An electronic cigarette pod system delivering 6-methyl nicotine, a synthetic nicotine analog, marketed in the United States as "PMTA exempt".

As of April 14, 2022, the United States Food and Drug Administration (FDA) has been authorized to regulate tobacco products containing nicotine from any source, including synthetic, requiring manufacturers to submit a premarket tobacco product application (PMTA). A recent report by the World Health Organization (WHO) warned that non-nicotine tobacco alkaloids or other synthetic nicotine analogs could be used by manufacturers to bypass regulatory schemes focusing on nicotine alone. From October 2023 on, vape stores in the United States started selling a new electronic cigarette pod system, named Spree Bar, advertised as "PMTA exempt", with youth-appealing flavors and advertising. The products are marketed as containing "Metatine", a trademarked name for 6-methyl nicotine, a synthetic nicotine analog patented by a Chinese electronic cigarette manufacturer. Here we used liquid chromatography-mass spectrometry (LCMS) to confirm the presence of a chemical species with the molecular weight of 6-methyl nicotine in Spree Bar e-liquids. The FDA needs to determine whether, in its view, 6-methyl nicotine is a form of "nicotine" within the meaning of the Tobacco Control Act, or whether 6-methyl nicotine can be regulated as a drug under the Federal Food, Drug, and Cosmetic Act (FDCA).

Youth-appealing features in popular e-cigarette brand advertising in the USA after heightened scrutiny in 2018.

PURPOSE: Youth electronic cigarette (e-cigarette) use remains high in the USA, and advertising is a contributor. The purpose of this study was to identify themes and characteristics of popular e-cigarette companies' advertising after e-cigarette companies became more highly scrutinised in 2018. METHODS: Using a systematic, quantitative content analysis, three trained coders coded e-cigarette advertisements from JUUL, Puff Bar, Vuse and Blu from 2019 and 2020. Based on previous work, they coded for: type of advertisement, flavours, promotions, product cues, descriptors, claims, imagery, youth-oriented themes and sensational appeals. RESULTS: Of the 401 e-cigarette advertisements, the majority were emails (38.2%) and Instagram posts (30.9%). Over half (53.6%) showed flavours other than tobacco, with Puff Bar leading the brands (70.2%; p<0.001). The most frequently used product cues were showing the product (51.4%) or packaging (42.4%). The most common claim was being an alternative to smoking (14.2%). The most frequently used imagery was fruit (14.0%), employed most by Puff Bar (p<0.001). The only youth-oriented theme present was humour (4.2%). Positive sensations (eg, good taste, good smell or satisfying; 17.1%) was the most common form of appeal, with Puff Bar using it at the highest frequency (p<0.001). CONCLUSION: Even with heightened scrutiny of e-cigarette brands, advertisements still included youth-appealing content such as flavours, fruit imagery and positive sensations. Puff Bar led in all these categories, and it rapidly gained market share after market leader JUUL limited the sales of its flavoured products. Research should continue to monitor the characteristics of e-cigarette advertisements and consider their impact on youth.

Juul and the upsurge of e-cigarette use among college undergraduates.

OBJECTIVE: Examine trends in e-cigarette use, and Juul use specifically, among U.S. college students. PARTICIPANTS: In 2016, we established a cohort of 529 incoming first-year students to a large Midwestern University. In 2018, these students (now third-years) were re-contacted, and a new sample of 611 incoming first-year students was enrolled. METHODS: First-year students in 2016 completed a survey assessing their e-cigarette use; in 2018, first- and second-year students reported on e-cigarette use, and use of Juul specifically. RESULTS: From 2016 to 2018, past 30-day e-cigarette use rose from 5.9% to 27.7%. In 2018, for Juul alone, ever use was above 35% and past 30-day use was above 20% for both cohorts. Juul use did not differ by gender, but was associated with higher socioeconomic status (SES) and being White. CONCLUSIONS: Findings present disturbing possibilities for long-term nicotine addiction among the next generation, and underscore the need for a rapid public health response.

E-Cigarettes and the Multiple Responsibilities of the FDA.

This paper considers the responsibilities of the FDA with regard to disseminating information about the benefits and harms of e-cigarettes. Tobacco harm reduction advocates claim that the FDA has been overcautious and has violated ethical obligations by failing to clearly communicate to the public that e-cigarettes are far less harmful than cigarettes. We argue, by contrast, that the FDA's obligations in this arena are more complex than they may appear at first blush. Though the FDA is accountable for informing the public about the health risks and benefits of products it regulates, it also has other roles (and attendant responsibilities) that inform when and how it should disseminate information. In addition to being a knowledge purveyor, it is also a knowledge producer, an advisor to the public, and a practical agent shaping the material conditions in which people make health-related choices. In our view, those other roles call for caution in the way the FDA interprets and communicates the available evidence.

Testing potential disclosures for e-cigarette sponsorship on social media.

OBJECTIVES: Few e-cigarette social media posts are authentic posts to friends; most come from commercially sponsored influencers. Potential disclosure strategies need to be tested to confirm whether users recognize such posts as commercially sponsored. METHODS: Between July - August 2019, young adult (ages 16-24; n = 200) participants were recruited to view their native Instagram feed on a laboratory mobile device. Posts from e-cigarette influencers were manipulated to add either #ad or #sponsored while eye tracking software measured visual attention. Participants self-reported their interpretation of the hashtags in open-ended responses. Logistic regression analyses compared recognition of commercial content by condition, and qualitative content analyses summarized the key themes related to the hashtags. RESULTS: The #ad condition had nearly twice the odds of commercial recognition compared to #sponsored (OR = 1.98, CI: 1.14-3.38). Every second of attention paid to the hashtag significantly increased the odds of commercial recognition by 22% (OR: 1.22, CI: 1.00-1.33). CONCLUSION: The #ad disclosure attracted visual attention and significantly increased recognition of commercial sponsorship from young social media users. Labeling commercially sponsored content on social media is a promising strategy to better inform users about paid social media influence.

Beyond Strong Enforcement: Understanding the Factors Related to Retailer Compliance With Tobacco 21.

INTRODUCTION: Tobacco 21 (T21), which sets the minimum legal sales age for tobacco to age 21, is now a national law in the United States. Although T21 is expected to help curb youth tobacco use, its impact may be dampened due to poor retailer compliance. Even within environments where enforcement is strong (ie, compliance checks are conducted with tough sanctions for violations), compliance might vary due to other factors. AIMS AND METHODS: Three studies were conducted in Columbus, OH, where T21 became strongly enforced in 2018. These studies examined how retailer compliance related to features of the neighborhood in which a retailer was located (Study 1), features of the retailer (Study 2), and features of the retail cashier (Study 3). RESULTS: Study 1 found that, after controlling for race- and age-based factors, retailers located in high (vs. low)-poverty neighborhoods had a lower likelihood of conducting identification (ID) checks. Study 2 found that ID checks were related to whether retailers displayed signage about T21, as required by the city law. Study 3 found that, among cashiers, T21 awareness (which was high) and perceptions about T21 (which were moderate) were not generally related to their retailer's compliance; having (vs. not having) scanners for ID checks was related to a higher likelihood of compliance. CONCLUSIONS: These studies emphasize the many, multilevel factors influencing T21 outcomes. Findings also indicate the potential for T21 to widen disparities in tobacco use, indicating the need for strategies to equitably improve T21 compliance. IMPLICATIONS: T21, which sets the minimum legal sales age for all tobacco products to age 21, is now a national law in the United States. Despite optimistic projections about what T21 could achieve, the ultimate impact may be dampened when it is applied in real-world settings. Our project revealed the many, multilevel factors influencing T21 compliance. Findings also indicate the potential for T21 to widen disparities in tobacco use if gaps in compliance persist. Strategies for equitably improving T21 compliance are discussed. This article is of relevance to areas interested in implementing or improving their local T21 enforcement.

Impact of Cigarette Filter Ventilation on U.S. Smokers' Perceptions and Biomarkers of Exposure and Potential Harm.

BACKGROUND: Relationships between cigarette filter ventilation levels, biomarkers of exposure (BOE) and potential harm (BOPH), and harm perceptions were examined. METHODS: Filter ventilation levels in cigarette brands were merged with Wave 1 (2013-2014) Population Assessment of Tobacco Use and Health study. Data were restricted to smokers who reported a usual brand and not regular users of other tobacco products. BOEs included nicotine, tobacco-specific nitrosamines, volatile organic compounds (VOC), and polycyclic aromatic hydrocarbons. BOPHs measured inflammation and oxidative stress. Perceived harm was assessed as self-reported risk of one's usual brand compared with other brands. RESULTS: Filter ventilation ranged from 0.2% to 61.1% (n = 1,503). Adjusted relationships between filter ventilation and BOE or BOPH were nonsignificant except for VOC N-acetyl-S-(phenyl)-L-cysteine (PHMA) and high-sensitivity C-reactive protein (hsCRP). In pairwise comparisons, PHMA was higher in quartile (Q) 4 (4.23 vs. 3.36 pmol/mg; P = 0.0103) and Q3 (4.48 vs. 3.36 pmol/mg; P = 0.0038) versus Q1 of filter ventilation and hsCRP comparisons were nonsignificant. Adjusted odds of perceiving one's own brand as less harmful was 26.87 (95% confidence interval: 4.31-167.66), 12.55 (3.01-52.32), and 19.18 (3.87-95.02) times higher in the Q2, Q3, and Q4 of filter ventilation compared with Q1 (P = 0.0037). CONCLUSIONS: Filter ventilation was not associated with BOE or BOPH, yet smokers of higher ventilated cigarettes perceived their brand as less harmful than other brands compared with smokers of lower ventilated cigarettes. IMPACT: Research to understand the impact of this misperception is needed, and remedial strategies, potentially including a ban on filter ventilation, are recommended.

Electronic cigarette use and risk of cigarette and smokeless tobacco initiation among adolescent boys: A propensity score matched analysis.

INTRODUCTION: Electronic cigarette (e-cigarette) use among adolescents is associated with increased risk of subsequent cigarette smoking initiation in observational research. However, the existing research was not designed to answer causal questions about whether adolescent e-cigarette users would have initiated cigarette smoking if they had never used e-cigarettes. The current study used a causal inference framework to identify whether male adolescent e-cigarette users were at increased risk of initiating cigarette smoking and smokeless tobacco (SLT) use, compared to similar boys who had never used e-cigarettes. METHODS: Boys from urban and Appalachian Ohio (N = 1220; ages 11-16 years at enrollment) reported use of e-cigarettes, cigarettes, and SLT at baseline and every six months for two years. A propensity score matching design was implemented, matching one e-cigarette user to two similar e-cigarette non-users. This analysis was completed in 25 multiple imputed datasets to account for missing data. Risk ratios (RRs) comparing risk of initiating cigarettes and SLT for e-cigarette users and nonusers were estimated. RESULTS: Compared to non-users, e-cigarette users were more than twice as likely to later initiate both cigarette smoking (RR = 2.71; 95% CI: 1.89, 3.87) and SLT (RR = 2.42; 95% CI: 1.73, 3.38). They were also more likely to become current (i.e., past 30-day) cigarette smokers (RR = 2.20; 95% CI: 1.33, 3.64) and SLT users (RR = 1.64; 95% CI: 1.01, 2.64). CONCLUSIONS: Adolescent boys who used e-cigarettes had increased risk of later initiating traditional tobacco products when compared to similar boys who had never used e-cigarettes.

Adverse effects of electronic cigarettes on the disease-naive oral microbiome.

Six percent of Americans, including 3 million high schoolers, use e-cigarettes, which contain potentially toxic substances, volatile organic compounds, and metals. We present the first human study on the effects of e-cigarette exposure in the oral cavity. By interrogating both immunoinflammatory responses and microbial functional dynamics, we discovered pathogen overrepresentation, higher virulence signatures, and a brisk proinflammatory signal in clinically healthy e-cigarette users, equivalent to patients with severe periodontitis. Using RNA sequencing and confocal and electron microscopy to validate these findings, we demonstrate that the carbon-rich glycol/glycerol vehicle is an important catalyst in transforming biofilm architecture within 24 hours of exposure. Last, a machine-learning classifier trained on the metagenomic signatures of e-cigarettes identified as e-cigarette users both those individuals who used e-cigarettes to quit smoking, and those who use both e-cigarettes and cigarettes. The present study questions the safety of e-cigarettes and the harm reduction narrative promoted by advertising campaigns.

Nicotine Reduction in Cigarettes: Literature Review and Gap Analysis.

BACKGROUND: The US Food and Drug Administration (FDA) is considering reducing nicotine levels in cigarettes to "minimally or non-addictive levels." However, important research gaps remain, and the FDA must determine when the available research is sufficient to support moving forward. METHODS: The authors conducted a systematic review of research articles in PubMed relating to nicotine reduction. Building on a review of risk assessment best practices, the authors also developed a risk assessment framework for tobacco regulation and used it to guide a gap analysis of nicotine reduction research. RESULTS: The final sample consisted of 78 articles. The majority examined either nicotine dependence on very low nicotine cigarettes (VLNCs) or markers of potential health effects of using VLNCs. One-third of the identified articles reported results from four large randomized controlled trials (RCTs). While these studies report promising results and suggest that a nicotine reduction rule would be a powerful tool to reduce cigarette smoking, our gap analysis suggests that there is a need for studies that better reflect the use and availability of a wide range of tobacco/nicotine products and the potential for dual- or multi-product use. CONCLUSION: The current body of research on nicotine reduction is weighted towards RCTs, which is appropriate for a policy that has not yet been implemented anywhere in the world. The FDA must consider a wide range of factors that may impact a product standard's public health impact, including those difficult to assess in RCTs, such as a nicotine reduction rule's impact on smoking initiation and relapse. IMPLICATIONS: This systematic review presents a gap analysis based on a risk assessment framework to help identify remaining research priorities to inform FDA's potential product standard to reduce nicotine levels in cigarettes. Quickly addressing those gaps would support the FDA's effort to develop a nicotine reduction product standard that will be effective and withstand legal challenges.

Risk Assessment for Tobacco Regulation.

Risk assessment is a process that uses a transparent, reproducible and pre-established methodology to evaluate alternatives for managing health-related risks. Although an array of federal agencies regularly use risk assessment to inform regulatory decisions, its application to tobacco regulation is new. By comparing examples of FDA risk assessments for food and tobacco, this paper highlights some of the challenges inherent in applying risk assessment methodologies to tobacco regulation. In doing so, it calls upon researchers to work with the FDA to develop a tobacco-specific approach to risk assessment that reflects the Tobacco Control Act's regulatory framework and the distinctive features of tobacco products and tobacco use.