Can alternative nicotine products put the final nail in the smoking coffin?

This review describes the evolution of smoking prevalence in countries with relatively high adoption of alternative nicotine products such as e-cigarettes, heated tobacco, and snus compared to neighboring countries where these products are less prevalent. The data indicate that countries with high adoption of alternative nicotine products have been able to achieve lower smoking rates. The findings suggest that adoption of alternative nicotine products may help in reduce smoking prevalence faster than traditional tobacco control measures solely focused on prevention and cessation.

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool?

Nicotine pouches to be put under the upper lip are a new category of products that are being rapidly developed and marketed as consumer goods with little research or regulatory oversight. We have identified research gaps in assessing their harm and benefit potential, and possible regulatory science approaches to inform the policies that can allow a maximization of the category's public health potential while minimizing unintended consequences. Implications: This commentary presents a potential blueprint for a comprehensive assessment of the nicotine pouches category. Data from the proposed research areas can better inform the regulatory policy decisions around the category, with the aim to maximize the category's tobacco harm reduction potential while minimizing unintended harms.

Closing Perspective on the Special Issue on JUUL.

Objective: This article provides an overview of this theme issue of the American Journal of Health Behavior dedicated to electronic nicotine delivery systems (ENDS), with a special focus on JUUL. Methods: The author summarizes key findings from included papers and offers an evaluative perspective on ENDS as tools for smoking cessation versus the prospect of their appeal to previous non-smokers. Results: Delineation of certain metrics (eg, defining who is a smoker) and clarification about an acceptable level of unintended consequences weighed against harm reduction confound conclusions about the public health role of ENDS/JUUL. Conclusion: Until agreement on key definitions and performance of well-controlled studies, a system that promotes ENDS/JUUL use among smokers but discourages their use by never-smokers is a regulatory challenge.

Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff.

INTRODUCTION: The single-dose pharmacokinetics (PK) of a novel, non-tobacco-based nicotine pouch, ZYN, 3 and 6 mg, were compared with 8 mg General snus (part 1) and ZYN 8 mg was compared with 18 mg Longhorn moist snuff (part 2). The present study demonstrates the characteristics of three strengths of a novel tobacco-free oral snus, ZYN, viz. the extraction of nicotine from the oral cavity and its uptake into the systemic blood circulation. Comparison is made to Swedish General snus and American Longhorn moist snuff and from literature 4 mg Nicorette gum and mean of 13 brands of e-cigarettes. AIMS AND METHODS: A single-dose randomized crossover design was used. In vivo extraction and PK parameters were determined. RESULTS: Part 1. The AUCinf of ZYN 3 mg was 27% smaller than that of 8 mg General and the AUCinf of ZYN 6 mg was 34% larger than that of 8 mg General. Less nicotine was extracted from ZYN 3 mg (1.5 mg) and more from ZYN 6 mg (3.5 mg) than from 8 mg General (2.4 mg). The extracted fractions of nicotine for both ZYN products (56% and 59%) were significantly larger than for 8 mg General (32%). RESULTS: Part 2. Close to identical plasma nicotine curves, AUCinf and Cmax were found for ZYN 8 mg and Longhorn Natural 18 mg moist snuff. The extracted amount of nicotine from ZYN 8 mg (3.8 mg) was larger than the amount extracted from Longhorn Natural 18 mg (3.0 mg), but smaller than the extracted amount of nicotine from General 2 × 8 mg snus pouches (5.0 mg). The extracted fraction of nicotine for ZYN 8 mg (50%) was larger than for Longhorn Natural (19%) and General 2 × 8 mg snus pouches (33%). CONCLUSIONS: The two higher doses of ZYN (6 and 8 mg) deliver nicotine as quickly and to a similar extent as existing smokeless products, with no significant adverse effects.

Initial Information on a Novel Nicotine Product.

BACKGROUND AND OBJECTIVES: This is the first study to assess the appeal and interest among adults in a new consumer tobacco product, ZYN. We also describe ZYN users, patterns of use, and reasons for use. METHODS: Two data sets, consisting of a ZYN-naive consumer panel (n = 5179) and ZYN users (n = 1266), were provided by Swedish Match North America. Descriptive, cross-sectional analyses and logistic regression assessed the perceptions of and likelihood of buying ZYN in the consumer panel and the characteristics of ZYN users. RESULTS: The majority of current smokeless tobacco (ST) users in the consumer panel found that ZYN was moderately-extremely appealing, while never and former tobacco users indicated much less interest; the former were more likely to buy ZYN than other groups. The highest percentage of ZYN users were former tobacco users (43%); very few were never users (4%). The most popular reason for using ZYN was "Less harmful to my health than other tobacco products," followed by "ease of use." DISCUSSION AND CONCLUSIONS: Nonusers of tobacco had very little interest in ZYN. ST users are not only more interested and likely to buy ZYN than other tobacco users, they were the largest group of regular users. SCIENTIFIC SIGNIFICANCE: The first assessment of a new nicotine product, ZYN, suggests that current and former tobacco users may perceive ZYN as a reduced-risk product. ZYN potentially could be used as a smoking/tobacco-cessation aid based on reasons of current users. (Am J Addict 2020;00:00-00).

Varenicline: mode of action, efficacy, safety and accumulated experience salient for clinical populations.

Objective: Varenicline, a selective partial agonist of the α4ß2 nicotinic acetylcholine receptor, is a smoking cessation pharmacotherapy that more than doubles the chance of quitting smoking at 6 months compared with placebo. This article reviews salient knowledge of the discovery, pharmacological characteristics, and the efficacy and safety of varenicline in general and in specific populations of smokers and provides recommendations to support use in clinical practice.Methods: Literature searches for varenicline were conducted using PubMed, with date limitations of 2000-2018 inclusive, using search terms covering the discovery, mechanism of action, pharmacokinetics, efficacy and safety in different populations of smokers, alternative quit approaches and combination therapy. Selection of safety and efficacy data was limited to clinical trials, meta-analyses and observational studies.Results: Standard administration of varenicline is efficacious in helping smokers to quit, including smokers with cardiovascular disease and chronic obstructive pulmonary disease. Furthermore, varenicline efficacy may be improved with pre-loading, a gradual quitting approach for smokers unwilling or unable to quit abruptly, and extended treatment in smokers who have recently quit to help maintain abstinence. Initial concerns regarding the association of varenicline with increased risk of neuropsychiatric and cardiovascular adverse events have been disproven after extensive clinical evaluations, and the benefit-risk profile of varenicline is considered favorable.Conclusions: Varenicline is efficacious and safe for all adult smokers with a range of clinical characteristics. Evidence suggests that approaches offering greater flexibility in timing and duration of treatment may further extend treatment efficacy and clinical reach.

A Comparison of Dependence across Different Types of Nicotine Containing Products and Coffee.

INTRODUCTION: Few studies have compared the dependence to different tobacco and nicotine products. Even less is known about how it relates to dependence on other common drugs, e.g., caffeine. In this study degree of dependence was compared between snus, cigarettes, nicotine replacement (NR), electronic cigarettes and coffee. METHODS: A random sample of Swedish citizens belonging to an internet panel were contacted from September to October 2017. The responders were asked among other related things about their use of snus, NR, traditional cigarette or e-cigarette use and coffee consumption. The indicators of dependence used were: (A) the Heavy Smoking Index, (B) The proportions that used within 30 min after raising in the morning, (C) rating the first use in the morning as the most important and (D) Stating that it would be very hard to give up entirely. RESULTS: Significantly fewer coffee drinkers started use within 30 min of awakening compared with all other products. The first use of the day was found to be more important for snus users compared with other products. On HSI there was no difference between snus and cigarettes. Snus and cigarettes were rated as being more difficult to give up than NR and coffee. CONCLUSION: Dependence to traditional cigarettes and snus seem to be relatively similar while NR was rated lower and coffee lowest. Since the prevalence of caffeine use in all forms is so much more prevalent than nicotine there might be more persons in the society heavily dependent on caffeine. IMPLICATION: Tobacco products are likely more dependence forming than NR products and coffee although there might be more people dependent on caffeine. The addiction to coffee or caffeine is seldom discussed in the society probably because of the little or no harm it causes. FUNDING: The Snus Commission in Sweden (snuskommissionen) funded the data collection. No funding used for the analysis and writing of manuscript.

Item Response Theory analysis of Fagerström Test for Cigarette Dependence.

INTRODUCTION: The Fagerström Test for Cigarette Dependence (FTCD) and the Heaviness of Smoking Index (HSI) are the gold standard measures to assess cigarette dependence. However, FTCD reliability and factor structure have been questioned and HSI psychometric properties are in need of further investigations. The present study examined the psychometrics properties of the FTCD and the HSI via the Item Response Theory. METHODS: The study was a secondary analysis of data collected in 862 Italian daily smokers. Confirmatory factor analysis was run to evaluate the dimensionality of FTCD. A Grade Response Model was applied to FTCD and HSI to verify the fit to the data. Both item and test functioning were analyzed and item statistics, Test Information Function, and scale reliabilities were calculated. Mokken Scale Analysis was applied to estimate homogeneity and Loevinger's coefficients were calculated. RESULTS: The FTCD showed unidimensionality and homogeneity for most of the items and for the total score. It also showed high sensitivity and good reliability from medium to high levels of cigarette dependence, although problems related to some items (i.e., items 3 and 5) were evident. HSI had good homogeneity, adequate item functioning, and high reliability from medium to high levels of cigarette dependence. Significant Differential Item Functioning was found for items 1, 4, 5 of the FTCD and for both items of HSI. CONCLUSIONS: HSI seems highly recommended in clinical settings addressed to heavy smokers while FTCD would be better used in smokers with a level of cigarette dependence ranging between low and high.

Associations of Proposed Relative-Risk Warning Labels for Snus With Perceptions and Behavioral Intentions Among Tobacco Users and Nonusers.

INTRODUCTION: The US Food and Drug Administration can require changes in warning statements for modified risk tobacco products. We report an independent analysis of a consumer perception survey sponsored by Swedish Match as part of a Modified Risk Tobacco Product application to change warning labels for Swedish snus products. METHODS: The survey exposed each of 4324 daily exclusive cigarette smokers, 1033 daily smokeless tobacco users, 1205 daily other tobacco users, 726 former users, and 5915 triers/never users to one of four current warnings and two proposed relative-risk labels (No tobacco product is safe, but this product presents lower risks to health than cigarettes, or No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes) for snus. Descriptive and logistic regression analyses examined four outcomes: believability, harmfulness, motivation to use, and intention to buy snus. RESULTS: Compared with the current not-safe-alternative warning, adult tobacco users who viewed the proposed labels perceived them as less believable, perceived snus as less harmful and were more likely to use and buy snus. The proposed labels had no impact on former smokers' likelihood to use and buy snus; triers/never users viewing the substantially lower risk label were more likely to buy snus. CONCLUSIONS: Tobacco users viewing the proposed labels perceived snus as less harmful than cigarettes and may be more likely to use and buy snus. If labeling changes lead to increased snus use and cigarette reduction or abstinence, public health may benefit. If the opposite occurs, public health could suffer.

Time to First Use Among Daily Smokers and Smokeless Tobacco Users.

INTRODUCTION: Time to the first cigarette after waking up in the morning is the most validated measure of dependence among smokers, and its complement is also a good indicator of dependence for smokeless tobacco (ST) users. However, no studies have directly compared these measures. METHODS: We used a multivariate logistic regression model to compare the time to first use (TTFU) of cigarettes and ST among white men 18+ years of age who were daily users in the 2003 Tobacco Use Supplement of the Current Population Survey. Smokers were classified as light (1-14 cigarettes per day [cpd]), moderate (15-24 cpd), and heavy (25+ cpd) and ST users were classified as former smokers or exclusive users. RESULTS: There was no difference in TTFU within 5min between light smokers and exclusive ST users (Odds ratio [OR] = 1.3, CI = 0.95-1.7), but the latter were less likely to use tobacco within 30min (OR = 0.75, CI = 0.62-0.89). ST former smokers were more likely than light smokers to have a TTFU within 5min (OR = 1.5, CI = 1.1-2.0) but not within 30min. Moderate and heavy smokers had significantly higher odds of TTFU within both time points than light smokers. CONCLUSION: Compared to light smokers, the likelihood of TTFU within 5min was similar among exclusive ST users and was slightly higher among ST former smokers, offering some support for the Fagerström-Eissenberg hypothesis that the dependence level of cigarettes is higher than that of ST.

Estimating the harms of nicotine-containing products using the MCDA approach.

BACKGROUND: An international expert panel convened by the Independent Scientific Committee on Drugs developed a multi-criteria decision analysis model of the relative importance of different types of harm related to the use of nicotine-containing products. METHOD: The group defined 12 products and 14 harm criteria. Seven criteria represented harms to the user, and the other seven indicated harms to others. The group scored all the products on each criterion for their average harm worldwide using a scale with 100 defined as the most harmful product on a given criterion, and a score of zero defined as no harm. The group also assessed relative weights for all the criteria to indicate their relative importance. FINDINGS: Weighted averages of the scores provided a single, overall score for each product. Cigarettes (overall weighted score of 100) emerged as the most harmful product, with small cigars in second place (overall weighted score of 64). After a substantial gap to the third-place product, pipes (scoring 21), all remaining products scored 15 points or less. INTERPRETATION: Cigarettes are the nicotine product causing by far the most harm to users and others in the world today. Attempts to switch to non-combusted sources of nicotine should be encouraged as the harms from these products are much lower.

Predictors of success for smoking cessation at the workplace: a longitudinal study.

BACKGROUND: The effectiveness of worksite interventions to reduce smoking is debatable. OBJECTIVES: A comprehensive smoking cessation intervention was implemented in a community of more than 17,000 employees at three different health care companies. The primary endpoint was abstinence at 24 months (self-reported and confirmed by exhaled carbon monoxide ≤ 6 parts per million). Predictors of long-term abstinence were analysed by multivariable regression analysis. METHODS: The study was designed as an investigator-initiated and investigator-driven, open, multicentre, cohort study; 887 smokers were enrolled in the programme. The intervention included intensive individual counselling as well as nicotine replacement and/or bupropion according to individual preferences. Re-interventions for relapse were offered during the 24-month follow-up. RESULTS: The abstinence rate was 37% at 24 months and did not differ among the various medication groups (p > 0.05 for all). Predictors of successful cessation were higher age (odds ratio, OR 1.47, 95% confidence interval, CI 1.08-2.00, p < 0.01), breathlessness on exertion (OR 2.26, 95% CI 1.1-4.9, p = 0.03), and a higher educational level (OR 1.81, 95% CI 1.06-3.09, p = 0.03). Higher Fagerström (OR 0.76, 95% CI 0.59-0.97, p < 0.01) and craving scores (OR 0.75, 95% CI 0.63-0.89, p < 0.01), chronic sputum production (OR 0.52, 95% CI 0.31-0.87, p = 0.01) and use of antidepressants (OR 0.54, 95% CI 0.32-0.91, p = 0.02) were associated with ongoing smoking. CONCLUSION: A comprehensive smoking cessation intervention at the workplace achieves high, stable, long-term abstinence rates. Elderly, well-educated employees with breathlessness on exertion have higher odds of quitting smoking. In contrast, those with high physical dependency and more intense craving, and those reporting use of antidepressant medication or sputum production have poorer chances to quit.

Tobacco harm reduction: the need for new products that can compete with cigarettes.

Over the last 50 years, the concept of tobacco harm reduction has been well established. It is now understood that nicotine itself is not very harmful and nicotine replacement therapy products have been widely used as an aid to quit, reduce to quit or temporarily abstain from smoking for many years. The popularity of the unlicensed electronic cigarette has increased despite an unknown risk profile and sinus use in Sweden provides strong evidence in support of a harm reduction strategy. The regulatory environment around harm reduction has changed in the UK and is continuing to evolve across the globe. The need for more appealing, licensed nicotine products capable of competing with cigarettes sensorially, pharmacologically and behaviourally is considered by many to be the way forward. The significant positive impact on public health that could be gained from encouraging people to switch from cigarettes to licensed medicinal nicotine products cannot be ignored.