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IntroductionThere has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood.MethodsMale and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from post-natal day (PND) 31-40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for volitional exposure to nicotine vapor (PND 285-395). Plasma nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session.ResultsGroup mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change the effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG-exposed females to nicotine vapor in a fixed ratio 5 challenge.ConclusionsRepeated adolescent nicotine vapor inhalation leads to enhanced liability for volitional exposure to nicotine vapor in adulthood in female rats, but minimal change in spontaneous locomotor behavior.ImplicationsThese results show that adolescent vaping of nicotine can lead to lasting sensitization to the effects of nicotine in adulthood, including volitional responding for nicotine vapor. Demonstration of this in a controlled animal model establishes causality in a manner not possible from longitudinal evidence in human populations. These findings further highlight the importance of decreasing adolescent nicotine exposure to e-cigarettes to reduce consumption in adulthood.

INTRODUCTION: The Society for Research on Nicotine and Tobacco began in the United States as a scientific organization to stimulate the generation and dissemination of new knowledge concerning nicotine and tobacco in all its manifestations. Now in its 30th year, the Society is taking on new challenges in tobacco control, nicotine vaping, product regulation, and public policy. AIMS AND METHODS: This Review describes the formative years of the Society from the perspective of researchers who were in leadership positions during that time, documenting how biobehavioral and clinical research in the first 10 years was a continuation of the scientific mission of the 1988 United States Surgeon Generals Report on Nicotine Addiction and summarizing organizational innovations during each presidents term of office. CONCLUSIONS: The Societys promotion of scientific research served as a catalyst for funding, policy, and regulation, setting the stage for its influence and credibility. IMPLICATIONS: This Commentary provides context and an overview of the scientific research and the organizational innovations that occurred during the early years of the Society for Research on Nicotine and Tobacco using publications and available documentation. The Society was able to thrive because biobehavioral research on nicotine addiction provided the scientific underpinnings for the tobacco control enterprise as a whole. The objective of this Commentary is to describe formative events in the Societys history based on the accomplishments of its early leaders.

IntroductionCigars are currently the second-highest-used combustible tobacco product among U.S. adults, but knowledge about health effects of premium cigars versus other cigar subtype use is limited.Aims and methodsThis study analyzed the biospecimen data (n = 31 875) from Waves 1-5 of the Population Assessment of Tobacco and Health Study, collected during 2013-2019. Multivariable generalized estimation equations, accounting for within-person clustering, were conducted to examine differences in urine biomarkers of exposure (BOE) from five classes of harmful and potentially harmful constituents along with a biomarker of oxidative stress (urine 8-isoprostane) among exclusive users of premium cigars versus other exclusive cigar subtypes (ie, non-premium large cigars, cigarillos, and filtered cigars), cigarettes, and non-tobacco users.ResultsIn comparison to non-tobacco users, exclusive premium cigar users had higher geometric mean concentrations of the nicotine metabolite cotinine (5.8 vs. 0.5ng/mg, p

IntroductionThis study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes.Aims and methodsIn 2019-2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined.ResultsOf 100 participants (64% male, 71% in the 18-34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%-6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1-2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE.ConclusionsNicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes.ImplicationsThe study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.

IntroductionAvailable evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown.MethodsElectronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission.ResultsCurrent (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97).ConclusionsFormer but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers.ImplicationsPrior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

IntroductionThe initiation of nicotine and tobacco use peaks during adolescence. How adolescent males and females differ based on the acquisition of nicotine use and nicotine-seeking behavior is less understood. Our current studies develop a preclinical intravenous self-administration and reinstatement paradigm in male and female Sprague Dawley rats to evaluate how sex impacts the acquisition of nicotine self-administration and nicotine-seeking, when behavior is initiated during adolescence.Aims and methodsMale and female adolescent rats were food trained under a fixed-ratio one (FR1) schedule of reinforcement and progressively increased to FR5. Animals were implanted with catheters and began nicotine self-administration (0.015 mg/kg/infusion) at FR5 during adolescence on postnatal day 34. Upon reaching stable reinforced responding, animals were tested for progressive ratio (PR) schedules of reinforcement followed by extinction via the removal of drug and associated cues for a minimum of 5 days or until responding was reduced to ≤25% of baseline. Reinstatement testing began for cue only, nicotine only, and a combination of nicotine plus cues using a Latin square design. Animals returned to extinction conditions for 2 days minimum between testing.ResultsNo sex differences were observed for natural rewards, acquisition, and PR schedules of nicotine self-administration, days to extinction, and reinstatement condition.ConclusionsOur findings provide evidence that sex does not impact natural rewards, nicotine reinforcement, reward, and reinstatement, when behavior is initiated during adolescence. Our study offers a feasible approach for assessing nicotine-seeking in male and female Sprague Dawley rats during the unique developmental window of adolescence.ImplicationsThis study demonstrates the impact of nicotine and associated cues in the reinstatement of nicotine-seeking in male and female rats when behavior is initiated during adolescence. Findings support the equivalent impact of nicotine and the nonpharmacological stimuli of cues between male and female adolescent rats that began nicotine self-administration during adolescence.

IntroductionIn response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available.Aims and methodsSixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant).ResultsAverage mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p < .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period.ConclusionAverage puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days.ImplicationsIn an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.

IntroductionInitiation of tobacco products typically occurs in adolescence. Adolescence is a critical period in development where the maturation of brain neurocircuitry is vulnerable to nicotine. Nicotine-containing products and psychostimulants, such as methamphetamine (METH), are often coabused. Rodent studies have shown that nicotine exposure in early adolescence increases subsequent drug intake and reward. Given the exponential increase in e-cigarette use among adolescents, there is a pressing need to understand whether adolescent nicotine exposure impacts concurrent increased METH use. The objective of this study is to evaluate age, sex, and longitudinal effects of nicotine pretreatment on METH reinforcement.Aims and methodsMale and female Sprague-Dawley rats were pretreated with a subchronic, low-dose nicotine (2×, 30 µg/kg/0.1 mL, intravenous) or saline during early adolescence (postnatal days [PN] 28-31) or adulthood (PN 86-89). Following nicotine pretreatment, on PN 32 or PN 90, animals underwent operant intravenous self-administration for METH (20 µg/kg/inf) over a 2-hour period for five consecutive days.ResultsEarly adolescent nicotine exposure enhances intravenous METH self-administration in male, but not female adolescents. Male adult rats self-administer METH over the 5-day testing period, independent of nicotine exposure. In contrast, nicotine exposure increases METH self-administration in female adults during the later sessions of the 5-day testing period.ConclusionsTaken together, our data highlight age- and sex-dependent effects of low dose, subchronic nicotine pretreatment on subsequent intravenous METH self-administration.ImplicationsA majority of polysubstance users begin smoking before the age of 18. Mounting evidence highlights adolescent susceptibility to nicotine exposure on brain and behavior. With the escalation in nicotine-containing products and stimulant use among adolescents, it is important to identify the consequences from adolescent nicotine use, including polysubstance use. Our study provides evidence that adolescent nicotine exposure enhances subsequent METH use, with important sex- and age-dependent effects.

IntroductionAlthough there has been a decrease in the prevalence of tobacco smoking, exposure to nicotine during pregnancy remains a substantial problem worldwide. Further, given the recent escalation in e-cigarette use and legalization of cannabis, it has become essential to understand the effects of nicotine and cannabinoid co-exposure during early developmental stages.Aims and methodsWe systematically examined the effects of nicotine and/or THC prenatal exposure on cognitive behaviors in male and female offspring. Dams were exposed to nicotine vape or vehicle, and oral edible THC or vehicle, throughout pregnancy. Adolescent offspring were then tested in the prepulse inhibition test, novel object recognition task, and novelty suppressed feeding task.ResultsAt birth, pups from mothers exposed to nicotine vape or oral THC exhibited reduced body weight, compared to control pups. Prenatal nicotine vape exposure resulted in a decreased baseline startle reactivity in adolescent male and female rats, and in females, enhanced sensorimotor gating in the prepulse inhibition test. Prenatal nicotine and THC co-exposure resulted in significant deficits in the prepulse inhibition test in males. Deficits in short-term memory were also found in males prenatally exposed to THC, either alone or with nicotine co-exposure, and in females exposed to THC alone. Finally, in males, a modest increase in anxiety-associated behaviors was found with THC or nicotine exposure in the latency to approach a novel palatable food.ConclusionsThese studies demonstrate differential effects of prenatal exposure to e-cigarette nicotine vape and/or edible THC on cognitive function, with differing effects within male and female groups.ImplicationsThese studies demonstrate an impact of nicotine, THC, or co-exposure during early developmental stages in utero on behavioral outcomes in adolescence. These findings have important translational implications given the continued use of nicotine and THC containing products by pregnant women worldwide, which can be applied to support healthcare and policy efforts restricting nicotine and THC use during pregnancy.

IntroductionElectronic nicotine delivery systems (ENDS; ie, vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, their cardiovascular effects are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices, including a new ultrasonic vaping device, impairs endothelial function.Aims and methodsWe measured arterial flow-mediated dilation (FMD) in rats (n = 8/group) exposed to single session of 10 cycles of pulsatile 5-second exposure over 5 minutes to aerosol from e-liquids with and without nicotine generated from a USONICIG ultrasonic vaping device, previous generation e-cigarettes, 5% nicotine JUUL pods (Virginia Tobacco, Mango, Menthol), and an IQOS heated tobacco product; with Marlboro Red cigarette smoke and clean air as controls. We evaluated nicotine absorption and serum nitric oxide levels after exposure, and effects of different nicotine acidifiers on platelet aggregation.ResultsAerosol/smoke from all conditions except air significantly impaired FMD. Serum nicotine varied widely from highest in the IQOS group to lowest in USONICIG and previous generation e-cig groups. Nitric oxide levels were not affected by exposure. Exposure to JUUL and similarly acidified nicotine salt e-liquids did not affect platelet aggregation rate. Despite lack of heating coil, the USONICIG under airflow conditions heated e-liquid to ~77°C.ConclusionsA wide range of ENDS, including multiple types of e-cigarettes with and without nicotine, a heated tobacco product, and an ultrasonic vaping device devoid of heating coil, all impair FMD after a single vaping session comparably to combusted cigarettes.ImplicationsThe need to understand the cardiovascular effects of various ENDS is of timely importance, as we have seen a dramatic increase in the use of these products in recent years, along with the growing assumption among its users that these devices are relatively benign. Our conclusion that a single exposure to aerosol from a wide range of ENDS impairs endothelial function comparably to cigarettes indicates that vaping can cause similar acute vascular functional impairment to smoking and is not a harmless activity.

IntroductionCigarette smoking is strongly associated with the development of cardiovascular disease (CVD). However, evidence is limited as to whether smokeless tobacco (ST) use is associated with CVD.Aims and methodsUsing data from 4347 adults in the Population Assessment of Tobacco and Health Study (2013-2014), we compared geometric mean concentrations of CVD-related harm biomarkers and biomarkers of exposure among exclusive ST users and exclusive cigarette smokers-in relation to recent nicotine exposure-and never tobacco users, adjusting for age, sex, race/ethnicity, income, body mass index, and CVD. Biomarker levels among exclusive ST users who were former established cigarette smokers were compared with exclusive cigarette smokers.ResultsCompared with cigarette smokers, ST users had significantly higher concentrations of total nicotine equivalents (TNE) but lower concentrations of inflammatory (high-sensitivity C-reactive protein, interleukin-6, intercellular adhesion molecule, fibrinogen) and oxidative stress (8-isoprostane) biomarkers (all p < .05). Biomarker levels among ST users were similar to never smokers. ST users who were former cigarette smokers had lower levels of inflammatory and oxidative stress biomarkers and biomarkers of exposure (cadmium, lead, 1-hydroxypyrene, acrylonitrile, and acrolein), compared with cigarettes smokers (p < .05), despite having higher TNE levels (p < .05). Among cigarette smokers, but not among ST users, inflammatory biomarkers and TNE were highly correlated.ConclusionsST use is not associated with increases in biomarkers of CVD-related harm and exposure, compared with never smokers, despite exposure to nicotine at levels higher than those observed among cigarette smokers. These findings support the concept that increases in CVD risk among cigarette smokers is caused primarily by constituents of tobacco smoke other than nicotine.ImplicationsDespite having higher levels of nicotine and compared with exclusive cigarette smokers, exclusive ST users (including those who were former cigarette smokers) had significantly lower concentrations of inflammatory and oxidative stress biomarkers, comparable to levels observed among never tobacco users. These findings suggest that increases in CVD risk among cigarette smokers is caused primarily by tobacco constituents other than nicotine and that switching to ST is likely associated with lower CVD risk.

IntroductionYoung adult never-smokers who vape are at elevated risk of initiating cigarettes, while young adults who smoke often begin vaping to substitute or reduce cigarette use. Reasons underlying different use patterns of tobacco products are not well-understood.Aims and methodsWe conducted 1-on-1 qualitative interviews with young adults (N = 62) who vape in Los Angeles, California from June 2018 to June 2019. Participants were 18-25 years old (79% male; racially/ethnically diverse) and self-reported vaping ≥1x/week. We used a semi-structured interview guide and applied thematic analysis method to analyze data.ResultsYoung adults initiated vaping due to peer socialization and e-liquid flavor novelty. They often reported vaping (after first smoking) due to a belief that e-cigarettes are healthier, social pressure to quit smoking, and convenience of use. Participants reported smoking (after first vaping) when traveling outside of the United States where vaping products were less accessible, and cigarettes were normative. Many of the personal narratives described patterns of dual and cyclical use, which was often attributed to nicotine dependence and cost, or described as dependent upon the current environment (eg, at a party).ConclusionsThe current study characterizes nicotine use trajectories and reasons why young adults vape, and smoke cigarettes. Dual and cyclical use of both e-cigarettes and cigarettes was common; this pattern of use should be considered in policy and prevention work to address nicotine dependence among young people.ImplicationsWe display findings from the current study in a model depicting common trajectories of nicotine use, along with reasons for initiation, transitions between products, and dual/cyclical e-cigarette and combustible cigarette use.

IntroductionIngestion of nicotine by smoking, vaping, or other means elicits various effects including reward, antinociception, and aversion due to irritation, bitter taste, and unpleasant side effects such as nausea and dizziness.Aims and methodsHere we review the sensory effects of nicotine and the underlying neurobiological processes.Results and conclusionsNicotine elicits oral irritation and pain via the activation of neuronal nicotinic acetylcholine receptors (nAChRs) expressed by trigeminal nociceptors. These nociceptors excite neurons in the trigeminal subnucleus caudalis (Vc) and other brainstem regions in a manner that is significantly reduced by the nAChR antagonist mecamylamine. Vc neurons are excited by lingual application of nicotine and exhibit a progressive decline in firing to subsequent applications, consistent with desensitization of peripheral sensory neurons and progressively declining ratings of oral irritation in human psychophysical experiments. Nicotine also elicits a nAChR-mediated bitter taste via excitation of gustatory afferents. Nicotine solutions are avoided even when sweeteners are added. Studies employing oral self-administration have yielded mixed results: Some studies show avoidance of nicotine while others report increased nicotine intake over time, particularly in adolescents and females. Nicotine is consistently reported to increase human pain threshold and tolerance levels. In animal studies, nicotine is antinociceptive when delivered by inhalation of tobacco smoke or systemic infusion, intrathecally, and by intracranial microinjection in the pedunculopontine tegmentum, ventrolateral periaqueductal gray, and rostral ventromedial medulla. The antinociception is thought to be mediated by descending inhibition of spinal nociceptive transmission. Menthol cross-desensitizes nicotine-evoked oral irritation, reducing harshness that may account for its popularity as a flavor additive to tobacco products.ImplicationsNicotine activates brain systems underlying reward and antinociception, but at the same time elicits aversive sensory effects including oral irritation and pain, bitter taste, and other unpleasant side effects mediated largely by nicotinic acetylcholine receptors (nAChRs). This review discusses the competing aversive and antinociceptive effects of nicotine and exposure to tobacco smoke, and the underlying neurobiology. An improved understanding of the interacting effects of nicotine will hopefully inform novel approaches to mitigate nicotine and tobacco use.

IntroductionPrevious studies suggest that young adults who vape nicotine experience difficulty when answering survey items assessing the quantity of vaping. The current study asked young adults who vape to provide suggestions for improving the scientific measurement of vaping.Aims and methodsWe conducted semi-structured qualitative interviews with 62 young adults who vape in Los Angeles, California between June 2018 and June 2019. We analyzed participants' responses to the following question: "What do you think is the best way for us to understand how much people vape?" using thematic content analysis.ResultsWe identified two major themes: (1) challenges stemming from differences between the way researchers query about vaping and how individuals self-monitor vaping frequency, and (2) insights for future measurement of vaping. Participants reported that challenges of accurately quantifying vaping were due to inherently hard-to-answer questions (eg, puffs per day), lack of awareness of or not actively monitoring consumption of vaping products, or because vaping behaviors vary considerably between and within individuals over time, making "on-average" questions challenging. Participants discussed ideas for improving survey measures that could accurately assess vaping quantity, including querying about the type of device used, and frequency of replenishment of nicotine solutions.ConclusionsExisting vaping behavior survey measures may not accurately capture the quantity of vaping as they differ from how (or if) participants track their own vaping consumption patterns. While continued research is needed to optimally refine survey measures on vaping consumption, future measures may better align with vapers' self-monitoring by including questions on device-type and replenishment frequency.ImplicationsThe present study provides insights regarding the variability that exists between vaping quantity measurements utilized by researchers and individuals who consume e-cigarettes. The qualitative data analyzed for this study support previous reports of difficulties faced by vapers when asked questions by researchers related to their vaping behavior. Furthermore, the present findings suggest the direction for the future development of accurate measurements of vaping frequency.

IntroductionThis study examined the predictive relationships between biomarkers of nicotine exposure and 16-item self-reported level of tobacco dependence (TD) and subsequent tobacco use outcomes.Aims and methodsThe Population Assessment of Tobacco and Health (PATH) Study surveyed adult current established tobacco users who provided urine biospecimens at Wave 1 (September 2013-December 2014) and completed the Wave 2 (October 2014-October 2015) interview (n = 6872). Mutually exclusive user groups at Wave 1 included: Cigarette Only, E-cigarette Only, Cigar Only, Hookah Only, Smokeless Tobacco Only, Cigarette Plus E-cigarette, multiple tobacco product users who smoked cigarettes, and multiple tobacco product users who did not smoke cigarettes. Total Nicotine Equivalents (TNE-2) and TD were measured at Wave 1. Approximate one-year outcomes included frequency/quantity used, quitting, and adding/switching to different tobacco products.ResultsFor Cigarette Only smokers and multiple tobacco product users who smoked cigarettes, higher TD and TNE-2 were associated with: a tendency to smoke more, smoking more frequently over time, decreased likelihood of switching away from cigarettes, and decreased probability of quitting after one year. For other product user groups, Wave 1 TD and/or TNE-2 were less consistently related to changes in quantity and frequency of product use, or for adding or switching products, but higher TNE-2 was more consistently predictive of decreased probability of quitting.ConclusionsSelf-reported TD and nicotine exposure assess common and independent aspects of dependence in relation to tobacco use behaviors for cigarette smokers. For other product user groups, nicotine exposure is a more consistent predictor of quitting than self-reported TD.ImplicationsThis study suggests that smoking cigarettes leads to the most coherent pattern of associations consistent with a syndrome of TD. Because cigarettes continue to be prevalent and harmful, efforts to decrease their use may be accelerated via conventional means (eg, smoking cessation interventions and treatments), but also perhaps by decreasing their dependence potential. The implications for noncombustible tobacco products are less clear as the stability of tobacco use patterns that include products such as e-cigarettes continue to evolve. TD, nicotine exposure measures, and consumption could be used in studies that attempt to understand and predict product-specific tobacco use behavioral outcomes.

IntroductionIn 2018, the United States Food and Drug Administration (FDA) required that electronic cigarette (e-cigarette) manufacturers, packagers, importers, distributors, and retailers display an addictive or alternate warning statement on e-cigarette visual advertisements. Few studies have investigated the FDA-mandated and other warnings on social media. This study examined the prevalence and content of warning statements in e-cigarette-related YouTube videos.MethodsIn 2019, The Virginia Commonwealth University Center for the Study of Tobacco Products conducted bi-monthly (February-June) YouTube searches by relevance and view count to identify e-cigarette-related videos. Overall, 178 videos met the inclusion criteria. Staff coded each video for the presence of a visual/verbal warning statement, warning statement type (eg, FDA-mandated, addiction/tobacco, safety/toxic exposure, health effects), sponsorship, and tobacco product characteristics. A data extraction tool collected the video URL, title, upload date, and number of views, likes/dislikes, and comments.ResultsOnly 5.1% of videos contained FDA-mandated and 21.9% contained non-mandated warnings. All videos with FDA-mandated and 46.2% of non-mandated warnings were represented visually. Only 13.1% of industry-sponsored videos uploaded after the mandate effective date had an FDA-mandated warning statement and videos with FDA-mandated and non-mandated (v. no) warnings had significantly fewer views, likes, dislikes, and comments. Among all non-mandated warnings, 31.3% featured an addiction/tobacco, 18.8% a safety/toxic exposure, and 37.5% a health effects warning.ConclusionsThe prevalence of FDA-mandated warning statements in e-cigarette related YouTube videos was low. FDA enforcement of the warning statement mandate on YouTube could increase the public's understanding of the addictive nature of nicotine in e-cigarettes.ImplicationsThe FDA has the authority to regulate the advertisement and promotion of e-cigarettes on the Internet. These data can inform future FDA requirements related to the language content and visual representation of addiction/tobacco, safety/exposure, and health effects warning statements that appear in YouTube videos and other visual social media popular among young people. Such data would help consumers make informed decisions about purchasing e-cigarette products, using e-cigarettes, and avoiding unintentional harm related to e-cigarettes. In addition, these data may help social media platforms make decisions on whether they will prohibit advertisements that promote or facilitate the sale of tobacco products.

IntroductionCalifornia implemented multiple strategies, such as a Tobacco 21 law and compliance checks, to reduce high rates of youth e-cigarette use. However, the prevalence of use among underage youth and young adults continues rising. Little is known about how underage individuals obtain e-cigarettes.Aims and methodsWe conducted structured qualitative interviews with 61 young adult (18-25 years old) vapers in the Los Angeles, CA area between June 2018 and June 2019. Interviews were comprehensive and designed to elicit information on participants' thoughts, feelings, and experiences related to vaping. We queried participants on where and how they obtained vaping products, and participants discussed their experiences accessing products while under the legal age for sale. Directed content analysis was used to analyze interviews.ResultsFour concepts emerged: (1) early experimentation of e-cigarettes with peers often occurred in a school setting, (2) continued use of e-cigarettes commonly obtained through peer sales, (3) inconsistent implementation of age restrictions at in-person retailers, and (4) at online retailers. Participants had peers purchase products on their behalf and frequented in-person and online retailers with few to no age verification processes. Few participants faced challenges when purchasing products from retailers.ConclusionsThe current study's findings offer insight into where and how underage individuals obtain vaping products despite restrictions to prevent them from doing so. Participant accounts of mixed ease of underage purchasing in-person and online suggest retailer education is needed, along with additional research to inform more effective policies to reduce underage access to vaping products.ImplicationsDespite legal age restrictions, e-cigarettes remain accessible to underage individuals, but specific strategies that underage youth utilize to evade legal age restrictions are largely unknown. We found that participants often accessed vaping products for the first time at school. Sales between peers were common, and participants also reported frequenting in-person retailers that inconsistently enforced age restrictions. Many participants reported little to no age verification online, though some believed online age verification measures were increasingly difficult to surpass. Knowledge of strategies underage youth utilize to access e-cigarettes can inform enforcement efforts.

IntroductionSimple silicone wristbands (WB) hold promise for exposure assessment in children. We previously reported strong correlations between nicotine in WB worn by children and urinary cotinine (UC). Here, we investigated differences in WB chemical concentrations among children exposed to secondhand smoke from conventional cigarettes (CC) or secondhand vapor from electronic cigarettes (EC), and children living with nonusers of either product (NS).MethodsChildren (n = 53) wore three WB and a passive nicotine air sampler for 7 days and one WB for 2 days, and gave a urine sample on day 7. Caregivers reported daily exposures during the 7-day period. We determined nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) concentrations in WB, nicotine in air samplers, and UC through isotope-dilution liquid chromatography with triple-quadrupole mass spectrometry.ResultsNicotine and cotinine levels in WB in children differentiated between groups of children recruited into NS, EC exposed, and CC exposed groups in a similar manner to UC. WB levels were significantly higher in the CC group (WB nicotine median 233.8 ng/g silicone, UC median 3.6 ng/mL, n = 15) than the EC group (WB nicotine median: 28.9 ng/g, UC 0.5 ng/mL, n = 19), and both CC and EC group levels were higher than the NS group (WB nicotine median: 3.7 ng/g, UC 0.1 ng/mL, n = 19). TSNAs, including the known carcinogen NNK, were detected in 39% of WB.ConclusionsSilicone WB show promise for sensitive detection of exposure to tobacco-related contaminants from traditional and electronic cigarettes and have potential for tobacco control efforts.ImplicationsSilicone WB worn by children can absorb nicotine, cotinine, and tobacco-specific nitrosamines, and amounts of these compounds are closely related to the child's urinary cotinine. Levels of tobacco-specific compounds in the silicone WB can distinguish patterns of children's exposure to secondhand smoke and e-cigarette vapor. Silicone WB are simple to use and acceptable to children and, therefore, may be useful for tobacco control activities such as parental awareness and behavior change, and effects of smoke-free policy implementation.

IntroductionToxic tobacco smoke residue, also known as thirdhand smoke (THS), can persist in indoor environments long after tobacco has been smoked. This study examined the effects of different cleaning methods on nicotine in dust and on surfaces.Aims and methodsParticipants had strict indoor home smoking bans and were randomly assigned to: dry/damp cleaning followed by wet cleaning 1 month later (N = 10), wet cleaning followed by dry/damp cleaning (N = 10) 1 month later, and dry/damp and wet cleaning applied the same day (N = 28). Nicotine on surfaces and in dust served as markers of THS and were measured before, immediately after, and 3 months after the cleaning, using liquid chromatography with triple quadrupole mass spectrometry (LC-MS/MS).ResultsOver a 4-month period prior to cleaning, surface nicotine levels remained unchanged (GeoMean change: -11% to +8%; repeated measures r = .94; p < .001). Used separately, dry/damp and wet cleaning methods showed limited benefits. When applied in combination, however, we observed significantly reduced nicotine on surfaces and in dust. Compared with baseline, GeoMean surface nicotine was 43% lower immediately after (z = -3.73, p < .001) and 53% lower 3 months later (z = -3.96, p < .001). GeoMean dust nicotine loading declined by 60% immediately after (z = -3.55, p < .001) and then increased 3 months later to precleaning levels (z = -1.18, p = .237).ConclusionsCleaning interventions reduced but did not permanently remove nicotine in dust and on surfaces. Cleaning efforts for THS need to address persistent pollutant reservoirs and replenishment of reservoirs from new tobacco smoke intrusion. THS contamination in low-income homes may contribute to health disparities, particularly in children.ImplicationsAdministered sequentially or simultaneously, the tested cleaning protocols reduced nicotine on surfaces by ~50% immediately after and 3 months after the cleaning. Nicotine dust loading was reduced by ~60% immediately after cleaning, but it then rebounded to precleaning levels 3 months later. Cleaning protocols were unable to completely remove THS, and pollutants in dust were replenished from remaining pollutant reservoirs or new secondhand smoke intrusion. To achieve better outcomes, cleaning protocols should be systematically repeated to remove newly accumulated pollutants. New secondhand smoke intrusions need to be prevented, and remaining THS reservoirs should be identified, cleaned, or removed to prevent pollutants from these reservoirs to accumulate in dust and on surfaces.

IntroductionThirdhand smoke (THS) is ultrafine particulate matter and residue resulting from tobacco combustion, with implications for health-related harm (eg, impaired wound healing), particularly among hospitalized infants. Project aims were to characterize nicotine (THS proxy) transported on neonatal intensive care unit (NICU) visitors and deposited on bedside furniture, as well as infant exposure.MethodsCross-sectional data were collected from participants in a metropolitan NICU. Participants completed a survey and carbon monoxide breath sample, and 41.9% (n = 88) of participants (n = 210) were randomly selected for finger-nicotine wipes during a study phase when all bedside visitors were screened for nicotine use and finger-nicotine levels. During an overlapping study phase, 80 mother-infant dyads consented to bedside furniture-nicotine wipes and an infant urine sample (for cotinine analyses).ResultsMost nonstaff visitors' fingers had nicotine above the limit of quantification (>LOQ; 61.9%). Almost all bedside furniture surfaces (93.8%) and infant cotinine measures (93.6%) had values >LOQ, regardless of household nicotine use. Participants who reported using (or lived with others who used) nicotine had greater furniture-nicotine contamination (Mdn = 0.6 [interquartile range, IQR = 0.2-1.6] µg/m2) and higher infant cotinine (Mdn = 0.09 [IQR = 0.04-0.25] ng/mL) compared to participants who reported no household-member nicotine use (Mdn = 0.5 [IQR = 0.2-0.7] µg/m2; Mdn = 0.04 [IQR = 0.03-0.07] ng/mL, respectively). Bayesian univariate regressions supported hypotheses that increased nicotine use/exposure correlated with greater nicotine contamination (on fingers/furniture) and infant THS exposure.ConclusionsPotential furniture-contamination pathways and infant-exposure routes (eg, dermal) during NICU hospitalization were identified, despite hospital prohibitions on tobacco/nicotine use. This work highlights the surreptitious spread of nicotine and potential THS-related health risks to vulnerable infants during critical stages of development.ImplicationsTHS contamination is underexplored in medical settings. Infants who were cared for in the NICU are vulnerable to health risks from THS exposure. This study demonstrated that 62% of nonstaff NICU visitors transport nicotine on their fingers to the NICU. Over 90% of NICU (bedside) furniture was contaminated with nicotine, regardless of visitors' reported household-member nicotine use or nonuse. Over 90% of infants had detectable levels of urinary cotinine during NICU hospitalizations. Results justify further research to better protect infants from unintended THS exposure while hospitalized.

IntroductionWe illustrate the differential impact of common analysis approaches to handling urinary creatinine, a measure for urine dilution, on relationships between race, gender, and biomarkers of exposure measured in spot urine.MethodsIn smokers, spot urine levels of total nicotine equivalents (TNE, sum of total nicotine, total cotinine, and total 3'-hydroxycotinine) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) overall and per cigarette were examined. Relationships between race (African Americans [AA] n = 373, Whites n = 758) or gender (males n = 629, females n = 502) and TNE or NNAL were examined using the following approaches to handling creatinine: (1) unadjusted/unstandardized; (2) standardization; (3) adjustment as a covariate. Significance was considered at p < .05.ResultsCreatinine was higher in AA versus Whites (1.19 vs. 0.96 mg/mL; p < .0001) and in males versus females (1.21 vs. 0.84 mg/mL; p < .0001). Independent of how creatinine was handled, TNE was lower among AA than Whites (TNE ratios AA vs. Whites: 0.67-0.84; p's < .05). Unadjusted TNE per cigarette was higher among AA versus Whites (ratio 1.12; p = .0411); however, the relationship flipped with standardization (ratio 0.90; p = .0360) and adjustment (ratio 0.95; p = .3165). Regarding gender, unadjusted TNE was higher among males versus females (ratio 1.13; p = .0063), but the relationship flipped with standardization (ratio 0.79; p < .0001) or adjustment (ratio 0.89; p = .0018). Unadjusted TNE per cigarette did not differ across gender (ratio 0.98; p = .6591), but lower levels were found in males versus females with standardization (ratio 0.68; p < .0001) and adjustment (ratio 0.74; p < .0001). NNAL displayed similar patterns.ConclusionsRelationships between race, gender, and spot urine levels of biomarkers of exposure can vary greatly based on how creatinine is handled in analyses.ImplicationsLack of appropriate methods can lead to discrepancies across reports on variability of urinary biomarkers by race and gender. We recommend that for any analyses of biomarkers of exposure measure in spot urine samples across race, gender, or other population subgroups that differ in urinary creatinine levels, sensitivity analyses comparing the different methods for handling urinary creatinine should be conducted. If methods result in discrepant findings, this should be clearly noted and discussed.

IntroductionApproximately the same percentage of male high school students in the United States currently uses conventional smokeless tobacco as smokes cigarettes, resulting in toxin exposure.MethodsThis study assessed tobacco product use (smokeless, combustible, and electronic cigarettes) and nicotine and carcinogen exposures in a sample of 594 male rural high school baseball players-a population traditionally at risk for smokeless tobacco use. Salivary specimens were assayed for cotinine (a biomarker of nicotine exposure) and urine specimens for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a biomarker of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) using liquid chromatography-tandem mass spectrometry.ResultsThe prevalence of past 30-day use of any tobacco product was 29%. Past 7-day smokeless tobacco use (prevalence: 13%) was associated with the highest levels of cotinine and NNAL observed in the sample, whether smokeless tobacco was used exclusively (geometric means: cotinine 11.1 ng/mL; NNAL 31.9 pg/mg-creatinine) or in combination with combustible products (geometric means: cotinine 31.6 ng/mL; NNAL 50.0 pg/mg creatinine). Cotinine and NNAL levels were incrementally higher in each increasing category of smokeless tobacco use frequency. However, observed levels were lower than previously reported for adults, likely reflecting less smokeless use per day among adolescents.ConclusionsBased on these biomarker observations, adolescents who use conventional smokeless tobacco products are exposed to substantial levels of nicotine and NNK. Although exposed to lower levels than adult smokeless users, the findings are concerning given the young age of the sample and tendency for smokeless tobacco users to increase use intensity over time.ImplicationsThis study demonstrates that adolescents using smokeless tobacco are exposed to levels of nicotine and NNK that increase with use frequency and that exceed exposures among peers using other tobacco products. Youth smokeless tobacco use in the United States has not declined along with youth smoking prevalence, giving greater importance to this health concern. To reduce youth (and adult) exposures, needed actions include effective smokeless tobacco use prevention, potentially in combination with reducing the levels of harmful and potentially harmful chemicals in smokeless tobacco products currently popular among adolescents.

IntroductionThe rate of nicotine metabolism, estimated by the nicotine metabolite ratio (NMR), is an important determinant of tobacco dependence. This study investigated the effect of NMR on smoking behavior due to nicotine reinforcement during ad libitum smoking.Aims and methodsAs part of a larger study, participants were stratified based on saliva NMR as fast and slow metabolizers. After smoking a cigarette and measuring nicotine blood concentrations, participants smoked as desired over a 90-minute period. Analysis included time to first cigarette, total number of cigarettes, total number of puffs, and weight of tobacco consumed.ResultsSixty-one (48%) participants were fast metabolizers and 66 (52%) slow metabolizers by NMR. No significant differences were found regarding the smoking topography variables by NMR. Normal metabolizers by genotype (n = 79) had a shorter time to first cigarette than reduced metabolizers (n = 39; p = .032). Blacks smoked fewer cigarettes (p = .008) and took fewer total puffs (p = .002) compared with Whites. Among Whites, fast metabolizers by NMR had a shorter time to first cigarette compared with slow metabolizers (p = .014). Among fast metabolizers, Whites had, compared with Blacks, shorter latency to first cigarette (p = .003) and higher number of total puffs (p = .014) and cigarettes smoked (p = .014). Baseline cigarettes per day and nicotine elimination half-life significantly predicted topography outcomes.ConclusionsSaliva NMR did not predict cigarette reinforcement during a relatively brief period of ad libitum smoking. Differences were seen by race, with White fast metabolizers by NMR having shorter time to first cigarettes compared with slow metabolizers.ImplicationsAfter a 90-minute period of nicotine abstinence, NMR was not significantly associated with smoking reinforcement. Slow and fast metabolizers had similar time to first cigarette, number of cigarettes smoked, total number of puffs, and tobacco consumed; however, within-race differences show that within Whites, fast metabolizers had a faster time to first cigarette than slow metabolizers.

IntroductionDuring adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic "spice" cannabinoid agonists.Aims and methodsThe current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days.ResultsWe found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence.ConclusionsThese data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood.ImplicationsThese studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic "spice" cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.

INTRODUCTION: We describe the development and pilot testing of the experimental tobacco and nicotine product marketplace (ETM)-a method for studying tobacco and nicotine product (TNP) choices and use behavior in a standardized way. AIMS AND METHODS: The ETM resembles an online store populated with TNPs. Surveillance activities and data from a US representative survey and consumer reports were used to determine the most popular TNPs for inclusion in the ETM. Standardized information and videos demonstrating how to use the TNPs were provided. To test the feasibility of using the ETM, smokers (n = 119) underwent monitoring of usual brand cigarette smoking and other TNP use (Baseline Phase) followed by access to the ETM (ETM Phase) that included their usual brand cigarettes, e-cigarettes, moist snuff, snus, and nicotine replacement therapy. During the ETM Phase, participants were provided points based on their baseline TNP consumption to exchange for TNPs in the ETM. Participants were advised to exchange points for enough TNPs to last until their next visit and to refrain from using TNPs not obtained in the ETM. A subset of the participants (n = 62) completed a survey on their experience with the ETM. RESULTS: The majority of the participants stated they were comfortable with navigating the ETM (97%), it was easy to determine product characteristics (89%), and they were satisfied with the products included in the marketplace (85%). CONCLUSIONS: The ETM was well received by the vast majority of the participants and can be utilized by researchers to investigate a variety of TNP policy and regulatory science research questions. IMPLICATIONS: Patterns of TNP use are complex due to greater availability, marketing, and promotion of a diverse array of TNPs. Innovative methods are needed to experimentally study TNP choices and patterns. Through describing the development of the ETM, we provide researchers with a tool that can be readily adapted to studying a variety of phenomena challenging public health.

IntroductionDual use of electronic cigarettes (e-cigarettes) and combustible cigarettes is a major public health issue. It is generally accepted that exclusive e-cigarette use is less harmful than exclusive combustible cigarette use, but most e-cigarette users continue to smoke combustible cigarettes as well. To what extent the use of e-cigarettes reduces harm in people who continue to smoke combustible cigarettes has been debated. The aim of this study was to explore the utility of biomarkers as measures of dual use.MethodsIn two human studies of participants who used e-cigarettes only or both combustible cigarettes and e-cigarettes, we measured urine concentrations of the metabolites of nicotine (total nicotine equivalents) as well as two biomarkers of tobacco exposure: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen metabolite, and nicotelline, a tobacco alkaloid not found in significant concentrations in e-cigarette products.ResultsThe presence of nicotine metabolites indicates either e-cigarette or combustible cigarette use. Nicotelline (half-life of 2-3 hours) indicates recent combustible cigarette use and NNAL (half-life of 10 days or more), indicates combustible cigarette use occurring within several weeks prior to sample collection.ConclusionsNicotelline and NNAL are useful biomarkers for combustible tobacco use in users e-cigarettes. The application of these biomarkers provides a tool to help assess whether, or to what extent, dual use of e-cigarettes and combustible cigarettes reduces harm compared to sole use of combustible cigarettes. These biomarkers can also verify exclusive use of e-cigarettes over short (24 hour) or long (several week) time periods.ImplicationsTo what extent dual use of e-cigarettes and combustible cigarettes reduce harm compared to smoking combustible cigarettes only is of considerable public health interest. We show that the levels of the minor tobacco alkaloid nicotelline and the nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are extremely low in electronic cigarette fluids. The urine biomarkers nicotelline and the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are indicative of cigarette smoking and can be used to assess recent and past smoking in dual users.

BackgroundThe changing prevalence and patterns of tobacco use, the advent of novel nicotine delivery devices, and the development of new biomarkers prompted an update of the 2002 Society for Research on Nicotine and Tobacco (SRNT) report on whether and how to apply biomarker verification for tobacco use and abstinence.MethodsThe SRNT Treatment Research Network convened a group of investigators with expertise in tobacco biomarkers to update the recommendations of the 2002 SNRT Biochemical Verification Report.ResultsBiochemical verification of tobacco use and abstinence increases scientific rigor and is recommended in clinical trials of smoking cessation, when feasible. Sources, appropriate biospecimens, cutpoints, time of detection windows and analytic methods for carbon monoxide, cotinine (including over the counter tests), total nicotine equivalents, minor tobacco alkaloids, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol are reviewed, as well as biochemical approaches to distinguishing cigarette smoking from use of electronic nicotine delivery devices (ENDS).ConclusionsRecommendations are provided for whether and how to use biochemical verification of tobacco use and abstinence. Guidelines are provided on which biomarkers to use, which biospecimens to use, optimal cutpoints, time windows to detection, and methodology for biochemical verifications. Use of combinations of biomarkers is recommended for assessment of ENDS use.ImplicationsBiochemical verification increases scientific rigor, but there are drawbacks that need to be assessed to determine whether the benefits of biochemical verification outweigh the costs, including the cost of the assays, the feasibility of sample collection, the ability to draw clear conclusions based on the duration of abstinence, and the variability of the assay within the study population. This paper provides updated recommendations from the 2002 SRNT report on whether and how to use biochemical markers in determining tobacco use and abstinence.

IntroductionMany electronic cigarette manufacturers have begun offering liquids containing "nicotine salts," which are formed when an acid is mixed in a solution with free-base nicotine. Type of salt could play a significant role in the abuse liability of electronic cigarette liquids. As a first step to understanding nicotine salts, this study sought to identify the types of acids present in 23 commercially available electronic cigarette liquids.Aims and methodsTwenty-three electronic cigarette liquids advertised as containing nicotine salts were purchased for analysis. These liquids were tested for the presence of 11 different organic acids that were deemed likely to be used in a nicotine salt formulation. Liquids were analyzed using a combination of liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry methods, then compared to authentic acid standards for identification.ResultsSix of the 11 possible acids were identified in the liquids, from most to least common: lactic, benzoic, levulinic, salicyclic, malic, and tartaric acid. Acid(s) could not be identified in one of the liquids. Though most liquids contained only one type, three of the liquids contained multiple acids.ConclusionsThese data demonstrate that several types of salts/acids are currently being used in electronic cigarette liquids. The type and concentration of salt(s) used in these liquids may differentially alter sensations in the throat and upper airway, and overall pharmacology of the aerosols by altering liquid pH and from flavor and sensory characteristics of the acids themselves.ImplicationsThis study demonstrates that at least six different types of acids are being used to create the nicotine salts in electronic cigarette liquids, with the acids lactic, benzoic, and levulinic being the most frequently identified. Identification of these acids can serve as the foundation for future research to determine if type of nicotine salt alters pharmacological and toxicological effects of electronic cigarettes.

IntroductionWe describe the development and pilot testing of the experimental tobacco and nicotine product marketplace (ETM)-a method for studying tobacco and nicotine product (TNP) choices and use behavior in a standardized way.Aims and methodsThe ETM resembles an online store populated with TNPs. Surveillance activities and data from a US representative survey and consumer reports were used to determine the most popular TNPs for inclusion in the ETM. Standardized information and videos demonstrating how to use the TNPs were provided. To test the feasibility of using the ETM, smokers (n = 119) underwent monitoring of usual brand cigarette smoking and other TNP use (Baseline Phase) followed by access to the ETM (ETM Phase) that included their usual brand cigarettes, e-cigarettes, moist snuff, snus, and nicotine replacement therapy. During the ETM Phase, participants were provided points based on their baseline TNP consumption to exchange for TNPs in the ETM. Participants were advised to exchange points for enough TNPs to last until their next visit and to refrain from using TNPs not obtained in the ETM. A subset of the participants (n = 62) completed a survey on their experience with the ETM.ResultsThe majority of the participants stated they were comfortable with navigating the ETM (97%), it was easy to determine product characteristics (89%), and they were satisfied with the products included in the marketplace (85%).ConclusionsThe ETM was well received by the vast majority of the participants and can be utilized by researchers to investigate a variety of TNP policy and regulatory science research questions.ImplicationsPatterns of TNP use are complex due to greater availability, marketing, and promotion of a diverse array of TNPs. Innovative methods are needed to experimentally study TNP choices and patterns. Through describing the development of the ETM, we provide researchers with a tool that can be readily adapted to studying a variety of phenomena challenging public health.

IntroductionAccurate measurement of nicotine exposure from cigarette smoke is important in studying disease risk and level of dependence. Urine total nicotine equivalents, the molar sum of nicotine and six metabolites (NE7), accounts for more than 90% of a nicotine dose and is independent of individual metabolic differences. However, measuring NE7 is technically difficult and costly. We compared NE7, the gold standard of nicotine intake, with different combinations of fewer urinary nicotine metabolites. We also examined the impact of individual differences in nicotine metabolic rate, sex, and race on strength of association with NE7.MethodsUrine samples from 796 daily smokers, who participated across five clinical studies, were assayed for nicotine and/or metabolites. Associations with NE7 were assessed by regression and Bland-Altman analyses.ResultsOverall, the molar sum of urine [cotinine + 3'-hydroxycotinine (3HC)] (NE2) and [nicotine + 
cotinine + 3HC] (NE3) were strongly correlated with NE7 (r = .97 and .99, respectively). However, in slow metabolizers NE2 was less predictive of NE7, whereas NE3 was equally robust. Urine total cotinine was also strongly correlated with NE7 (r = .87).ConclusionsUrine NE3 is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, whereas NE2 is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies.ImplicationsThe molar sum of urine total nicotine, cotinine and 3HC (NE3) is a robust biomarker of daily nicotine intake, independently of individual metabolic differences, and performs as well as measuring seven nicotine metabolites (NE7). The sum of cotinine and 3HC (NE2) is less accurate in slow metabolizers. Our findings inform the selection of more rigorous and cost-effective measures to assess nicotine exposure in tobacco research studies.

The available research on switching from normal nicotine to very low nicotine content cigarettes shows minimal evidence of compensatory smoking. Mathematical estimations suggest that substantial compensation after switching to very low nicotine cigarettes would be impossible. It is likely that smokers who are unable to tolerate the extent of proposed nicotine reduction would switch to other sources of nicotine, rather than try to compensate by smoking more very low nicotine content cigarettes more intensely.

IntroductionBecause 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy.MethodsIn a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence.ResultsAt baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (-6.4 vs. -9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (-4.5 vs. -7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition.ConclusionsAlthough menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers.ImplicationsResults of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes.

Introduction:Sugars are major constituents and additives in traditional tobacco products, but little is known about their content or related toxins (formaldehyde, acetaldehyde, and acrolein) in electronic cigarette (e-cigarette) liquids. This study quantified levels of sugars and aldehydes in e-cigarette liquids across brands, flavors, and nicotine concentrations (n = 66). Methods:Unheated e-cigarette liquids were analyzed using liquid chromatography mass spectrometry and enzymatic test kits. Generalized linear models, Fisher's exact test, and Pearson's correlation coefficient assessed sugar, aldehyde, and nicotine concentration associations. Results:Glucose, fructose and sucrose levels exceeded the limits of quantification in 22%, 53% and 53% of the samples. Sucrose levels were significantly higher than glucose [χ2(1) = 85.9, p < .0001] and fructose [χ2(1) = 10.6, p = .001] levels. Formaldehyde, acetaldehyde, and acrolein levels exceeded the limits of quantification in 72%, 84%, and 75% of the samples. Acetaldehyde levels were significantly higher than formaldehyde [χ2(1) = 11.7, p = .0006] and acrolein [χ2(1) = 119.5, p < .0001] levels. Differences between nicotine-based and zero-nicotine labeled e-cigarette liquids were not statistically significant for sugars or aldehydes. We found significant correlations between formaldehyde and fructose (-0.22, p = .004) and sucrose (-0.25, p = .002) and acrolein and fructose (-0.26, p = .0006) and sucrose (-0.21, p = .0006). There were no significant correlations between acetaldehyde and any of the sugars or any of the aldehydes and glucose. Conclusions:Sugars and related aldehydes were identified in unheated e-cigarette liquids and their composition may influence experimentation in naïve users and their potential toxicity. Implications:The data can inform the regulation of specific flavor constituents in tobacco products as a strategy to protect young people from using e-cigarettes, while balancing FDA's interest in how these emerging products could potentially benefit adult smokers who are seeking to safely quit cigarette smoking. The data can also be used to educate consumers about ingredients in products that may contain nicotine and inform future FDA regulatory policies related to product standards and accurate and comprehensible labeling of e-cigarette liquids.

IntroductionPrior 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.MethodsResearch 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.ResultsData 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.ConclusionsMost 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.ImplicationsThese 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.

IntroductionScientific discoveries over the past few decades have provided significant insight into the abuse liability and negative health consequences associated with tobacco and nicotine-containing products. While many of these advances have led to the development of policies and laws that regulate access to and formulations of these products, further research is critical to guide future regulatory efforts, especially as novel nicotine-containing products are introduced and selectively marketed to vulnerable populations.DiscussionIn this narrative review, we provide an overview of the scientific findings that have impacted regulatory policy and discuss considerations for further translation of science into policy decisions. We propose that open, bidirectional communication between scientists and policy makers is essential to develop transformative preventive- and intervention-focused policies and programs to reduce appeal, abuse liability, and toxicity of the products.ConclusionsThrough these types of interactions, collaborative efforts to inform and modify policy have the potential to significantly decrease the use of tobacco and alternative nicotine products and thus enhance health outcomes for individuals.ImplicationsThis work addresses current topics in the nicotine and tobacco research field to emphasize the importance of basic science research and provide examples of how it can be utilized to inform public policy. In addition to relaying current thoughts on the topic from experts in the field, the article encourages continued efforts and communication between basic scientists and policy officials.

BackgroundThere is considerable debate about the benefits and risks of electronic cigarettes (ECs). To better understand the risk-benefit ratio of ECs, more information is needed about net nicotine consumption and toxicant exposure of cigarette smokers switching to ECs.MethodsForty cigarette smokers (≥1 year of smoking) interested in switching to ECs but not necessarily quitting smoking were enrolled in a 4-week observational study and provided an e-Go C non-variable battery and refillable atomizers and choice of eight flavors in 12 or 24 mg nicotine dosage. Measurement of urinary cotinine (metabolite of nicotine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a pulmonary carcinogen), and eight volatile organic compounds (VOCs) that are toxic tobacco smoke constituents was conducted at baseline and week 4.ResultsAll participants with follow-up data (92.5%) reported using the study EC. Of the 40 smokers, 16 reported no cigarettes at week 2 (40%) and six continued to report no cigarettes at week 4 (15%). Change in nicotine intake over the 4 weeks was non-significant (p = .90). Carbon monoxide (p < .001), NNAL (p < .01) and metabolites of benzene (p < .01) and acrylonitrile (p = .001) were significantly decreased in the study sample. Smokers switching exclusively to ECs for at least half of the study period demonstrated significant reductions in metabolites of ethylene oxide (p = .03) and acrylamide (p < .01).ConclusionSmokers using ECs over 4 weeks maintained cotinine levels and experienced significant reductions in carbon monoxide, NNAL, and two out of eight measured VOC metabolites. Those who switched exclusively to ECs for at least half of the study period significantly reduced two additional VOCs.ImplicationsThis study extends current literature by measuring change in smoking dependence and disease-associated biomarkers, NNAL and a panel of eight common VOCs that are toxic tobacco smoke constituents in smokers who switch to ECs. The findings support the idea of harm reduction, however some levels of toxicant exposure are still of clinical concern, particularly for dual users. Extrapolation of these results must be careful to separate the different toxic exposure results for exclusive switchers versus dual cigarette + EC users, and not to equate harm reduction with the idea that using ECs is harmless.

IntroductionCharacterization of aerosols generated by electronic cigarettes (e-cigarettes) is one method used to evaluate the safety of e-cigarettes. While some researchers have modified smoking machines for e-cigarette aerosol generation, these machines are either not readily available, not automated for e-cigarette testing or have not been adequately described. The objective of this study was to build an e-cigarette vaping machine that can be used to test, under standard conditions, e-liquid aerosolization and nicotine and toxicant delivery.MethodsThe vaping machine was assembled from commercially available parts, including a puff controller, vacuum pump, power supply, switch to control current flow to the atomizer, three-way value to direct air flow to the atomizer, and three gas dispersion tubes for aerosol trapping. To validate and illustrate its use, the variation in aerosol generation was assessed within and between KangerTech Mini ProTank 3 clearomizers, and the effect of voltage on aerosolization and toxic aldehyde generation were assessed.ResultsWhen using one ProTank 3 clearomizer and different e-liquid flavors, the coefficient of variation (CV) of aerosol generated ranged between 11.5% and 19.3%. The variation in aerosol generated between ProTank 3 clearomizers with different e-liquid flavors and voltage settings ranged between 8.3% and 16.3% CV. Aerosol generation increased linearly at 3-6V across e-liquids and clearomizer brands. Acetaldehyde, acrolein, and formaldehyde generation increased markedly at voltages at or above 5V.ConclusionThe vaping machine that we describe reproducibly aerosolizes e-liquids from e-cigarette atomizers under controlled conditions and is useful for testing of nicotine and toxicant delivery.ImplicationsThis study describes an electronic cigarette vaping machine that was assembled from commercially available parts. The vaping machine can be replicated by researchers and used under standard conditions to generate e-cigarette aerosols and characterize nicotine and toxicant delivery.

IntroductionThe ratio of trans 3'-hydroxycotinine (3HC) to cotinine (nicotine metabolite ratio [NMR]) is a biomarker of the rate of nicotine metabolism, with higher NMR indicating faster metabolism. Higher NMR has been found to be associated with higher daily cigarette consumption and less success stopping smoking in cessation trials. This study examines differences in NMR among population-based samples of smokers in the five countries and explores the relationship between NMR and smoking abstinence.MethodsParticipants (N = 874) provided saliva samples during International Tobacco Control (ITC) surveys in the United States, United Kingdom, Mauritius, Mexico, and Thailand conducted in 2010/2011 with follow-up surveys in 2012/2013. When all samples were received, they were sent to a common laboratory for analysis using liquid chromatography and tandem mass spectroscopy.ResultsThere was significant variation in NMR across countries (F = 15.49, p < .001). Those who reported smoking at follow-up had a mean NMR of 0.32, compared to a mean NMR of 0.42 in participants who reported that they had stopped (F = 8.93; p = .003). Higher mean NMR values were also associated with longer quit duration (p = .007). There was no substantial difference in NMR between current smokers who made a failed quit attempt and those who made no attempt-both had significantly lower NMR compared to those who quit and remained abstinent. Smokers with a higher NMR were more likely to report that they stopped smoking compared to those with a lower NMR (odds ratio = 2.67; 95% confidence interval: 1.25 to 5.68).ConclusionsThese results suggest faster nicotine metabolizers may be less likely to relapse following a quit attempt. This finding differs from results of clinical trials testing stop smoking medications, where slower metabolizers have been found to be more likely to maintain abstinence from smoking.ImplicationsResults of this study suggest faster nicotine metabolizers may be less likely to relapse following a quit attempt. This finding differs from results of clinical trials testing stop smoking medications, where slower metabolizers have been found to be more likely to maintain abstinence from smoking.

IntroductionElectronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants.MethodsWe measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance.ResultsIn total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2.ConclusionsAfter switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced.ImplicationsTo our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device.

IntroductionThe majority of people with schizophrenia have a diagnosis of tobacco dependence during their lifetime. A major obstacle to reducing the burden of cigarette smoking in this population is that these smokers have lower quit rates when undergoing standard treatment compared to smokers with no mental illness. We sought to determine if combination extended treatment (COMB-EXT) and home visits (HV) would lead to improved outcomes in smokers with schizophrenia.MethodsThirty-four cigarette smokers with schizophrenia completed either COMB-EXT with HV, COMB-EXT without HV, or treatment as usual (TAU) (random assignment). COMB-EXT consisted of group cognitive-behavioral therapy (CBT), bupropion, nicotine patch, and nicotine lozenge, which were initiated within 2 weeks and continued for 26 weekly visits. HV consisted of biweekly visits to the home with assessment of secondhand smoke (SHS) exposure and brief behavioral therapy with participants and others in the home environment. TAU consisted of group CBT plus serial single or combination medication trials as per standard care.ResultsSmokers with schizophrenia who received COMB-EXT (with or without HV) had greater reductions in cigarettes per day than those treated with TAU (both ps < .01). In addition, 7-day point prevalence abstinence rates for the three groups were 45%, 20%, and 8%, respectively, which was significantly higher for COMB-EXT plus HV than TAU (χ2(1) = 4.8, p = .03). Groups did not differ significantly in the number of adverse events, and HV were easily scheduled.ConclusionCOMB-EXT improves outcomes for smokers with schizophrenia. HV appeared to provide additional benefit for smoking cessation in this treatment-resistant population.ImplicationsThe clear benefit found here of rapidly initiated, combination, extended treatment over TAU suggests that aggressive and extended treatment should be considered in clinical practice for smokers with schizophrenia. Furthermore, HV to address SHS exposure showed initial promise for assisting smokers with schizophrenia in maintaining abstinence, indicating that this intervention may be worthy of future research.

BackgroundThe FDA recently acquired regulatory authority over tobacco products, leading to renewed interest in whether reducing the nicotine content of cigarettes would reduce tobacco dependence in the United States. Given the association between depressive symptoms and cigarette smoking, it is important to consider whether smokers with elevated depressive symptoms experience unique benefits or negative consequences of nicotine reduction.MethodsIn this secondary analysis of a randomized clinical trial that examined the effects of cigarettes varying in nicotine content over a 6-week period in non-treatment-seeking smokers, we used linear regression to examine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine content (RNC) cigarettes, relative to normal-nicotine content (NNC) cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures.ResultsOf the 717 participants included in this analysis, 109 (15.2%) had CES-D scores ≥ 16, indicative of possible clinical depression. Relative to NNC cigarettes, RNC cigarettes reduced smoking rates, nicotine dependence, and cigarette craving, and these effects were not significantly moderated by baseline CES-D score. A significant interaction between baseline CES-D score and cigarette condition on week 6 CES-D score was observed (p < .05); among those with CES-D scores ≥ 16 at baseline, those assigned to RNC cigarettes had lower week 6 CES-D scores than those assigned to NNC cigarettes. Among those in the lowest nicotine content conditions, biochemically confirmed compliance with the RNC cigarettes was associated with an increase in CES-D score for those with baseline CES-D scores < 16 and no change in CES-D score for those with baseline CES-D scores ≥ 16.ConclusionsThese findings provide initial evidence that a reduced-nicotine standard for cigarettes may reduce smoking, without worsening depressive symptoms, among smokers with elevated depressive symptoms.ImplicationsThis secondary analysis of a recent clinical trial examined whether depressive symptom severity moderated the effects of reduced-nicotine cigarettes on smoking and depressive symptoms. Results indicate that, regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and craving at week 6 post-randomization than those assigned to normal-nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to normal-nicotine cigarettes. These results suggest that a nicotine reduction policy could have beneficial effects for smokers, regardless of depressive symptom severity.

IntroductionNonsmoking pregnant women in China have significant exposure to secondhand smoke (SHS). Few interventions have focused on pregnant women reducing their SHS exposure.MethodsThis clustered randomized controlled trial, conducted at eight hospitals in Sichuan, China, compared a prenatal health education intervention with usual clinical care as a control. The primary outcome was self-reported "no SHS exposure" before and 3 months after birth. The intervention consisted of three large group educational sessions, standardized clinician advice, brief monthly follow-up calls, and educational materials and resources. A random sample of participants was biochemically validated before birth with hair nicotine, a long-term biomarker of smoke exposure.ResultsOverall, 1181 participants were randomized to intervention (n = 526) and control (n = 655) groups. More participants in the intervention group than the control group reported no SHS exposure 3 months after birth (Total: 77.9% vs. 52.6%, P < .001; Home: 81.2% vs. 53.3%, P < .001). The intervention group also had greater changes in improved smoke-free homes and SHS knowledge and attitudes. Controlling for covariates, the intervention group was less likely to report SHS exposure than the control group (Total: OR = 0.47, 95% CI = 0.31 to 0.71; Home: OR = 0.33, 95% CI = 0.21 to 0.53), and this effect was sustained 3 months after birth. The adjusted log concentration of hair nicotine for the intervention group decreased by 0.28 log µg/g more than the control group.ConclusionsOur smoke-free health education intervention for nonsmoking pregnant women significantly reduced SHS exposure before and after birth. This intervention model can become part of a standard protocol for the care of pregnant women in hospital settings.

IntroductionThe nicotine metabolite ratio (NMR) of 3'-hydroxycotinine to cotinine is a noninvasive marker of the rate of nicotine metabolism. Fast metabolism (ie, a high NMR) is associated with lower cigarette smoking abstinence rates using transdermal nicotine replacement. We evaluated whether the NMR can be used to predict self-reported nicotine lozenge use and tobacco abstinence among smokeless tobacco users treated for tobacco dependence.MethodsThis was a secondary analysis of data from one arm of a large trial. Participants received quitting support materials and 4-mg nicotine lozenges by mail plus three coaching phone calls. Saliva kits were mailed for collection of saliva samples, which were analyzed for cotinine and 3'-hydroxycotinine. Self-reported tobacco and lozenge use were assessed at 3 months. Analyses were performed using Spearman rank correlation and logistic regression.ResultsOf the 160 saliva collection kits mailed, 152 were returned. The NMR was not significantly correlated with the baseline amount of smokeless tobacco used, the number of years of tobacco use, or the level of tobacco dependence as measured by the Severson Smokeless Tobacco Dependency Scale. The NMR was positively correlated with lozenge use (r = 0.21, P = .015), but it did not predict self-reported 7-day point prevalence abstinence at 3 months.ConclusionsFast metabolizers may need to self-administer more nicotine replacement in the form of nicotine lozenges to achieve the same clinical response achieved by slower metabolizers using fewer lozenges.

IntroductionThe Food and Drug Administration has the authority to regulate tobacco product constituents, including nicotine, to promote public health. Reducing the nicotine content in cigarettes may lead to lower levels of addiction. Smokers however may compensate by smoking more cigarettes and/or smoking more intensely. The objective of this study was to test whether individual differences in the level of nicotine dependence (as measured by the Fagerstrom Test of Cigarette Dependence [FTCD]) and/or the rate of nicotine metabolism influence smoking behavior and exposure to tobacco toxicants when smokers are switched to reduced nicotine content cigarettes (RNC).MethodsData from 51 participants from a previously published clinical trial of RNC were analyzed. Nicotine content of cigarettes was progressively reduced over 6 months and measures of smoking behavior, as well as nicotine metabolites and tobacco smoke toxicant exposure, CYP2A6 and nicotinic CHRNA5-A3-B4 (rs1051730) genotype were measured.ResultsHigher baseline FTCD predicted smoking more cigarettes per day (CPD), higher cotinine and smoke toxicant levels while smoking RNC throughout the study, with no interaction by RNC level. Time to first cigarette (TFC) was associated with differences in compensation. TFC within 10 min was associated with a greater increase in CPD compared to TFC greater than 10 min. Neither rate of nicotine metabolism, nor CYP2A6 or nicotinic receptor genotype, had an effect on the outcome variables of interest.ConclusionsFTCD is associated with overall exposure to nicotine and other constituents of tobacco smoke, while a short TFC is associated with an increased compensatory response after switching to RNC.

IntroductionRates of obesity are higher among more dependent smokers and 37%-65% of smokers seeking cessation treatment are overweight or obese. Overweight or obese smokers may possess metabolic and neurobiological features that contribute to difficulty achieving cessation using front-line nicotine replacement products. Attention to factors that facilitate effective cessation treatment in this vulnerable population is needed to significantly reduce mortality risk among overweight and obese smokers.MethodThis secondary analysis of 2 large trials of transdermal nicotine replacement in general medical practices evaluated the hypothesis that higher body mass index (BMI) would moderate the efficacy of the nicotine patch. We examined the potential for gender to further moderate the relationship between BMI and treatment efficacy.ResultsIn the placebo controlled trial (N = 1,621), 21-mg patch was no more effective than placebo for assisting biochemically verified point prevalence abstinence up to 1 year after quitting for women with higher BMI, but appeared to be effective for men at normal or high BMI (gender × BMI beta = -0.22, p = .004). We did not find differential long-term cessation outcomes among male or female smokers in the 15-mg patch trial (n = 705). However, we observed significantly higher rates of early lapse among women with higher BMI treated with nicotine patch across both trials.ConclusionThese results suggest that increased BMI may affect the efficacy of nicotine patch on reducing risk of early lapse in women. Additional research is needed to explore mechanisms of risk for decreased efficacy of this commonly used cessation aid.

IntroductionTreatment of tobacco use in mental health settings is rare despite high rates of comorbidity. With a focus on early intervention, we evaluated a tobacco treatment intervention among adolescents and young adults recruited from outpatient, school-based, and residential mental health settings and tested for gender differences.MethodsIntervention participants received computerized motivational feedback at baseline, 3 months, and 6 months and were offered 12 weeks of cessation counseling and nicotine patches. Usual care participants received a self-help guide and brief cessation advice. We examined 7-day point prevalence abstinence with biochemical confirmation at 3, 6, and 12 months; smoking reduction; and 24-hr quit attempts.ResultsAt baseline, the sample (N = 60, 52% female, mean age = 19.5±2.9 years, 40% non-Hispanic Caucasian) averaged 7±6 cigarettes/day, 62% smoked daily, 38% smoked ≤ 30 min of waking, 12% intended to quit in the next month, 47% had a parent who smoked, and 3 of 5 of participants' closest friends smoked on average. During the 12-month study, 47% of the sample reduced their smoking, 80% quit for 24 hr, and 11%, 13%, and 17% confirmed 7-day point prevalence abstinence at 3-, 6-, and 12-month follow-up, respectively, with no differences by treatment condition (ps > .400). Over time, abstinence was greater among girls (adjusted odds ratio [AOR] = 8.9) than among boys, and abstinence was greater for lighter smokers than heavier smokers (AOR = 4.5) (p < .05). No mental health or other measured variables predicted abstinence.ConclusionsAdolescent and young adult smokers with mental health concerns are a challenging group to engage and to effectively treat for tobacco addiction, particularly heavier smokers and boys. Innovative approaches are needed.

IntroductionThe purpose of this study was to characterize the performance of disposable button-activated and disposable airflow-activated electronic cigarettes (EC) and electronic hookahs (EH).MethodsThe airflow rate required to produce aerosol, pressure drop, and the aerosol absorbance at 420 nm were measured during smoke-outs of 9 disposable products. Three units of each product were tested in these experiments.ResultsThe airflow rates required to produce aerosol and the aerosol absorbances were lower for button-activated models (3 mL/s; 0.41-0.55 absorbance) than for airflow-activated models (7-17 mL/s; 0.48-0.84 absorbance). Pressure drop was also lower across button-activated products (range = 6-12 mm H2O) than airflow-activated products (range = 15-67 mm H20). For 25 of 27 units tested, airflow did not have to be increased during smoke-out to maintain aerosol production, unlike earlier generation models. Two brands had uniform performance characteristics for all parameters, while 3 had at least 1 product that did not function normally. While button-activated models lasted 200 puffs or less and EH airflow-activated models often lasted 400 puffs, none of the models produced as many puffs as advertised. Puff number was limited by battery life, which was shorter in button-activated models.ConclusionThe performance of disposable products was differentiated mainly by the way the aerosol was produced (button vs airflow-activated) rather than by product type (EC vs EH). Users needed to take harder drags on airflow-activated models. Performance varied within models, and battery life limited the number of puffs. Data suggest quality control in manufacturing varies among brands.

IntroductionSexual and gender minority individuals (i.e., lesbian, gay, bisexual, and transgender [LGBT]) have a higher smoking prevalence than nonminority individuals. There is limited evidence of smoking abstinence success in nontailored smoking treatments among LGBT smokers.MethodsThis study is a secondary data analysis comparing the efficacy of extended, nontailored treatments among sexual and gender minority and nonminority smokers. Data from two clinical trials were combined to increase power and generalizability of the findings. Trials began with 12 weeks of counseling, nicotine replacement, and bupropion, after which participants were randomized to an extended treatment.ResultsFollow-up occurred at weeks 12, 24, 52, 64, and 104. Of the sample (n = 777), 17% identified as sexual and gender minority and 83% as nonminority. The sample was 75% non-Hispanic White, with 86% completing at least some college, and 68% were employed. Sexual and gender minorities were younger and indicated a greater desire to quit smoking than nonminority smokers. No other differences emerged on demographic, smoking, or mood variables. The average Fagerström Test for Nicotine Dependence score was 4.8, and mean daily cigarettes was 19.8. The generalized estimating equations model revealed no significant differences in abstinence between sexual and gender minority smokers and nonminority smokers at all follow-up assessments.ConclusionsSexual and gender minority smokers appear as likely to quit or abstain as nonminority smokers in extended, nontailored interventions. However, these findings may not generalize to other geographic areas, where access to treatment is limited or a higher stigma of sexual orientation exists.

IntroductionWe examined homes of hookah-only smokers and nonsmokers for levels of indoor air nicotine (a marker of secondhand smoke) and indoor surface nicotine (a marker of thirdhand smoke), child uptake of nicotine, the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the toxicant acrolein by analyzing their corresponding metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL) and 3-hydroxypropylmercapturic acid.MethodsData were collected at 3 home visits during a 7-day study period from a convenience sample of 24 households with a child 5 years or younger. Three child urine samples and 2 air and surface samples from the living room and the child bedroom were taken in homes of nonsmokers (n = 5) and hookah-only smokers (n = 19) comprised of daily hookah smokers (n = 8) and weekly/monthly hookah smokers (n = 11).ResultsNicotine levels in indoor air and on surfaces in the child bedrooms in homes of daily hookah smokers were significantly higher than in homes of nonsmokers. Uptake of nicotine, NNK, and acrolein in children living in daily hookah smoker homes was significantly higher than in children living in nonsmoker homes. Uptake of nicotine and NNK in children living in weekly/monthly hookah smoker homes was significantly higher than in children living in nonsmoker homes.ConclusionsOur data provide the first evidence for uptake of nicotine, the tobacco-specific lung carcinogen NNK, and the ciliatoxic and cardiotoxic agent acrolein in children living in homes of hookah smokers. Our findings suggest that daily and occasional hookah use in homes present a serious, emerging threat to children's long-term health.