175452.
**Citation: Houtsmuller EJ, Fant RV, Eissenberg TE, Henningfield JE, Stitzer ML. Flavor improvement does not increase abuse liability of nicotine chewing gum. Pharmacol Biochem Behav. 2002 Jun;72(3):559-68. doi: 10.1016/s0091-3057(02)00723-2. PMID: 12175452.
***Acknowledgement: This study was supported by SmithKline Beecham Consumer Healthcare.
***Acknowledgement: This study was supported by SmithKline Beecham Consumer Healthcare.
===2000 [https://pubmed.ncbi.nlm.nih.gov/10823399/ A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler]===
*"We conclude that abuse liability from all four NRT products was low. Subjective dependence was moderate and did not differ across products. Behavioural dependence was modest and was positively related to rate of nicotine delivery."
**Citation: West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl). 2000 Apr;149(3):198-202. doi: 10.1007/s002130000382. PMID: 10823399.
***Acknowledgment: This study was funded by Pharmacia and Upjohn, Sweden.
===1997 [https://pubmed.ncbi.nlm.nih.gov/9160851/ Nicotine nasal spray and vapor inhaler: abuse liability assessment]===
*"Overall, results are consistent with the conclusion that the nicotine nasal spray and vapor inhaler are of substantially lower abuse liability than cigarettes in experienced cigarette smokers receiving initial exposure to these products."
**Citation: Schuh KJ, Schuh LM, Henningfield JE, Stitzer ML. Nicotine nasal spray and vapor inhaler: abuse liability assessment. Psychopharmacology (Berl). 1997 Apr;130(4):352-61. doi: 10.1007/s002130050250. PMID: 9160851.
***Acknowledgment: This work was supported by USPHS research grant DA03893 and training grant T32 DA07209 from the National Institute on Drug Abuse and conducted in collaboration with the NIDA Intramural Research Program Addiction Research Center. The authors thank Pharmacia Upjohn who kindly donated pharmaceutical supplies and conducted blood assays for this study.
='''Novel Oral Products (Chewable)'''=
===2021 [https://pubmed.ncbi.nlm.nih.gov/33502815/ Characterization of the Abuse Potential in Adult Smokers of a Novel Oral Tobacco Product Relative to Combustible Cigarettes and Nicotine Polacrilex Gum]===
*"The test products, under the conditions of this study, carry lower abuse potential than own-brand cigarettes and similar to nicotine polacrilex gum."
**Citation: Liu J, Wang J, Vansickel A, Edmiston J, Graff D, Sarkar M. Characterization of the Abuse Potential in Adult Smokers of a Novel Oral Tobacco Product Relative to Combustible Cigarettes and Nicotine Polacrilex Gum. Clin Pharmacol Drug Dev. 2021 Mar;10(3):241-250. doi: 10.1002/cpdd.909. Epub 2021 Jan 27. PMID: 33502815; PMCID: PMC7986766.
***Acknowledgment: J.L., J.W., A.V., J.E., and M.S. are employees of Altria Client Services LLC. D.G. was an employee of Celerion, Inc., who was contracted by Altria Client Services LLC to perform the study and analyze the study data.


='''VLNC - Very Low Nicotine Cigarettes'''=
='''VLNC - Very Low Nicotine Cigarettes'''=
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**Citation:
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***Acknowledgement:
='''Suggestions to add to this page'''=
===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]===