Indicators of Tobacco Dependence Among Youth: Findings From Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health Study.

BACKGROUND: Prior work established a measure of tobacco dependence (TD) among adults that can be used to compare TD across different tobacco products. We extend this approach to develop a common, cross-product metric for TD among youth. METHODS: One thousand one hundred and forty-eight youth aged 12-17 who used a tobacco product in the past 30 days were identified from 13 651 youth respondents in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study. FINDINGS: Analyses confirmed a single primary latent construct underlying responses to TD indicators for all mutually exclusive tobacco product user groups. Differential Item Functioning analyses supported the use of 8 of 10 TD indicators for comparisons across groups. With TD levels anchored at 0.0 (standard deviation [SD] = 1.0) among cigarette only (n = 265) use group, mean TD scores were more than a full SD lower for e-cigarette only (n = 150) use group (mean = -1.09; SD = 0.64). Other single product use group (cigar, hookah, pipe, or smokeless; n = 262) on average had lower TD (mean = -0.60; SD = 0.84), and the group with the use of multiple tobacco products (n = 471) experienced similar levels of TD (mean = 0.14; SD = 0.78) as the cigarette only use group. Concurrent validity was established with product use frequency among all user groups. A subset of five TD items comprised a common metric permitting comparisons between youth and adults. CONCLUSION: The PATH Study Youth Wave 1 Interview provided psychometrically valid measures of TD that enable future regulatory investigations of TD across tobacco products and comparisons between youth and adult tobacco product use group. IMPLICATIONS: A measure of tobacco dependence (TD) has been established previously among adults to compare TD across tobacco products. This study established the validity of a similar, cross-product measure of TD among youth. Findings suggest a single latent TD construct underlying this measure, concurrent validity of the scale with product use frequency across different types of tobacco users, and a subset of common items that can be used to compare TD between youth and adults who use tobacco.

Role of e-cigarettes and pharmacotherapy during attempts to quit cigarette smoking: The PATH Study 2013-16.

BACKGROUND: More smokers report using e-cigarettes to help them quit than FDA-approved pharmacotherapy. OBJECTIVE: To assess the association of e-cigarettes with future abstinence from cigarette and tobacco use. DESIGN: Cohort study of US sample, with annual follow-up. PARTICIPANTS: US adult (ages 18+) daily cigarette smokers identified at Wave 1 (W1; 2013-14) of the PATH Study, who reported a quit attempt before W2 and completed W3 (n = 2443). EXPOSURES: Use of e-cigarettes, pharmacotherapy (including nicotine replacement therapy), or no product for last quit attempt (LQA), and current daily e-cigarette use at W2. ANALYSIS: Propensity score matching (PSM) of groups using different methods to quit. OUTCOME MEASURES: 12+ months abstinence at W3 from cigarettes and from all tobacco (including e-cigarettes). 30+ days abstinence at W3 was a secondary outcome. RESULTS: Among daily smokers with an LQA, 23.5% used e-cigarettes, 19.3% used pharmacotherapy only (including NRT) and 57.2% used no product. Cigarette abstinence for 12+ months at W3 was ~10% in each group. Half of the cigarette abstainers in the e-cigarette group were using e-cigarettes at W3. Different methods to help quitting had statistically comparable 12+ month cigarette abstinence at W3 (e-cigarettes vs no product: Risk Difference (RD) = 0.01, 95% CI: -0.04 to 0.06; e-cigarettes vs pharmacotherapy: RD = 0.02, 95% CI:-0.04 to 0.09). Likewise, daily e-cigarette users at W2 did not show a cessation benefit over comparable no-e-cigarette users and this finding was robust to sensitivity analyses. Abstinence for 30+ days at W3 was also similar across products. LIMITATIONS: The frequency of e-cigarette use during the LQA was not assessed, nor was it possible to assess continuous abstinence from the LQA. CONCLUSION: Among US daily smokers who quit cigarettes in 2014-15, use of e-cigarettes in that attempt compared to approved cessation aids or no products showed similar abstinence rates 1-2 years later.

Abuse liability of electronic cigarettes in men who are experienced electronic cigarette users.

Most electronic cigarettes (e-cigs) aerosolize a nicotine-containing liquid that users inhale. Few experimental studies have examined e-cig abuse liability (the extent to which use of these products may lead to persistent and/or problematic use). In this study, 24 experienced male e-cig users completed 4 sessions that differed byproduct used: own e-cig (OWN), an eGo e-cig filled with participants' own brand/flavor liquid in 0 mg/mL nicotine (e-cig0), an eGo e-cig filled with the highest nicotine concentration available in participants' own brand/flavor (e-cighighest), and a U.S. Food and Drug Administration-approved nicotine inhaler (IN). Outcome measures included crossover point on the multiple-choice procedure, plasma nicotine delivery, and subjective effect profile. After 10 puffs, a significantly higher mean crossover point was observed for OWN at $1.35 (SD = 0.90) compared to e-cighighest at $0.88 (SD = 0.89), e-cig0 at $0.83 (SD = 0.79), and IN at $0.72 (SD = 0.84). Significant increases in mean plasma nicotine concentration were observed for OWN at 7.94 ng/mL (SD = 6.19) and e-cighighest at 7.51 ng/mL (SD = 5.39). Significant reductions in abstinence symptom suppression and higher ratings of satisfaction were observed for OWN and e-cighighest, with significantly less suppression and lower ratings of satisfaction for e-cig0 and IN. These findings suggest that human laboratory methods can be used to assess e-cig abuse liability and that nicotine-containing e-cigs have greater abuse liability than nicotine-free e-cigs and the IN. Potential regulations intended to limit e-cig abuse liability should be tested using these or similar procedures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Abuse liability assessment of an electronic cigarette in combustible cigarette smokers.

Under certain conditions, electronic cigarettes (e-cigs) can deliver nicotine to and suppress tobacco abstinence symptoms in cigarette smokers. Growing popularity of e-cigs raises abuse liability concerns. This study's purpose was to compare the abuse liability of an e-cig (1.5 Ohm, 3.3 V) filled with 36 mg/mL or 0 mg/mL nicotine to an Food and Drug Administration (FDA)-approved nicotine inhaler (IN) and participants' own brand (OB) of cigarettes. Smokers (N = 24) completed four sessions in which they completed the multiple-choice procedure, and plasma nicotine concentration and subjective effects were measured. Mean (SD) multiple-choice procedure crossover point was $0.87 (1.0) for the 36-mg/mL nicotine e-cig and $0.96 (1.2) for the 0-mg/mL e-cig, significantly higher than the IN mean of $0.32 (0.6) but significantly lower than the OB cigarette mean of $1.42 (1.4). Ten puffs from an own-brand cigarette increased mean plasma nicotine concentration from 3.55 (2.8) to 13.64 (9.8) ng/mL, as compared to an increase from 3.16 (1.8) to 8.51 (5.4) ng/mL for the 36-mg/mL e-cig. The 36-mg/mL e-cig reduced nicotine abstinence symptoms more than the 0-mg/mL e-cig, and both e-cigs were rated as more reinforcing than the inhaler but less reinforcing than participants' OB cigarettes (ps < .05). Results suggest that the e-cig examined had higher abuse liability than the IN but lower than combustible cigarettes. These data and methods may be useful for policymakers by revealing how e-cig abuse liability compares to tobacco/nicotine products with abuse liability profiles that are well established. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Differences in puff topography, toxicant exposure, and subjective response between waterpipe tobacco smoking men and women.

Waterpipe tobacco smoking (WTS) exposes users to toxicants in much greater amounts than a cigarette. Little is known about how gender affects WTS toxicant exposure and subjective response. Data from three WTS clinical laboratory studies were combined for analysis. Participants (N = 99; 38 women) completed a 45-min WTS session where they smoked a waterpipe ad libitum. Puff topography was measured throughout, and plasma nicotine concentration, expired air carbon monoxide (CO), and subjective responses were measured pre- and post-WTS. There was a gender effect for total puff volume with men inhaling a greater smoke volume, on average (M = 59.9 L, SD = 40.7), compared with women (M = 38.8 L, SD = 27.8; p < .01). Men had greater post-WTS mean plasma nicotine concentrations (M = 10.0 ng/ml, SD = 7.1) compared with women (M = 6.9 ng/ml, SD = 5.2; p < .05). Post-WTS expired air CO was not associated with gender (men M = 27.6 ppm, SD = 18.9; women M = 22.7 ppm, SD = 17.0, ns). Relative to men, women had higher post-WTS scores for subjective measures of "nauseous," "dizzy," "nervous," "headache," and "heart pounding." Men and women are exposed to toxicants during WTS, and men may achieve higher nicotine exposure than women, likely resulting from differences in smoke inhaled. However, similar post-WTS expired air CO between men and women and higher ratings of negative subjective responses among women may indicate that factors beyond puff topography may impact toxicant exposure and subjective response to WTS. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Electronic cigarette user plasma nicotine concentration, puff topography, heart rate, and subjective effects: Influence of liquid nicotine concentration and user experience.

Electronic cigarette (ECIG) nicotine delivery and other effects may depend on liquid nicotine concentration and user experience. This study is the first to systematically examine the influence of ECIG liquid nicotine concentration and user experience on nicotine delivery, heart rate, puff topography, and subjective effects. Thirty-three ECIG-experienced individuals and 31 ECIG-naïve cigarette smokers completed 4 laboratory conditions consisting of 2, 10-puff bouts (30-sec interpuff interval) with a 3.3-V ECIG battery attached to a 1.5-Ω "cartomizer" (7.3 W) filled with 1 ml ECIG liquid. Conditions differed by liquid nicotine concentration: 0, 8, 18, or 36 mg/ml. Participants' plasma nicotine concentration was directly related to liquid nicotine concentration and dependent on user experience, with significantly higher mean plasma nicotine increases observed in ECIG-experienced individuals relative to ECIG-naïve smokers in each active nicotine condition. When using 36 mg/ml, mean plasma nicotine increase for ECIG-experienced individuals was 17.9 ng/ml (SD = 17.2) and 6.9 (SD = 7.1; p < .05) for ECIG-naïve individuals. Between-group differences were likely due to longer puffs taken by experienced ECIG users: collapsed across condition, mean puff duration was 5.6 sec (SD = 3.0) for ECIG-experienced and 2.9 (SD = 1.5) for ECIG-naïve individuals. ECIG use also suppressed nicotine/tobacco abstinence symptoms in both groups; the magnitude of abstinence symptom suppression depended on liquid nicotine concentration and user experience. These and other recent results suggest that policies intended to limit ECIG nicotine delivery will need to account for factors in addition to liquid nicotine concentration (e.g., device power and user behavior). (PsycINFO Database Record

Electronic cigarettes: what are they and what do they do?

Electronic cigarettes (ECIGs) use electricity to power a heating element that aerosolizes a liquid containing solvents, flavorants, and the dependence-producing drug nicotine for user inhalation. ECIGs have evolved rapidly in the past 8 years, and the changes in product design and liquid constituents affect the resulting toxicant yield in the aerosol and delivery to the user. This rapid evolution has been accompanied by dramatic increases in ECIG use prevalence in many countries among adults and, especially, adolescents in the United States. The increased prevalence of ECIGs that deliver nicotine and other toxicants to users' lungs drives a rapidly growing research effort. This review highlights the most recent information regarding the design of ECIGs and their liquid and aerosol constituents, the epidemiology of ECIG use among adolescents and adults (including correlates of ECIG use), and preclinical and clinical research regarding ECIG effects. The current literature suggests a strong rationale for an empirical regulatory approach toward ECIGs that balances any potential ECIG-mediated decreases in health risks for smokers who use them as substitutes for tobacco cigarettes against any increased risks for nonsmokers who may be attracted to them.

Clinical Laboratory Evaluation of Electronic Cigarettes/Electronic Nicotine Delivery Systems: Methodological Challenges.

OBJECTIVE: Evaluating electronic cigarettes (ECIGs) in the clinical laboratory is critical to understanding their effects. However, laboratory evaluation of ECIGs can be challenging, as they are a novel, varied, and evolving class of products. The objective of this paper is to describe some methodological challenges to the clinical laboratory evaluation of ECIGs. METHODS: The authors gathered information about challenges involved in the laboratory evaluation of ECIGs. Challenges were categorized and solutions provided when possible. RESULTS: Methods used to study combustible cigarettes may need to be adapted to account for ECIG novelty and differences within the class. Challenges to ECIG evaluation can include issues related to 1) identification of ECIG devices and liquids, 2) determination of short -term ECIG abstinence, 3) measurement of use behavior, and 4) assessment of dependence. These challenges are discussed, and some suggestions to inform ECIG evaluation using clinical laboratory methods are provided. CONCLUSIONS: Awareness of challenges and developing, validating, and reporting methods used to address them aids interpretation of results and replication efforts, thus enhancing the rigor of science used to protect public health through appropriate, empirically-based, ECIG regulation.

Group Waterpipe Tobacco Smoking Increases Smoke Toxicant Concentration.

INTRODUCTION: Waterpipe tobacco smoking is a global health concern. Laboratory research has focused on individual waterpipe users while group use is common. This study examined user toxicant exposure and smoke toxicant yield associated with individual and group waterpipe smoking. METHODS: Twenty-two pairs of waterpipe smokers used a waterpipe individually and as a dyad. Before and after smoking, blood was sampled and expired carbon monoxide (CO) measured; puff topography was recorded throughout. One participant from each pair was selected randomly and their plasma nicotine and expired air CO concentrations were compared when smoking alone to when smoking as part of a dyad. Recorded puff topography was used to machine-produce smoke that was analyzed for toxicant content. RESULTS: There was no difference in mean plasma nicotine concentration when an individual smoked as part of a dyad (mean = 14.9 ng/ml; standard error of the mean [SEM] = 3.0) compared to when smoking alone (mean = 10.0 ng/ml; SEM = 1.5). An individual smoking as part of as a dyad had, on average, lower CO (mean = 15.8 ppm; SEM = 2.0) compared to when smoking alone (mean= 21.3 ppm; SEM = 2.7). When two participants smoked as a dyad they took, on average, more puffs (mean = 109.8; SEM = 7.6) than a singleton smoker (mean = 77.7; SEM = 8.1) and a shorter interpuff interval (IPI; dyad mean = 23.8 seconds; SEM = 1.9; singleton mean = 40.8 seconds; SEM = 4.8). Higher concentrations of several toxicants were observed in dyad-produced smoke. DISCUSSION: Dyad smoking may increase smoke toxicant content, likely due to the dyad's shorter IPIs and greater puff number. More work is needed to understand if group waterpipe smoking alters the health risks of waterpipe tobacco smoking. IMPLICATIONS: This study is the first to measure toxicants in smoke generated from a waterpipe when used by a dyad. Relative to smoke generated by a singleton, dyad smoke had higher concentration of some toxicants. These differences may be attributed to differences in puffing behavior, specifically the shorter IPI and greater puff number observed in the dyad condition. Relative to singleton smokers, dyad smokers were exposed to less CO, but nicotine exposure did not differ. More work is needed to assess the health effects of inhalation of more toxicant-laden smoke during group waterpipe use.

Effects of Electronic Cigarette Liquid Nicotine Concentration on Plasma Nicotine and Puff Topography in Tobacco Cigarette Smokers: A Preliminary Report.

INTRODUCTION: Electronic cigarettes (ECIGs) aerosolize a liquid that usually contains propylene glycol and/or vegetable glycerin, flavorants, and the dependence-producing drug nicotine in various concentrations. This study examined the extent to which ECIG liquid nicotine concentration is related to user plasma nicotine concentration in ECIG-naïve tobacco cigarette smokers. METHODS: Sixteen ECIG-naïve cigarette smokers completed four laboratory sessions that differed by the nicotine concentration of the liquid (0, 8, 18, or 36 mg/ml) that was placed into a 1.5 Ohm, dual coil "cartomizer" powered by a 3.3V battery. In each session, participants completed two, 10-puff ECIG use bouts with a 30-second inter-puff interval; bouts were separated by 60 minutes. Venous blood was sampled before and after bouts for later analysis of plasma nicotine concentration; puff duration, volume, and average flow rate were measured during each bout. RESULTS: In bout 1, relative to the 0mg/ml nicotine condition (mean = 3.8 ng/ml, SD = 3.3), plasma nicotine concentration increased significantly immediately after the bout for the 8 (mean = 8.8 ng/ml, SD = 6.3), 18 (mean = 13.2 ng/ml, SD = 13.2), and 36 mg/ml (mean = 17.0 ng/ml, SD = 17.9) liquid concentration. A similar pattern was observed after bout 2. Average puff duration in the 36 mg/ml condition was significantly shorter compared to the 0mg/ml nicotine condition. Puff volume increased during the second bout for 8 and 18 mg/ml conditions. CONCLUSIONS: For a given ECIG device, nicotine delivery may be directly related to liquid concentration. ECIG-naïve cigarette smokers can, from their first use bout, attain cigarette-like nicotine delivery profiles with some currently available ECIG products. IMPLICATIONS: Liquid nicotine concentration can influence plasma nicotine concentration in ECIG-naïve cigarette smokers, and, at some concentrations, the nicotine delivery profile of a 3.3V ECIG with a dual coil, 1.5-Ohm cartomizer approaches that of a combustible tobacco cigarette in this population. Finding a product that delivers nicotine as effectively as a tobacco cigarette, as we report here, may be essential for smokers who want to replace completely their combustible tobacco cigarettes with ECIGs.

Electronic cigarette nicotine delivery can exceed that of combustible cigarettes: a preliminary report.

INTRODUCTION: Electronic cigarettes (ECIGs) aerosolise a liquid that usually contains propylene glycol and/or vegetable glycerine, flavourants and the dependence-producing drug, nicotine, in various concentrations. This laboratory study examined the relationship between liquid nicotine concentration and plasma nicotine concentration and puffing behaviour in experienced ECIG users. METHODS: Sixteen ECIG-experienced participants used a 3.3-Volt ECIG battery attached to a 1.5-Ohm dual-coil 'cartomiser' loaded with 1 mL of a flavoured propylene glycol/vegetable glycerine liquid to complete four sessions, at least 2 days apart, that differed by nicotine concentration (0, 8, 18 or 36 mg/mL). In each session, participants completed two 10-puff ECIG-use bouts (30 s puff interval) separated by 60 min. Venous blood was sampled to determine plasma nicotine concentration. Puff duration, volume and average flow rate were measured. RESULTS: Immediately after bout 1, mean plasma nicotine concentration was 5.5 ng/mL (SD=7.7) for 0 mg/mL liquid, with significantly (p<0.05) higher mean concentrations observed for the 8 (mean=17.8 ng/mL, SD=14.6), 18 (mean=25.9 ng/mL, SD=17.5) and 36 mg/mL (mean=30.2 ng/mL; SD=20.0) concentrations; a similar pattern was observed for bout 2. For bout 1, at 36 mg/mL, the mean post- minus pre-bout difference was 24.1 ng/mL (SD=18.3). Puff topography data were consistent with previous results and revealed few reliable differences across conditions. DISCUSSION: This study demonstrates a relationship between ECIG liquid nicotine concentration and user plasma nicotine concentration in experienced ECIG users. Nicotine delivery from some ECIGs may exceed that of a combustible cigarette. The rationale for this higher level of nicotine delivery is uncertain.

A shift in the role of glutamatergic signaling in the nucleus accumbens core with the development of an addicted phenotype.

BACKGROUND: While dopamine signaling in the nucleus accumbens (NAc) plays a well-established role in motivating cocaine use in early nonaddicted stages, recent evidence suggests that other signaling pathways may be critical once addiction has developed. Given the importance of glutamatergic signaling in the NAc for drug seeking and relapse, here we examined its role in motivating cocaine self-administration under conditions known to produce either a nonaddicted or an addicted phenotype. METHODS: Following acquisition, male and female Sprague Dawley rats were given either short access (three fixed-ratio 1 sessions, 20 infusions/day) or extended 24-hour access (10 days; 4 trials/hour; up to 96 infusions/day) to cocaine. Following a 14-day abstinence period, motivation for cocaine was assessed under a progressive-ratio schedule, and once stable, the effects of intra-NAc infusions of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor antagonist CNQX (0, .01, .03, .1 µg/side) were determined. As an additional measure for the development of an addicted phenotype, separate groups of rats were screened under an extinction/cue-induced reinstatement procedure following abstinence from short-access versus extended-access self-administration. RESULTS: Motivation for cocaine and levels of extinction and reinstatement responding were markedly higher following extended-access versus short-access self-administration, confirming the development of an addicted phenotype in the extended-access group. CNQX dose-dependently reduced motivation for cocaine in the extended-access group but was without effect in the short-access group. CONCLUSIONS: These results suggest that the role of glutamatergic signaling in the NAc, though not essential for motivating cocaine use in nonaddicted stages, becomes critical once addiction has developed.

Diminished role of dopamine D1-receptor signaling with the development of an addicted phenotype in rats.

BACKGROUND: Although considerable evidence implicates dopamine D1-receptor signaling in the nucleus accumbens in motivation for cocaine during early stages of addiction, less is known with regard to its role after the development of addiction. Here, we examined its role in the development of an addicted phenotype in intact male and female rats, and in female rats that were either resistant or vulnerable to developing this phenotype. METHODS: Intact males, females, and ovariectomized (OVX) females with and without estradiol (vulnerable, OVX+E; resistant, OVX+Veh) were given either short access (ShA) (three fixed-ratio 1 sessions, maximum of 20 infusions) or 24-hour extended access (ExA) to cocaine for 10 days (4 trials/hour). Motivation for cocaine was assessed after a 14-day abstinence period with a progressive-ratio schedule. Once responding stabilized, the effects of intra-accumbens infusion of the D1-receptor antagonist, SCH-23390 (0, .3, 1.0, 3.0 µg), were examined. RESULTS: Motivation for cocaine was markedly higher after abstinence from ExA versus ShA self-administration in intact males and females, indicating the development of an addicted phenotype in these groups. Motivation for cocaine was also higher than ShA control subjects in OVX+E but not OVX+Veh females after ExA self-administration, confirming the categorization of these groups as vulnerable versus resistant. After ExA self-administration, intact males and females and OVX+E but not OVX+Veh females were less sensitive to the effects of D1-receptor antagonism as compared with their ShA counterparts. CONCLUSIONS: These results suggest that the role of D1-receptor signaling, although critical in "nonaddicted" stages, becomes diminished once addiction has developed.

Estradiol as a mechanism for sex differences in the development of an addicted phenotype following extended access cocaine self-administration.

Women progress more rapidly after initial cocaine use to addiction as compared with men. Similarly, female rats appear to require less cocaine exposure before developing an addicted phenotype with evidence implicating estradiol as a potential mechanism. The goals of this study were to determine whether there are sex differences in the magnitude of the addicted phenotype under optimized conditions that induce its development in both males and females and to determine the role of estradiol in this effect. Following acquisition, intact male and intact and ovariectomized (OVX) female rats with and without estradiol replacement were given access to cocaine (1.5 mg/kg per infusion) under either extended access (ExA; discrete trial procedure, 4 trials/h, 24 h/day, 10 days) or short access (ShA) conditions (20 infusions maximum/day, 3 days). Motivation to obtain cocaine (0.5 mg/kg/infusion), as assessed under a progressive-ratio schedule, was then examined following a 2-week abstinence period. Results showed that following ExA self-administration, both males and females developed an addicted phenotype, with 9 of 11 males and 8 of 10 females showing a greater than 15% increase in levels of motivation to obtain cocaine as compared with ShA controls. In contrast, within the OVX groups, responding was enhanced from control levels after ExA self-administration in estradiol-replaced rats only. These results suggest that while females may have an enhanced vulnerability to developing an addicted phenotype, they may be similar to males once addiction has developed. These results also suggest that estradiol is critically involved in the development of an addicted phenotype in females.