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      Flavors Enhance Nicotine Vapor Self-administration in Male Mice

      research-article
      , BS, , BS, , PhD
      Nicotine & Tobacco Research
      Oxford University Press

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          Abstract

          Introduction

          Although the use of combustible cigarettes has decreased in many urban regions of America, the use of electronic nicotine delivery systems (ENDS) has dramatically increased. ENDS, or electronic cigarettes (e-cigarettes), differ from combustible cigarettes given that there are no restrictions on flavorant additives in e-liquids. With 95% of ENDS users vaping flavored e-liquids, it is critical to understand how flavors alter vaping-related behaviors. We have previously shown that menthol and green apple flavors enhance nicotine reward-related behavior in a mouse model and in the present study have investigated how menthol and green apple flavors alter e-Vape self-administration behavior in male mice.

          Methods

          Adult C57/BL6J male mice were used in vapor-inhalation self-administration assays. Mice were assigned vaping e-liquids (6 mg/mL nicotine with or without menthol or green apple flavor) to escalate on a fixed-ratio 1 (FR1) schedule in daily 3-hour sessions to examine initiation-related behaviors. Following escalation, mice were transitioned to a FR3 and progressive ratio schedules in 3-hour sessions to examine reinforcement-related behaviors.

          Results

          Here we observed that male mice exhibited increased rates of self-administration escalation on a FR1 schedule when assigned to flavored e-liquids. Upon transition to FR3, mice continued to exhibit enhanced levels of reinforcement with flavored e-liquids. We also observed that mice self-administer zero-nicotine green apple flavored e-liquids.

          Conclusions

          These data provide additional evidence that ENDS flavors enhance vaping-related initiation and reinforcement-related behavior and promote the need to continue investigating the role ENDS flavors play in vaping-related behaviors.

          Implications

          There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our study here shows that flavors significantly enhance the acquisition and reinforcement of vaping-related behavior. This suggests that flavors in electronic nicotine delivery systems significantly increase the risk of addiction-related behaviors among users of vaping products.

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          Most cited references28

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          Notes from the Field: Use of Electronic Cigarettes and Any Tobacco Product Among Middle and High School Students — United States, 2011–2018

          Electronic cigarettes (e-cigarettes) are battery-powered devices that provide nicotine and other additives to the user in the form of an aerosol ( 1 ). E-cigarettes entered the U.S. marketplace in 2007 ( 1 ), and by 2014, e-cigarettes were the most commonly used tobacco product among U.S. youths ( 2 ). Data from the 2011–2018 National Youth Tobacco Survey (NYTS), a cross-sectional, voluntary, school-based, self-administered, pencil-and-paper survey of U.S. middle and high school students, were analyzed to determine the prevalence of current use (≥1 day in past 30 days) of e-cigarettes,* current use of any tobacco product, † frequency of (number of days during the preceding 30 days) e-cigarette use, and current use (any time during preceding 30 days) of any flavored e-cigarettes among U.S. middle school (grades 6–8) and high school (grades 9–12) students. Logistic regression (2011–2018) and t-tests (2017–2018) were performed to determine statistically significant differences (p 0.05) (Figure). Current use of any tobacco product among middle school students was 7.5% (870,000 students) in 2011 and 7.2% (840,000 students) in 2018 (p>0.05). During 2017–2018, overall tobacco product use increased by 38% among high school students (from 19.6% to 27.1%, p<0.001) and by 29% among middle school students (from 5.6% to 7.2%, p = 0.008). Current e-cigarette use increased considerably among U.S. middle and high school students during 2017–2018, reversing a decline observed in recent years and increasing overall tobacco product use ( 3 ). Moreover, during 2017–2018, frequent e-cigarette use increased among high school students. Although e-cigarettes have the potential to benefit adult smokers if used as a complete substitute for combustible tobacco smoking, the use of any form of tobacco product among youths, including e-cigarettes, is unsafe ( 1 ). The Surgeon General has concluded that e-cigarette use among youths and young adults is of public health concern; exposure to nicotine during adolescence can cause addiction and can harm the developing adolescent brain ( 1 ). The rise in e-cigarette use during 2017–2018 is likely because of the recent popularity of e-cigarettes shaped like a USB flash drive, such as JUUL; these products can be used discreetly, have a high nicotine content, and come in flavors that appeal to youths ( 4 ). In September 2018, the Food and Drug Administration (FDA) issued more than 1,300 warning letters and civil money penalty fines to retailers who illegally sold e-cigarette products to minors, the majority of which were blu, JUUL, Logic, MarkTen XL, and Vuse; this was the largest coordinated enforcement effort in FDA’s history ( 5 ). Sustained implementation of proven population-based strategies, in coordination with the regulation of tobacco products by FDA, is key to reducing all forms of tobacco product use and initiation, including e-cigarettes, among U.S. youths ( 1 ).
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            Vaping versus JUULing: how the extraordinary growth and marketing of JUUL transformed the US retail e-cigarette market

            Background While national surveys showed declines in e-cigarette use in the USA between 2015 and 2016, recent reports indicate that JUUL, a sleekly designed e-cigarette that looks like a USB drive, is increasingly being used by youth and young adults. However, the extent of JUUL’s growth and its marketing strategy have not been systematically examined. Methods A variety of data sources were used to examine JUUL retail sales in the USA and its marketing and promotion. Retail store scanner data were used to capture the retail sales of JUUL and other major e-cigarette brands for the period 2011–2017. A list of JUUL-related keywords was used to identify JUUL-related tweets on Twitter; to identify JUUL-related posts, hashtags and accounts on Instagram and to identify JUUL-related videos on YouTube. Results In the short 3-year period 2015–2017, JUUL has transformed from a little-known brand with minimum sales into the largest retail e-cigarette brand in the USA, lifting sales of the entire e-cigarette category. Its US$150 million retail sales in the last quarter of 2017 accounted for about 40% of e-cigarette retail market share. While marketing expenditures for JUUL were moderate, the sales growth of JUUL was accompanied by a variety of innovative, engaging and wide-reaching campaigns on Twitter, Instagram and YouTube, conducted by JUUL and its affiliated marketers. Conclusions The discrepancies between e-cigarette sales data and the prevalence of e-cigarette use from surveys highlight the challenges in tracking and understanding the use of new and emerging tobacco products. In a rapidly changing media environment, where successful and influential marketing campaigns can be conducted on social media at little cost, marketing expenditures alone may not fully capture the influence, reach and engagement of tobacco marketing.
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              Four hundred and sixty brands of e-cigarettes and counting: implications for product regulation

              Introduction E-cigarettes are largely unregulated and internet sales are substantial. This study examines how the online market for e-cigarettes has changed over time: in product design and in marketing messages appearing on websites. Methods Comprehensive internet searches of English-language websites from May–August 2012 and December 2013–January 2014 identified brands, models, flavours, nicotine strengths, ingredients and product claims. Brands were divided into older and newer groups (by the two searches) for comparison. Results By January 2014 there were 466 brands (each with its own website) and 7764 unique flavours. In the 17 months between the searches, there was a net increase of 10.5 brands and 242 new flavours per month. Older brands were more likely than newer brands to offer cigalikes (86.9% vs 52.1%, p<0.01), and newer brands more likely to offer the more versatile eGos and mods (75.3% vs 57.8%, p<0.01). Older brands were significantly more likely to claim that they were healthier and cheaper than cigarettes, were good substitutes where smoking was banned and were effective smoking cessation aids. Newer brands offered more flavours per brand (49 vs 32, p<0.01) and were less likely to compare themselves with conventional cigarettes. Conclusions The number of e-cigarette brands is large and has been increasing. Older brands tend to highlight their advantages over conventional cigarettes while newer brands emphasise consumer choice in multiple flavours and product versatility. These results can serve as a benchmark for future research on the impact of upcoming regulations on product design and advertising messages of e-cigarettes.
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                Author and article information

                Journal
                Nicotine Tob Res
                Nicotine Tob Res
                nictob
                Nicotine & Tobacco Research
                Oxford University Press (US )
                1462-2203
                1469-994X
                March 2021
                29 August 2020
                29 August 2020
                : 23
                : 3
                : 566-572
                Affiliations
                Department of Biomedical Sciences, Joan C Edwards School of Medicine at Marshall University , Huntington, WV
                Author notes
                Corresponding Author: Brandon J. Henderson, PhD, Department of Biomedical Sciences, Joan C Edwards School of Medicine at Marshall University, 1700 3rd Avenue, 410 BBSC, Huntington, WV 25703, USA. Telephone: 304-696-7316, Fax: 304-696-7391; E-mail: hendersonbr@ 123456marshall.edu
                Author information
                http://orcid.org/0000-0003-0381-028X
                Article
                ntaa165
                10.1093/ntr/ntaa165
                7885783
                32860507
                f18a2496-5906-462a-a0c5-73ca34fe8166
                © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 24 October 2019
                : 14 August 2020
                : 24 August 2020
                : 18 September 2020
                Page count
                Pages: 7
                Funding
                Funded by: National Institute on Drug Abuse, DOI 10.13039/100000026;
                Award ID: DA040047
                Funded by: FDA Center for Tobacco Products;
                Award ID: DA046335
                Funded by: PhRMA Foundation, DOI 10.13039/100001797;
                Categories
                Original Investigations
                AcademicSubjects/MED00010
                AcademicSubjects/SOC02541

                Agriculture
                Agriculture

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