Effect of menthol/mint-flavored pods on young JUUL E-cigarette users' subjective experience, puffing behavior, and nicotine exposure: A pilot study.

BACKGROUND: Recent regulations have banned all flavors except menthol/mint and classic tobacco from pod-based e-cigarette devices such as JUUL. However, menthol/mint flavor can present a potential risk given its increasing popularity among young people in the US and its puffing and nicotine-enhancing properties. This study examines the impact of menthol/mint flavor manipulation on users' puffing behavior, subjective experience, and nicotine exposure among young people. METHODS: JUUL users (n = 33, 18-24 years) attended two 60-min ad libitum e-cigarette use sessions (menthol/mint flavor vs. classic tobacco flavor) in a cross-over design. Puff topography and plasma nicotine concentration were measured, and participants completed subjective experience questionnaires. RESULTS: Following the use of the menthol/mint-flavored pod, increases were observed in measures of satisfaction, pleasurable/interest to use, willingness to use again, enjoyment, urge to vape, product appeal, taste, and concentration (p < .05 for all). For example, compared to the classic tobacco flavor, participants experienced significantly more satisfaction of the product (4.24 vs. 3.09; p = .001) and sensation enjoyment of the product (3.55 vs. 2.48; p = .002) when using the menthol/mint flavor. While means of the plasma nicotine boost and puff parameters were lower in the classic tobacco condition compared to the menthol/mint flavor condition, no statistical significance was observed between the two conditions (p > .05 for all). CONCLUSIONS: Results of this pilot study suggest that menthol/mint-flavor increases e-cigarette users' subjective experience significantly. Regulating menthol/mint flavor is a potentially promising strategy to curb e-cigarette use among young people.

Triangulating abuse liability assessment for flavoured cigar products using physiological, behavioural economic and subjective assessments: a within-subjects clinical laboratory protocol.

INTRODUCTION: In the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability. METHODS AND ANALYSES: Participants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18-25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models. ETHICS AND DISSEMINATION: The Virginia Commonwealth University Institutional Review Board approved the study (VCU IRB: HM20007848). Dissemination channels for study findings include scientific journals, scientific meetings, and policy briefs. TRIAL REGISTRATION NUMBER: NCT02937051.

Plasma and saliva levels of three metals in waterpipe smokers: a case control study.

In this case-control study, the influence of waterpipe tobacco smoking on the plasma and saliva levels of cadmium, lead and zinc was examined in participants who were waterpipe tobacco smokers (WS) or never-smokers (NS). The concentration of metals was higher in WS relative to NS. The mean (SEM) cadmium concentration in plasma was 3.3 (0.18) µg/dL in WS versus 0.82 (0.09) µg/L in NS (p < .001) and in saliva was 5.1 (0.36) µg/L in WS versus 0.64 (0.2) µg/L in NS (p < .001). The mean (SEM) lead concentration in plasma was 5.2 (0.25) µg/dL in WS versus 3.4 (0.41) µg/dL in NS (p < .01) and in saliva was 4.8 (0.58) µg/L in WS versus 2.8 (0.27) µg/L in NS (p < .05). Similarly, a significant difference in zinc concentration was observed, with a mean of 2.0 (0.17) µg/mL in WS plasma versus 1.49 (0.16) µg/mL in NS (p < .05) and a mean 0.94 (0.07) µg/mL in WS saliva versus 0.45 (0.06) µg/mL in NS (p < .01). In conclusion, waterpipe tobacco smoking is associated with elevated levels of metals in body fluids. These results provide another demonstration of how waterpipe tobacco smoking exposes smokers to harmful toxicants.

Warning Statements and Safety Practices Among Manufacturers and Distributors of Electronic Cigarette Liquids in the United States.

Introduction: Prior to the US Food and Drug Administration's (FDA) regulation of electronic cigarettes and warning statements related to nicotine addiction, there was no critical examination of manufacturer/distributor voluntary practices that could potentially inform FDA actions aimed to protect consumers. This study examined the content of warning statements and safety characteristics of electronic cigarette liquid bottles using a national sample. Methods: Research staff randomly selected four electronic cigarette liquid manufacturers/distributors from four US geographic regions. Staff documented the characteristics of product packaging and content of warning statements on 147 electronic cigarette liquids (0-30 mg/ml of nicotine) purchased online from 16 manufacturers/distributors in April of 2016. Results: Data showed that 97.9% of the electronic cigarette liquid bottles included a warning statement, most of which focused on nicotine exposure rather than health. Only 22.4% of bottles used a warning statement that indicated the product "contained nicotine." Of bottles that advertised a nicotine-based concentration of 12 mg/ml, 26% had a warning statements stated that the product "contains nicotine." None of the statements that indicated that the product "contained nicotine" stated that nicotine was "addictive." All bottles had a safety cap and 12% were in plastic shrink-wrap. Fifty-six percent of the websites had a minimum age requirement barrier that prevented under-aged persons from entering. Conclusions: Most manufacturers/distributors printed a warning statement on electronic cigarette liquid bottles, but avoided warning consumers about the presence and the addictiveness of nicotine. Studies are needed to examine manufacturer/distributor modifications to product packaging and how packaging affects consumer behaviors. Implications: These data can inform future FDA requirements related to the packaging and advertising of e-cigarette liquids; regulation related to the content of warning statements, including exposure warning statements, which are not currently mandated; and requirements on websites or language on packaging to help manufacturers adhere to the minimum age of purchase regulation. The data can also be used to help FDA develop additional guidance on the framing of statements on packaging that helps consumers make informed decisions about purchasing the product or protecting young people from use or unintentional exposure to the product.

Effect of Flavors and Modified Risk Messages on E-cigarette Abuse Liability.

OBJECTIVES: To measure e-cigarettes' abuse liability compared to conventional tobacco cigarettes under flavor and message conditions amenable to regulation. METHODS: Two studies used 2×2 within-subjects designs with factors of e-cigarette flavor (Study 1: tobacco vs. menthol; Study 2: cherry vs. unflavored) and message (Study 1: reduced harm vs. no message; Study 2: reduced exposure to carcinogens vs. no message) with cigarette smokers (N(total) = 36). Linear mixed effects models assessed abuse liability for tobacco products. Outcomes included the price after which consumption is zero (the maximum amount participants would pay for a tobacco product) from the multiple choice procedure (MCP) and cigarette purchase task (CPT) and demand elasticity (price sensitivity) from the CPT. RESULTS: In the MCP, the price where consumption reached zero was significantly lower in all e-cigarette conditions except tobacco flavor (message or no message) compared to cigarettes (p < .05 each). Demand elasticity was significantly higher for menthol/no message and unflavored/reduced exposure message conditions relative to cigarettes (p < .05 each). CONCLUSIONS: Flavors and modified risk messages included with e-cigarettes may affect e-cigarette abuse liability among smokers, suggesting regulatory pathways to influence demand for conventional and alternative tobacco products.

NIH electronic cigarette workshop: developing a research agenda.

BACKGROUND: Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood. PURPOSE: This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-cigarettes and conventional cigarettes. RESULTS AND CONCLUSIONS: The research needs identified by the workshop participants included the following: standards to measure the contents and emissions of e-cigarettes; biomarkers of exposure; physiological effects of e-cigarettes on tissues and organ systems, including pulmonary and cardiovascular; information on e-cigarette users, how the devices are used, and identification of the best tools to assess these measures; factors that drive use and influence patterns of use; and appropriate methods for evaluating a potential role for e-cigarettes in smoking or nicotine cessation. To understand fully the challenges and the opportunities that e-cigarettes represent, expertise will be needed in basic, behavioral, translational, and clinical sciences.

Significance of smoking machine toxicant yields to blood-level exposure in water pipe tobacco smokers.

BACKGROUND: The global increase in tobacco smoking with a water pipe (hookah, narghile, or shisha) has made understanding its health consequences imperative. One key to developing this understanding is identifying and quantifying carcinogens and other toxicants present in water pipe smoke. To do so, the toxicant yield of machine-generated water pipe smoke has been measured. However, the relevance of toxicant yields of machine-generated smoke to actual human exposure has not been established. METHODS: In this study, we examined whether carbon monoxide (CO) and nicotine yields measured with a smoking machine programmed to replicate the puffing behavior of 31 human participants who smoked a water pipe could reliably predict these participants' blood-level exposure. In addition to CO and nicotine, yields of polyaromatic hydrocarbons, volatile aldehydes, nitric oxide (NO), and "tar" were measured. RESULTS: We found that when used in this puff-replicating manner, smoking machine yields are highly correlated with blood-level exposure (nicotine: r > 0.76, P < 0.001; CO: r > 0.78, P < 0.001). Total drawn smoke volume was the best predictor of toxicant yield and exposure, accounting for approximately 75% to 100% of the variability across participants in yields of NO, CO, volatile aldehydes, and tar, as well as blood-level CO and normalized nicotine. CONCLUSIONS: Machine-based methods can be devised in which smoke toxicant yields reliably track human exposure. IMPACT: This finding indicates the basic feasibility of valid analytic laboratory evaluation of tobacco products for regulatory purposes.

A clinical laboratory model for evaluating the acute effects of electronic "cigarettes": nicotine delivery profile and cardiovascular and subjective effects.

BACKGROUND: Electronic "cigarettes" are marketed to tobacco users as potential reduced exposure products (PREP), albeit with little information regarding electronic cigarette user toxicant exposure and effects. This information may be obtained by adapting clinical laboratory methods used to evaluate other PREPs for smokers. METHODS: Thirty-two smokers participated in four independent Latin-square ordered conditions that differed by product: own brand cigarette, "NPRO" electronic cigarettes (NPRO EC; 18 mg cartridge), "Hydro" electronic cigarettes (Hydro EC; 16 mg cartridge), or sham (unlit cigarette). Participants took 10 puffs at two separate times during each session. Plasma nicotine and carbon monoxide (CO) concentration, heart rate, and subjective effects were assessed. RESULTS: Own brand significantly increased plasma nicotine and CO concentration and heart rate within the first five minutes of administration whereas NPRO EC, Hydro EC, and sham smoking did not. Own brand, NPRO EC, and Hydro EC (but not sham) significantly decreased tobacco abstinence symptom ratings and increased product acceptability ratings. The magnitude of symptom suppression and increased acceptability was greater for own brand than for NPRO EC and Hydro EC. CONCLUSIONS: Under these acute testing conditions, neither of the electronic cigarettes exposed users to measurable levels of nicotine or CO, although both suppressed nicotine/tobacco abstinence symptom ratings. IMPACT: This study illustrates how clinical laboratory methods can be used to understand the acute effects of these and other PREPs for tobacco users. The results and methods reported here will likely be relevant to the evaluation and empirically based regulation of electronic cigarettes and similar products.

Prevalence of and associations with waterpipe tobacco smoking among U.S. university students.

BACKGROUND: Although waterpipe tobacco smoking seems to be increasing on U.S. university campuses, these data have come from convenience samples. PURPOSE: We aimed to determine the prevalence of and associations with waterpipe tobacco smoking among a random sample of students. METHODS: We surveyed a random sample of graduate and undergraduate students at a large, urban university. We used multivariate modeling to determine independent associations between belief-related predictors and waterpipe tobacco smoking. RESULTS: Of the 647 respondents, waterpipe smoking was reported in 40.5%, over the past year in 30.6%, and over the past 30 days in 9.5%. Over half of the sample (52.1%) perceived that tobacco smoking from a waterpipe was less addictive than cigarette smoking. In fully adjusted multivariate models, 1-year waterpipe smoking was associated with low perceived harm (OR = 2.54, 95% CI = 1.68, 3.83), low perceived addictiveness (OR = 4.64, 95% CI = 3.03, 7.10), perception of high social acceptability (OR = 20.00, 95% CI = 6.03, 66.30), and high perception of popularity (OR = 4.72, 95% CI = 2.85, 7.82). CONCLUSIONS: In this sample, lifetime waterpipe use was as common as lifetime cigarette use. Perception of harm, perception of addictiveness, social acceptability, and popularity were all strongly related to waterpipe smoking.

Flavor improvement does not increase abuse liability of nicotine chewing gum.

Because the taste of nicotine gum has impeded compliance with dosing recommendations, nicotine gum with improved taste (mint, orange) was developed and marketed. Prior to marketing, the Food and Drug Administration (FDA) required a rigorous abuse liability assessment to examine whether enhanced palatability of nicotine gum would increase its abuse liability. Subjective, physiological, and psychomotor effects of mint flavor and original nicotine gum were tested in adult smokers (22-55 years old); a group of younger subjects (18-21 years old) was also included to allow for assessment of abuse liability in young adults specifically. Amphetamine and confectionery gum served as positive controls for abuse liability and palatability. Subjects rated palatability of mint gum higher than original nicotine gum, but substantially lower than confectionery gum. Palatability decreased with increasing dose of nicotine. Neither original nor mint gum increased ratings of traditional abuse liability predictors [Good Effect, Like Effect, Morphine-Benzedrine Group (MBG) scales of Addiction Research Center Inventory (ARCI)], while amphetamine increased ratings of all these measures. Both flavors of nicotine gum decreased craving during 2 h of abstinence. These effects were more pronounced in the adult group and mint gum was more effective than original gum. Younger subjects reported fewer withdrawal symptoms and lower ratings for drug effects and flavor. Improved flavor of nicotine gum does not increase abuse liability, but may be associated with enhanced craving reduction.