Switching Away From Smoking and Reduction in Cigarette Consumption among US Adult Purchasers of the JUUL System across 24 Months Including Diverse Subpopulations Disproportionately Affected by Cigarette Smoking.

OBJECTIVES: Electronic nicotine delivery systems (ENDS) can reduce tobacco-related health risks for adults who smoke cigarettes (AWS) by facilitating complete switching away from cigarettes. However, little is known about ENDS use and switching among subpopulations that have been disproportionately affected by smoking. METHODS: AWS (age≥21 years) were recruited following their first purchase of a JUUL Starter Kit in 2018. Participants self-reported switching (no past-30-day cigarette smoking) at 1-, 2-, 3-, 6-, 9-, 12-, 15-, 18-, 21-, and 24-month follow-ups. Percent switched and percent with substantial smoking reduction (≥50% decrease in cigarettes/day among those who continued smoking) were calculated. Analyses focused on racial/ethnic minorities, persons with low income and education levels, sexual minorities, and those with mental and physical health conditions. RESULTS: Overall rates of switching away from cigarettes increased across follow-ups to 51.2% (Month-12) to 58.6% (Month-24, 87% of whom used ENDS). Among those who continued to smoke at 24 months, 45.4% reduced cigarettes/day by ≥50%. Rates of switching and substantial smoking reduction were largely similar across subgroups, with some statistically significant, but small, differences in Month-24 switching rates(e.g. education, mental/physical health conditions; switch rate range: 42~57%). CONCLUSIONS: AWS demonstrated progressively increasing switching rates over two years after purchasing JUUL products. Similar trends in switching and smoking reduction were observed across populations disproportionately affected by smoking. By facilitating switching and smoking reduction, ENDS products such as JUUL may provide an opportunity to reduce smoking-related harm among some populations disproportionately affected by smoking, potentially reducing tobacco-related health disparities. IMPLICATIONS: ENDS have the potential to benefit population health if they can replace cigarettes. This benefit must extend to populations disproportionately affected by smoking. In this real-world study, 59% of JUUL purchasers reported complete switching two years later (no past-30-day smoking, with most continuing to use ENDS). Further, 45% of those who continued to smoke reduced cigarette consumption by at least half. These rates of switching and smoking reduction were largely comparable across populations disproportionately affected by smoking (defined, e.g., by ethnicity and income). ENDS can serve as an effective harm reduction strategy to complement current efforts to reduce tobacco-related disparities.

Comparing Adult Smokers Who Switched to JUUL versus Continuing Smokers: Biomarkers of Exposure and of Potential Harm and Respiratory Symptoms.

OBJECTIVES: Real-world evidence on exposure to harmful and potentially harmful constituents (HPHCs) and on biological effects in cigarette smokers who switch to electronic nicotine delivery systems (ENDS) can inform the health effects of switching. AIMS AND METHODS: This cross-sectional, observational study assessed adults who had smoked ≥10 cigarettes/day for ≥10 years, comparing 124 continuing cigarette smokers (Smokers) to 140 former smokers who switched to JUUL-brand ENDS exclusively for ≥6 months (Switchers). Assessments included biomarkers of exposure (BOEs) to select HPHCs, biomarkers of potential harm (BOPHs) related to smoking-related diseases, psychometric assessments of dependence on cigarettes and ENDS, respectively, and respiratory symptoms. Planned analyses compared geometric means, adjusted for demographic covariates; further analyses adjusted for additional lifestyle and smoking history covariates. RESULTS: Nicotine levels were significantly higher in Switchers (median time switched = 3 years), who were unusually heavy users of JUUL. All other BOEs, including NNAL and HPMA3 (primary endpoints), were significantly lower in Switchers than Smokers. Most BOPHs (sICAM-1 [primary], and eg, white blood cell count, MCP1, HbA1c) were significantly lower in Switchers than Smokers; HDL was significantly higher. Switchers reported significantly lower dependence on JUUL than Smokers did on cigarettes, and respiratory symptom scores were significantly lower among Switchers than Smokers. CONCLUSIONS: Compared to continuing smokers, smokers who switched to JUUL had substantially lower exposures to multiple HPHCs, favorable differences in markers of inflammation, endothelial function, oxidative stress, and cardiovascular risk, and fewer respiratory symptoms. These findings suggest that switching from cigarettes to JUUL likely reduces smokers' health risks. IMPLICATIONS: Short-term confinement studies and randomized clinical trials demonstrate that adult smokers who switch completely to ENDS experience substantial reductions in exposure to many smoking-related toxicants. This study extends those findings to longer periods of switching to JUUL-brand ENDS (almost 3 years on average) under naturalistic use conditions in real-world settings and also found that switching to JUUL resulted in favorable differences in BOPHs more proximally related to smoking-induced disease, as well as in respiratory symptoms. Smokers who switch to ENDS reduce their exposure to toxicants, likely reducing their disease risk.

Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette.

Background: Electronic nicotine delivery systems (ENDS) have the potential to benefit public health if smokers completely switch from cigarettes to ENDS. Methods: A cohort of adult smokers (age ≥ 21) who purchased a JUUL Starter Kit was followed for 12 months after the initial purchase. We defined "switching" as past-30-day abstinence from smoking (even if JUUL use had stopped), and analyzed factors associated with achievement and maintenance of self-reported repeated point-prevalence switching (RPPS) at three follow-ups, i.e., no past-30-day smoking at months 6, 9, and 12. Results: RPPS was reported by 21.6% of the 12,537 evaluable smokers. Smokers with lighter smoking history and lower cigarette dependence at baseline were more likely to report RPPS. RPPS was also associated with daily use of JUUL (Month-3: OR = 2.32, 95% CI = 2.02-2.68; Month-6: OR = 1.73, 95% CI = 1.42-2.10), and with greater subjective reinforcing effects from JUUL use (assessed by the mCEQ, Month-3: OR = 1.46, 95% CI = 1.38-1.56; Month-6: OR = 1.11; 95% CI = 1.02-1.20). Even among smokers who did not meet the criteria of RPPS (i.e., who smoked at least once), 35.5% reported past 30-day point-prevalence switching on at least one follow-up, and their cigarette consumption was substantially reduced compared to baseline. Conclusions: Approximately one-fifth of adult smokers reported 30-day point-prevalence abstinence at 6, 9, and 12 months after purchasing JUUL. Greater use of JUUL and stronger subjective reinforcing effects were associated with nonsmoking, validating the potential for ENDS to substitute for smoking, with potential for positive impacts on individual and population health.

Reply to Commentary on "Adult Smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months After Initially Purchasing a JUUL e-Cigarette" and the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study.

BACKGROUND: This is authors' reply to the Commentary on our publication entitled "Adult smokers' Complete Switching Away from Cigarettes at 6, 9, and 12 Months after Initially Purchasing a JUUL e-Cigarette." METHODS AND RESULTS: Analyses addressed questions about follow-up rates and missed responses in the Adult JUUL Switching and Smoking Trajectories (ADJUSST) Study. Results demonstrate limited potential for selection bias, as participants who missed surveys were similar to those with complete data, and re-contact of participants who missed a follow-up indicated almost half were not smoking. Imputing smoking behavior for missing data would likely introduce bias and is not appropriate. The study demonstrated that JUUL products can facilitate high rates of complete switching away from cigarettes as suggested in previous experimental and observational studies. The ADJUSST cohort, including baseline nonsmokers, demonstrates a net reduction in smoking prevalence. Moreover, population modeling considering both benefits and harms demonstrated a net population benefit. CONCLUSION: While the ADJUSST Study is not without limitations, the findings are consistent with multiple streams of real-world evidence that indicate that ENDS can facilitate switching among adults who smoke, and provide population benefits.

An Open-Label, Randomized, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers.

INTRODUCTION: This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes in 24 adult smokers. METHODS: At five study visits, subjects used either the JS in 59 mg/mL, JS 18 mg/mL (two visits), and JS 9 mg/mL (all tobacco-flavored) or smoked their UB cigarette first during a controlled puffing sequence (CPS) and then ad libitum (5 min) use sessions. Blood samples were taken at specified timepoints for 60 min in each session. The modified Product Evaluation Scale assessed subjective effects 30-min post-use in the CPS session. RESULTS: Maximum plasma nicotine concentration (Cmax-BL), total nicotine exposure (AUC0-60-BL), and rate of plasma nicotine rise were significantly lower for all JS products compared to subjects' UB cigarette in CPS and ad libitum use sessions. In both use sessions these PK parameters were significantly higher for JS 59 mg/mL compared to 18 and 9 mg/mL. Subjective measures of cigarette craving relief and "Enough Nicotine" for JS 59 mg/mL did not differ significantly from UB cigarettes, but JS 18 and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes. CONCLUSIONS: Nicotine exposure and subjective relief were directly related to JS nicotine concentration: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving. Heavier and more dependent smokers may require the greater nicotine delivery of JS 59 mg/mL to successfully transition away from cigarettes. IMPLICATIONS: It has been suggested that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes may facilitate smokers transitioning away from cigarettes. We examined nicotine PK and subjective effects of JUUL System (JS) ENDS with three nicotine concentrations (59, 18 and 9 mg/mL) compared to combustible cigarettes. Nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. These findings suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes.

Changes in Biomarkers of Cigarette Smoke Exposure After 6 Days of Switching Exclusively or Partially to Use of the JUUL System with Two Nicotine Concentrations: A Randomized Controlled Confinement Study in Adult Smokers.

INTRODUCTION: Evidence suggests that cigarette smokers who switch to electronic nicotine delivery systems (ENDS) reduce their exposure to harmful toxicants and carcinogens. It is unclear if dual-use is associated with decreases in exposure to toxicants. METHODS: This parallel-group confinement study assessed changes in biomarkers of exposure (BOEs) over six days among healthy adult smokers who were randomized into 1 of 11 study groups: eight JUUL-brand System (JUUL) groups (4 JUUL flavors [Virginia Tobacco, Menthol, Mint, Mango] × 2 nicotine concentrations [5.0% or 3.0% by weight]); Dual-Use group used preferred JUUL flavor (5.0% nicotine) and ≤50% usual brand (UB) cigarettes/day; UB Cigarette group and one group abstained from all tobacco/nicotine product use (Abstinence group). Urine and blood analysis assessed changes in primary BOE endpoints (NNAL, 3-HPMA, MHBMA, S-PMA COHb) and secondary BOE endpoints (NNN, HMPMA, CEMA, 1-OHP, O-toluidine, 2-NA, 4-ABP) among 279 adult smokers. RESULTS: In JUUL groups, median percent reductions in primary BOEs (Day 6-Baseline) were 90%-≥100% of Abstinence; there were no significant differences between JUUL groups and Abstinence. All reductions in JUUL groups were substantially and statistically significantly greater than reductions in the UB Cigarette group (ps < 0.025). Median reductions in primary BOEs in the Dual-Use group were 43%-55% of Abstinence. Similar results were observed for secondary BOEs. CONCLUSION: This study suggests that the use of JUUL as a complete or partial substitute (i.e., dual-use with ≥50% reduction in cigarette consumption) for combustible cigarettes can substantially reduce exposure to multiple toxins associated with cigarette smoking. IMPLICATIONS: This study adds to the growing body of evidence supporting the utility of ENDS products as potentially reduced-harm alternatives to cigarettes for adult smokers. Adult smokers who switched completely from cigarette smoking to use of the JUUL System ("JUUL") in two nicotine concentrations (5.0% and 3.0%) and four flavors significantly reduced their exposure to multiple classes of cigarette-related toxicants. Additionally, smokers who used JUUL and continued smoking but reduced their daily cigarette consumption by ≥50% (dual users) also significantly reduced their toxicant exposure compared to cigarette smoking.

Differences in Switching Away From Smoking Among Adult Smokers Using JUUL Products in Regions With Different Maximum Nicotine Concentrations: North America and the United Kingdom.

INTRODUCTION: Electronic nicotine delivery systems (ENDS) may improve public health if they facilitate smokers switching away from cigarettes. Conceptually, switching is facilitated when ENDS provide adequate nicotine delivery. Switching rates among smokers who purchased the JUUL System ("JUUL") were compared in the United Kingdom (UK), where regulations limit nicotine concentration to 20 mg/mL versus North America (N.Am.; United States and Canada), where higher concentrations are available. AIMS AND METHODS: Adult established smokers (age ≥21, smoked ≥100 cigarettes, smoking some days or every day at baseline) who newly purchased JUUL were recruited into a longitudinal study (UK: N = 1247; N.Am.: N = 8835). Complete switching (no smoking for ≥30 days) was assessed 1, 3, and 6 months after purchase; propensity score matching (PSM) and logistic regression compared switching after adjusting for baseline characteristics. RESULTS: In both N.Am. and UK, ≥82% of participants reported using the highest JUUL nicotine concentration available (UK: 18 mg/mL; N.Am.: 59 mg/mL). Unadjusted switching rates did not differ at 1 month (17%-18%); unadjusted and adjusted rates were significantly higher in N.Am. (vs. UK) at 3 and 6 months. In the PSM sample, after additional covariate adjustment, rates were significantly higher in N.Am. (vs. UK) at 3 months (31.5% vs. 22.7%; odds ratio [95% confidence interval, CI] = 1.59 [1.25, 2.02]) and 6 months (38.0% vs. 26.0%; odds ratio [95% CI] = 1.79 [1.37, 2.35]). CONCLUSIONS: These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Differences in smoking and ENDS use characteristics did not explain associations of location and switching; however, between-country differences may be affected by unmeasured factors. IMPLICATIONS: Switching rates were lower among smokers who purchased the JUUL System ("JUUL") in the UK, where regulations limit nicotine concentration to 20 mg/mL versus N.Am. (United States and Canada), where higher concentrations are available-before and after controlling for differences in smoking and ENDS use characteristics. These results suggest availability of ENDS in nicotine concentrations greater than 20 mg/mL may be associated with increased switching among adult smokers. Between-country differences may be affected by unmeasured factors; future research should consider these factors and the extent to which regulatory policy environments may explain differences in switching among adult smokers.

Validation of a behavioral economic purchase task for assessing drug abuse liability.

Behavioral economic purchase tasks quantify drug demand (i.e. reinforcing value of a drug) and have been used extensively to assess the value of various drugs among current users. However, purchase tasks have been rarely used with unfamiliar drugs to address a compound's abuse liability, and the current study sought to validate the paradigm in this capacity. Using a double-blind placebo-controlled within-subjects drug challenge design, the study evaluated differential drug demand on an experimental drug purchase task for a 20 mg dose of oral D-amphetamine (versus placebo), a prototypic psychostimulant, in 98 stimulant-naïve participants. Compared with placebo, amphetamine significantly increased intensity, breakpoint and Omax , and significantly decreased elasticity. Mechanistic analyses revealed that Omax and breakpoint mediated the relationship between subjective drug effects and 'willingness to take again', a putative indicator of liability via motivation for future drug-seeking behavior. These findings validate the purchase task paradigm for quantifying the reinforcing value and, in turn, abuse liability of unfamiliar compounds, providing a foundation for a variety of future applications.

Characterizing Polytobacco Use Trajectories and Their Associations With Substance Use and Mental Health Across Mid-Adolescence.

Background: Polytobacco product use is suspected to be common, dynamic across time, and increase risk for adverse behavioral outcomes. We statistically modeled characteristic types of polytobacco use trajectories during mid-adolescence and tested their prospective association with substance use and mental health problems. Methods: Adolescents (N = 3393) in Los Angeles, CA, were surveyed semiannually from 9th to 11th grade. Past 6-month combustible cigarette, e-cigarette, or hookah use (yes/no) over four assessments were analyzed using parallel growth mixture modeling to identify a parsimonious set of polytobacco use trajectories. A tobacco product use trajectory group was used to predict substance use and mental health at the fifth assessment. Results: Three profiles were identified: (1) tobacco nonusers (N = 2291, 67.5%) with the lowest use prevalence (<3%) of all products across all timepoints; (2) polyproduct users (N = 920, 27.1%) with moderate use prevalence of each product (8-35%) that escalated for combustible cigarettes but decreased for e-cigarettes and hookah across time; and (3) chronic polyproduct users (N = 182, 5.4%) with high prevalence of each product use (38-86%) that escalated for combustible cigarettes and e-cigarettes. Nonusers, polyproduct users, and chronic polyproduct users reported successively higher alcohol, marijuana, and illicit drug use and ADHD at the final follow-up, respectively. Both tobacco using groups (vs. nonusers) reported greater odds of depression and anxiety at the final follow-up but did not differ from each other. Conclusions: Adolescent polytobacco use may involve a common moderate risk trajectory and a less common high-risk chronic trajectory. Both trajectories predict substance use and mental health symptomology. Implications: Variation in use and co-use of combustible cigarette, e-cigarette, and hookah use in mid-adolescence can be parsimoniously characterized by a small set common trajectory profiles in which polyproduct use are predominant patterns of tobacco product use, which predict adverse behavioral outcomes. Prevention and policy addressing polytobacco use (relative to single product use) may be optimal tobacco control strategies for youth, which may in turn prevent other forms of substance use and mental health problems.

Associations of ADHD Symptoms With Smoking and Alternative Tobacco Product Use Initiation During Adolescence.

Objective: Recently, use of alternative tobacco products, such as electronic cigarettes (e-cigarettes) and hookah (water-pipe tobacco), has increased among adolescents. It is unknown whether attention-deficit hyperactivity disorder (ADHD) symptoms are associated with initiation of alternative tobacco product use. Methods: Ninth grade high school students who never used any tobacco product at baseline (N = 1,921) participated in a longitudinal survey from 2014 to 2015. Overall symptomatology and inattention (IN) and hyperactivity-impulsivity (HI) ADHD subtypes were assessed at baseline. Past 6-month e-cigarette, hookah, and combustible cigarette use (yes/no) were reported at three semi-annual follow-ups. Repeated measures logistic regression models assessed the association of baseline ADHD symptoms with likelihood of tobacco product initiation across follow-ups. Results: For ADHD main effect estimates, unadjusted odds of reporting e-cigarette, hookah, and combustible cigarette use pooled across follow-up time points were 45%, 33%, and 37% greater, respectively, with each increase in one SD-unit of baseline ADHD symptoms in baseline never-users of tobacco products. ADHD was not associated with hookah or combustible cigarette use after adjusting for other risk factors. After adjustment, e-cigarette use initiation remained associated with overall ADHD (odds ratio, OR [95%confidence interval, 95% CI] = 1.22 [1.04, 1.42]) and HI (OR [95% CI] = 1.26 [1.09, 1.47]) symptoms, but not IN symptoms (OR [95% CI] = 1.13 [0.97, 1.32]). ADHD × Time interactions were not significant, suggesting ADHD increased odds of e-cigarette use initiation but did not alter the shape of use trajectory across follow-up among initiators. Conclusions: Understanding the psychosocial mechanisms underlying the pathway from ADHD to e-cigarette use may advance tobacco product use etiologic theory and prevention practice in the current era in which e-cigarette use is popular among youth.

Association of Digital Media Use With Subsequent Symptoms of Attention-Deficit/Hyperactivity Disorder Among Adolescents.

Importance: Modern digital platforms are easily accessible and intensely stimulating; it is unknown whether frequent use of digital media may be associated with symptoms of attention-deficit/hyperactivity disorder (ADHD). Objective: To determine whether the frequency of using digital media among 15- and 16-year-olds without significant ADHD symptoms is associated with subsequent occurrence of ADHD symptoms during a 24-month follow-up. Design, Setting, and Participants: Longitudinal cohort of students in 10 Los Angeles County, California, high schools recruited through convenience sampling. Baseline and 6-, 12-, 18-, and 24-month follow-up surveys were administered from September 2014 (10th grade) to December 2016 (12th grade). Of 4100 eligible students, 3051 10th-graders (74%) were surveyed at the baseline assessment. Exposures: Self-reported use of 14 different modern digital media activities at a high-frequency rate over the preceding week was defined as many times a day (yes/no) and was summed in a cumulative index (range, 0-14). Main Outcomes and Measures: Self-rated frequency of 18 ADHD symptoms (never/rare, sometimes, often, very often) in the 6 months preceding the survey. The total numbers of 9 inattentive symptoms (range, 0-9) and 9 hyperactive-impulsive symptoms (range, 0-9) that students rated as experiencing often or very often were calculated. Students who had reported experiencing often or very often 6 or more symptoms in either category were classified as being ADHD symptom-positive. Results: Among the 2587 adolescents (63% eligible students; 54.4% girls; mean [SD] age 15.5 years [0.5 years]) who did not have significant symptoms of ADHD at baseline, the median follow-up was 22.6 months (interquartile range [IQR], 21.8-23.0, months). The mean (SD) number of baseline digital media activities used at a high-frequency rate was 3.62 (3.30); 1398 students (54.1%) indicated high frequency of checking social media (95% CI, 52.1%-56.0%), which was the most common media activity. High-frequency engagement in each additional digital media activity at baseline was associated with a significantly higher odds of having symptoms of ADHD across follow-ups (OR, 1.11; 95% CI, 1.06-1.16). This association persisted after covariate adjustment (OR, 1.10; 95% CI, 1.05-1.15). The 495 students who reported no high-frequency media use at baseline had a 4.6% mean rate of having ADHD symptoms across follow-ups vs 9.5% among the 114 who reported 7 high-frequency activities (difference; 4.9%; 95% CI, 2.5%-7.3%) and vs 10.5% among the 51 students who reported 14 high-frequency activities (difference, 5.9%; 95% CI, 2.6%-9.2%). Conclusions and Relevance: Among adolescents followed up over 2 years, there was a statistically significant but modest association between higher frequency of digital media use and subsequent symptoms of ADHD. Further research is needed to determine whether this association is causal.

Associations between ADHD symptoms and smoking outcome expectancies in a non-clinical sample of daily cigarette smokers.

BACKGROUND AND OBJECTIVES: Smoking outcome expectancies for positive reinforcement (PR: beliefs that smoking produces desirable outcomes) and negative reinforcement (NR: beliefs that smoking alleviates negative affect) are modifiable cognitive manifestations of affect-mediated smoking motivation. Based on prior data and theory, we hypothesized that NR and PR expectancies are associated with ADHD symptom levels in a non-clinical sample of cigarette smokers. (Am J Addict 2016; XX:XX -XX) METHODS: Daily cigarette smokers (N = 256) completed self-report measures of ADHD symptoms and smoking outcome expectancies. Cross-sectional associations of overall ADHD symptomatology and the ADHD symptom dimensions of inattention (IN: difficulty concentrating and distractibility) and hyperactivity impulsivity (HI: poor inhibitory control and motor activity restlessness) with PR and NR smoking outcome expectancies were examined. RESULTS: Higher levels of overall, IN and HI ADHD symptoms were positively associated with NR smoking expectancies after statistically controlling for anxiety, depression, alcohol/drug use problems, nicotine dependence, and other smoking expectancies. Although neither HI nor IN symptom dimensions exhibited empirically unique relations to NR expectancies over and above one another, the collective variance across IN and HI was associated with NR expectancies. PR expectancies were not associated with ADHD symptoms. DISCUSSION AND CONCLUSIONS: Although PR and NR expectancies may be important etiological influences in the overall population of smokers, NR outcome expectancies appear to be disproportionately expressed in smokers with elevated ADHD symptoms. Cognitive manifestations of NR motivation, which may be modifiable via intervention, are prominent in smokers with elevated ADHD symptoms. SCIENTIFIC SIGNIFICANCE: Beliefs that smoking alleviates negative affect may underlie ADHD-smoking comorbidity.

Randomized trial assessing the effect of the JUUL system on switching away from cigarettes and smoking reduction among U.S. adults who smoke cigarettes.

Observational studies show high rates of switching away from cigarettes among adult purchasers of JUUL-brand electronic nicotine delivery system (ENDS); data are needed to evaluate switching with JUUL in randomized general population trials. The association of ENDS flavor availability and switching is pertinent. This study assessed switch rates and smoking reduction among participants randomized to use JUUL in a choice of flavors or tobacco-only, compared to a condition provided smoking-cessation materials. U.S. adults who smoke cigarettes (N = 837; Mage [SD] = 45.99 years [11.48]; 18.76 cigarettes/day [SD = 7.86]; 50.2% female) from an address-based representative panel were randomized to receive JUUL for 6 months (5.0% nicotine; only Virginia Tobacco [N = 285] or choice of flavors [N = 281]), or smoking-cessation materials (quit advice [QA]; N = 271). Self-reported past 30-day smoking and cigarette consumption were assessed at 1, 3, and 6 months. Repeated-measure regressions assessed differences in smoking outcomes between groups. Only 2% of participants were planning to quit smoking within 30 days. Across the 6-month intervention, participants randomized to JUUL (vs. QA) had 6.57-fold greater odds of reporting past 30-day switching (95% CI [3.72-11.63]). Participants in the JUUL (vs. QA) group smoked 27% fewer cigarettes/day versus baseline (Rate Ratio [95% CI] = 0.73 [0.68-0.77]). Over half (51.8%) of the Virginia Tobacco group used other flavors (36.7% nontobacco flavors), contaminating randomized flavor-conditions. JUUL flavor groups did not differ in smoking outcomes (p > .48). Use of JUUL products may support complete switching away from cigarettes, including among those not ready to quit smoking. Results suggest a preference for nontobacco-flavored ENDS among adults who smoke, although smoking outcomes did not differ by flavor. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessment of abuse liability and switching potential of menthol-flavored pod-based electronic nicotine delivery systems among US adults who smoke cigarettes.

BACKGROUND: Menthol-flavored electronic nicotine delivery systems (ENDS) are a focus of public health and regulatory policy considerations. The abuse liability of five menthol-flavored pod-based ENDS was compared to combustible cigarettes, and switching potential of ENDS was also evaluated. METHODS: 215 US adults who smoke cigarettes (34.4% female; mean age[SD]=29.60[8.75]; 40.9% non-Hispanic White; mean cigarettes/day[SD]=12.04[8.52]) completed a randomized 6-arm within-person cross-over product-use study. Participants used five pod-based menthol-flavored ENDS (JUUL2 Polar Menthol 1.5%, JUUL2 Prototype Fresh Menthol 3.0%, JUUL Menthol 5.0%, Vuse Alto Menthol 5.0%, NJOY Ace Menthol 5.0%) and their usual brand (UB) cigarette for 20minutes ad libitum. After each product use, subjective reinforcing effects relevant to abuse liability and associated with switching away from cigarettes (e.g., satisfaction, product liking) were assessed. RESULTS: All ENDS products were rated substantially and statistically significantly lower than UB cigarette on measures of subjective reinforcing effects (ps<0.001). Satisfying effects of JUUL2 1.5% were rated significantly higher than other ENDS products. JUUL2 Prototype 3.0% and Vuse Alto 5.0% did not significantly differ (ps>0.05), and both were rated significantly higher than JUUL 5.0% and NJOY Ace 5.0% (ps<0.05). Differences in subjective responses to study products did not significantly differ by preference for menthol cigarettes or by current ENDS use. CONCLUSIONS: Abuse liability of all menthol-flavored ENDS in this study was substantially lower than combustible cigarettes. Abuse liability of JUUL2 1.5% was within the range of currently marketed pod-based menthol-flavored ENDS products. JUUL2 1.5% likely has high potential for facilitating switching among US adults who smoke.

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.

Background: Electronic nicotine delivery systems (ENDS) are substitute sources of nicotine for adults who smoke cigarettes. Understanding changes in dependence as people switch from cigarettes to ENDS is relevant to public health. This study assessed changes in dependence among adults who switched completely or partially (dual users) from cigarettes to JUUL-brand ENDS over 12 months. Methods: US adults who smoke and purchased a JUUL Starter Kit (n = 17,619) completed a baseline assessment and were invited to 1-, 2-, 3-, 6-, 9- and 12-month follow-ups. Dependence on cigarettes at baseline and on JUUL at follow-ups was assessed with the Tobacco Dependence Index (TDI; Range 1-5). Analyses estimated the minimal important difference (MID) for the scale, compared JUUL dependence to baseline cigarette dependence and assessed changes in JUUL dependence over 1-year, including among those using JUUL at all follow-ups. Results: Participants who switched at month 2 had month 1 JUUL TDI scores 0.24 points greater than those who continued smoking (p<0.001); thus MID=0.24. Among both switchers and dual users overall, dependence on JUUL 1 and 12 months later was lower than baseline dependence on cigarettes (ps<0.001); participants who smoked every day showed more consistent and larger reductions. Among participants who persistently used JUUL without smoking, dependence increased 0.01 points per month (p<0.001), but was leveling off over time. Conclusions: Dependence on JUUL was lower than baseline cigarette dependence. Increases in JUUL dependence were small over 12 months of continual JUUL use. These data indicate that ENDS, including JUUL, have lower dependence potential than cigarettes.

A New Questionnaire to Assess Respiratory Symptoms (The Respiratory Symptom Experience Scale): Quantitative Psychometric Assessment and Validation Study.

BACKGROUND: Smokers often experience respiratory symptoms (eg, morning cough), and those who stop smoking, including those who do so by switching completely to electronic nicotine delivery systems (ENDS), may experience reductions in symptoms. Existing respiratory symptom questionnaires may not be suitable for studying these changes, as they are intended for patient populations, such as those with chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study aimed to develop a respiratory symptom questionnaire appropriate for current smokers and for assessing changes when smokers stop smoking. METHODS: The Respiratory Symptom Experience Scale (RSES) was derived from existing instruments and subject matter expert input and refined through cognitive debriefing interviews (n=49). Next, for purposes of the quantitative psychometric evaluation, the RSES was administered to smokers (n=202), former smokers (no tobacco use in >6 months; n=200), and switchers (n=208, smokers who switched to ENDS for >6 months), all of whom had smoked for at least 10 years (mean age 33 years). Participants, who averaged 62 (SD 12) years of age, included 28% (173/610) with respiratory allergy symptoms and 17% (104/610) with COPD. Test-retest reliability was assessed by repeat assessment after 1 week in 128 participants. RESULTS: A generalized partial credit model confirmed that the response options were ordered, and a parallel analysis using principal components confirmed that the scale was unidimensional. With allowance for 2 sets of correlated errors between pairs of items, a 1-factor graded response model fit the data. Discrimination parameters were approximately 1 or greater for all items. Scale reliability was 0.80 or higher across a broad range of severity (standardized scores -0.40 to 3.00). Test-retest reliability (absolute intraclass correlation) was good, at 0.89. RSES convergent validity was supported by substantial differences (Cohen d=0.74) between those with and without a diagnosis of respiratory disease (averaging 0.57 points, indicating that differences of this size or smaller represent meaningful differences). RSES scores also strongly differentiated those with and without COPD (d=1.52). Smokers' RSES scores were significantly higher than former smokers' scores (P<.001). Switchers' RSES scores were significantly lower than smokers' scores (P<.001) and no different from former smokers' scores (P=.34). CONCLUSIONS: The RSES fills an important gap in the existing toolkit of respiratory symptom questionnaires; it is a reliable and valid tool to assess respiratory symptoms in adult current and former smokers, including those who have switched to noncombusted nicotine products. This suggests that the scale is sensitive to respiratory symptoms that develop in smokers and to their remission when smokers quit or switch to noncombusted nicotine products intended to reduce the harm of smoking. The findings also suggest that switching from cigarettes to ENDS may improve respiratory health.

Comparison of biomarkers of exposure among US adult smokers, users of electronic nicotine delivery systems, dual users and nonusers, 2018-2019.

The harm caused by cigarette smoking is overwhelmingly due to byproducts of tobacco combustion. Electronic Nicotine Delivery Systems (ENDS) provide nicotine to users without combustion, and may support tobacco harm reduction among cigarette smokers who would not otherwise quit in the near term. Analyses of Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study compared biomarkers of exposure (BOE) levels for nicotine, 3 metals, 2 tobacco-specific nitrosamines and 14 smoking-related volatile organic compounds in 151 exclusive ENDS users, 1341 exclusive cigarette smokers, 115 dual users (cigarettes and ENDS), and 1846 past 30-day nonusers of tobacco, adjusting for demographics. Nicotine exposure in ENDS users and dual users did not significantly differ from smokers. Among ENDS users, 16 of 18 other BOEs were significantly lower than smokers'; 9 BOEs were not significantly different from nonusers. Among dual users smoking < 10 cigarettes/day, 15 of 18 non-nicotine BOEs were significantly lower than smokers', whereas in dual users smoking ≥ 10 cigarettes per day none of the BOEs significantly differed from smokers'. In this representative sample of US adults, exclusive use of ENDS (vs. cigarette smoking) was associated with much lower exposures to many harmful chemicals associated with smoking-related disease. BOE levels in dual users were directly related to their cigarette consumption. These BOE data provide further evidence that ENDS expose users to substantially lower levels of toxicants than combustible cigarettes, confirming their potential for harm reduction.

Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System.

OBJECTIVES: Studies have assessed switching away from cigarettes among adult smokers who use electronic nicotine delivery systems (ENDS), but there is little data assessing differences in likelihood of switching or ENDS use characteristics by menthol smoking. METHODS: Adult (age ≥ 21) established smokers who purchased a JUUL Starter Kit (N = 15,036) completed baseline and 1-, 2-, 3-, 6-, 9- and 12-month assessments. Switching (no past-30-day cigarette smoking) and flavor use were assessed at each follow-up. Repeated-measure logistic regression models evaluated association of menthol smoking and switching across 1 year. RESULTS: Across the 6 follow-ups, more menthol smokers primarily used Menthol/Mint-flavored JUULpods (53.8%) than nonmenthol smokers (22.9%). Only 6.4% of menthol smokers primarily used Tobacco flavors (vs. 25.9% of nonmenthol smokers). Across all follow-ups menthol smokers (41.2% of sample) were more likely to switch than nonmenthol smokers (42.6% vs. 38.8%: OR [95% CI] = 1.17 [1.11, 1.23]); this association remained significant after adjustment for sociodemographic, smoking and JUUL use covariates (aOR [95% CI] = 1.13 [1.05, 1.21]). Nonmenthol smokers, but not menthol smokers, were significantly more likely to switch when primarily using Menthol/Mint-flavored (vs. Tobacco-flavored) JUULpods (aOR [95% CI] = 1.14 [1.04, 1.25]). Differences in baseline smoking characteristics between menthol and nonmenthol smokers were small in magnitude. CONCLUSIONS: Adult menthol (vs. nonmenthol) smokers using JUUL were more likely to switch. More than twice as many menthol (vs. nonmenthol) smokers primarily used Menthol/Mint-flavor JUULpods; few menthol smokers used tobacco flavors. Given these pronounced differences in flavor preferences, availability of ENDS in menthol flavors may be particularly important for menthol smokers, but may also benefit some nonmenthol smokers.

Pharmacokinetic and subjective assessment of prototype JUUL2 electronic nicotine delivery system in two nicotine concentrations, JUUL system, IQOS, and combustible cigarette.

RATIONALE: Electronic nicotine delivery systems and heated tobacco products are noncombustible alternatives for adult smokers. Evidence suggests sufficient nicotine delivery and satisfying effects are necessary to facilitate switching away from smoking; nicotine delivery varies across electronic nicotine delivery systems within limited nicotine concentrations. OBJECTIVES: To assess the nicotine delivery and subjective effects of prototype JUUL2 System in two nicotine concentrations, currently-marketed US JUUL System ("JUUL"), IQOS-brand heated tobacco product, and combustible cigarettes. METHODS: Adult smokers (N = 40) completed a 5-arm cross-over product-use laboratory confinement study. Nicotine pharmacokinetics and subjective effects were assessed following use of: (1) JUUL2 prototype 18 mg/mL nicotine; (2) JUUL2 prototype 40 mg/mL; (3) JUUL 59 mg/mL; (4) IQOS 18 mg/g; and (5) usual brand combustible cigarette, each evaluated during ad libitum (10 min) and controlled (5 min, 10 standardized puffs) use. RESULTS: Nicotine delivery was greatest for combustible cigarettes, followed by JUUL2 prototype 40 mg/mL, IQOS, JUUL2 prototype 18 mg/mL, and JUUL 59 mg/mL. Nicotine delivery from JUUL2 prototype 18 mg/mL was significantly greater than JUUL 59 mg/mL after ad libitum use. JUUL products were significantly more satisfying and effective at reducing craving than IQOS. JUUL2 prototype 40 mg/mL was significantly more aversive than other JUUL products. CONCLUSIONS: Prototype JUUL2 and JUUL 59 mg/mL products were rated higher than IQOS on subjective measures associated with switching away from smoking. The JUUL2 prototype 40 mg/mL produced aversive responses and would require modifications to be a viable product for adult smokers. Nicotine delivery and subjective responses to JUUL2 prototype 18 mg/mL suggest a product based on this prototype may facilitate increased switching among adult smokers.