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Flavors enhance nicotine e-cigarette appeal by altering sensory experience. Females may be more sensitive to tobacco-associated cues and uniquely affected by flavor. The current study is an exploratory analysis to examine differences by sex on reward, appeal, and sensory experience of popular e-cigarette flavors. Adults (N = 121) who use cigarettes (≥1 cigarette/day) were enrolled in a laboratory study in which they vaped four e-cigarette flavors (tobacco, cherry, menthol, vanilla; in separate lab sessions) in one of two freebase nicotine concentrations (6 mg/ml,18 mg/ml). Following exposures, participants rated e-cigarette reward using the Drug Effects Questionnaire (DEQ), flavor and overall e-cigarette appeal using Labeled Hedonic Scales (LHS), and intensity of flavor, irritation, coolness, fruitiness, and sweetness using Generalized Labeled Magnitude Scales (gLMS). Linear mixed models were conducted for outcomes to analyze effects of sex, flavor, and sex x flavor interaction. For DEQ ratings, there was a trend (p =.08) toward a sex x flavor interaction, in which menthol flavor produced more reward than other flavors for females, but not males. For LHS ratings, there was a significant sex x flavor interaction (p =.03) for overall e-cigarette experience with females but not males rating menthol higher than other flavors. All gLMS scales but irritation showed that females generally had greater differences between flavors compared to males (ps ≤ 0.03). Menthol in e-cigarettes may play an important role in mediating appeal and/or reward among females. This may be due in part to their ability to better detect sensory effects of e-cigarettes. • Menthol affects e-cigarette appeal and reward for females who use cigarettes. • Males did not demonstrate differences in appeal or reward by e-cigarette flavor. • Females (v. males) demonstrate bigger differences in ratings of e-cigarette flavors. [ABSTRACT FROM AUTHOR]

Smokers with mental health conditions (MHCs) lose approximately 15 years of life relative to non-smokers without MHCs, of which two-thirds are attributable to smoking. The Food and Drug Administration (FDA) recently announced a new regulatory strategy for tobacco that includes a reduction in the nicotine content of cigarettes sold in the US to a minimally-addictive level. This action could improve cessation rates in smokers with MHCs by reducing their dependence on nicotine. However, nicotine reduction also could have unintended negative consequences in smokers with MHCs. Thus, it is important to conduct randomized controlled trials to investigate the potential effects of nicotine reduction in smokers with MHCs. Several studies of the acute or extended effects of nicotine reduction in smokers with emotional disorders or serious mental illness have been recently completed or are underway. Studies to date indicate that when smokers with MHCs are switched, under randomized, double-blind conditions, to cigarettes with very low nicotine content, they reduce their cigarette intake, with minimal or no effects on withdrawal, psychiatric symptoms, or compensatory smoking. However, some deleterious effects of nicotine reduction on cognitive performance measures in smokers with schizophrenia have been observed, which are offset by providing concurrent nicotine replacement. We review these studies and provide suggestions for potentially increasing the effectiveness of a nicotine reduction strategy for reducing smoking in people with MHCs. The research described was conducted in the United States in 2010-2018. [ABSTRACT FROM AUTHOR]

This report describes a systematic literature review of voucher and related monetary-based contingency management (CM) interventions for substance use disorders (SUDs) over 5.2years (November 2009 through December 2014). Reports were identified using the search engine PubMed, expert consultations, and published bibliographies. For inclusion, reports had to (a) involve monetary-based CM; (b) appear in a peer-reviewed journal; (c) include an experimental comparison condition; (d) describe an original study; (e) assess efficacy using inferential statistics; (f) use a research design allowing treatment effects to be attributed to CM. Sixty-nine reports met inclusion criteria and were categorized into 7 research trends: (1) extending CM to special populations, (2) parametric studies, (3) extending CM to community clinics, (4) combining CM with pharmacotherapies, (5) incorporating technology into CM, (6) investigating longer-term outcomes, (7) using CM as a research tool. The vast majority (59/69, 86%) of studies reported significant (p<0.05) during-treatment effects. Twenty-eight (28/59, 47%) of those studies included at least one follow-up visit after CM was discontinued, with eight (8/28, 29%) reporting significant (p<0.05) effects. Average effect size (Cohen's d) during treatment was 0.62 (95% CI: 0.54, 0.70) and post-treatment it was 0.26 (95% CI: 0.11, 0.41). Overall, the literature on voucher-based CM over the past 5years documents sustained growth, high treatment efficacy, moderate to large effect sizes during treatment that weaken but remain evident following treatment termination, and breadth across a diverse set of SUDs, populations, and settings consistent with and extending results from prior reviews. [ABSTRACT FROM AUTHOR]

Cigarette preference increases as a function of greater nicotine content, but manipulating cost can shift preference. The aims of the present study are to model whether (1) the behavioral-economic metric unit price (cost/reinforcer magnitude) accounts for preference shifts and (2) whether preference shifts toward reduced nicotine content are associated with smoking reductions. In a multisite study between 2015 and 2016, 169 daily smokers from vulnerable populations completed two concurrent-choice conditions examining preference for smoking normal (15.8 mg/g) and reduced (0.4 mg/g) nicotine content cigarettes. In Condition 1, both products were available at 10 responses/choice. In Condition 2, availability of the 0.4 mg/g dose remained at 10 responses/choice while the 15.8 mg/g dose was available on a progressive-ratio (PR) schedule wherein response cost increased following each choice. Unit prices were calculated by dividing dose by response requirement. Results were analyzed using ANOVA and binomial tests (p < .05). Participants preferred the 15.8 over 0.4 mg/g dose in Condition 1, but shifted preference to the 0.4 mg/g dose in Condition 2 (p < .001) immediately before the point in the PR progression where unit price for 15.8 dose exceeded unit price for the 0.4 dose (p < .001). This shift was associated with a reduction in smoking (p < .001). The unit price of nicotine appears to underpin cigarette product preference and may provide a metric for predicting preference and potentially impacting it through tobacco regulations. These results also demonstrate that reduced compared to normal nicotine content cigarettes sustain lower smoking rates discernible even under acute laboratory conditions and in vulnerable populations. [ABSTRACT FROM AUTHOR]

This study examines whether tobacco dependence severity moderates the acute effects of reducing nicotine content in cigarettes on the addiction potential of smoking, craving/withdrawal, or smoking topography. Participants (N = 169) were daily smokers with mild, moderate, or high tobacco-dependence severity using the Heaviness of Smoking Index. Following brief abstinence, participants smoked research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg nicotine/g tobacco) in a within-subject design. Results were analyzed using repeated measures analysis of co-variance. No main effects of dependence severity or interactions with nicotine dose were noted in relative reinforcing effects in concurrent choice testing or subjective effects on the modified Cigarette Evaluation Questionnaire. Demand for smoking in the Cigarette Purchase Task was greater among more dependent smokers, but reducing nicotine content decreased demand independent of dependence severity. Dependence severity did not significantly alter response to reduced nicotine content cigarettes on the Minnesota Tobacco Withdrawal Scale nor Questionnaire of Smoking Urges-brief (QSU) Factor-2 scale; dependence severity and dose interacted significantly on the QSU-brief Factor-1 scale, with reductions dependent on dose among highly but not mildly or moderately dependent smokers. Dependence severity and dose interacted significantly on only one of six measures of smoking topography (i.e., maximum flow rate), which increased as dose increased among mildly and moderately but not highly dependent smokers. These results suggest that dependence severity has no moderating influence on the ability of reduced nicotine content cigarettes to lower the addiction potential of smoking, and minimal effects on relief from craving/withdrawal or smoking topography. [ABSTRACT FROM AUTHOR]

The present systematic review examines whether very low nicotine content (VLNC) cigarettes ameliorate withdrawal-induced impairments in behavioral/cognitive performance. PubMed, PsycInfo, and Web of Science were searched for performance effects of VLNC cigarettes. For inclusion, reports had to be in English, published in a peer-reviewed journal through June 2017, examine VLNC cigarettes (<0.2mg nicotine yield), include ≥2hour smoking abstinence or reduced nicotine exposure, and examine performance. 19 of 1243 articles reviewed met inclusion criteria. Poorer performance after smoking VLNC versus normal nicotine content (NNC) cigarettes was observed across 7 of 10 domains, including reaction time (8/11), short-term memory (3/10), sustained attention (4/6), inhibitory control (1/4), long-term memory (3/3 studies), and response variability (2/2). In two studies, combining VLNC smoking with nicotine replacement therapy (NRT) resulted in performance that was comparable to performance after NNC smoking. VLNC versus NNC differences were not discerned in motor control/functioning (0/2), visuospatial processing (0/2), learning (0/1), or verbal fluency (0/1). Eleven of nineteen (58%) studies were rated of Good or Excellent quality. Overall, VLNC cigarettes may not fully ameliorate withdrawal-induced disruptions in performance, although this varies by domain, with the strongest evidence for reaction time. Importantly, combining VLNC cigarettes with NRT appears to ameliorate withdrawal that is not reduced by VLNC cigarettes alone. As only 19 studies were identified, many domains are under-investigated. A more thorough evaluation of the extent to which VLNC cigarettes affect withdrawal-impaired performance may be warranted. [ABSTRACT FROM AUTHOR]

Cigarette smoking is overrepresented in populations with psychiatric conditions and socioeconomic disadvantage. Greater understanding of the role of reinforcement and nicotine dependence in smoking among vulnerable populations may facilitate development of better targeted interventions to reduce smoking. Prior research demonstrated that individual differences in the reinforcing value of smoking and nicotine-dependence severity predicted total nicotine-exposure in vulnerable populations. The present study uses multivariate regression to address two aims: (1) Quantify the degree to which the reinforcing value of smoking, assessed using the Cigarette Purchase Task (CPT), and dependence severity assessed using the Fagerström Test of Nicotine Dependence and Brief Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) each account for individual differences in cotinine-plus-3'-hydroxycotinine (COT+3HC) levels. (2) Explore whether there is overlap in the variance accounted for by the CTP, FTND, and B-WISDM. Participants were 628 adults with co-morbid psychiatric conditions or socioeconomic disadvantage who smoked daily. The CPT, FTND, and B-WISDM models accounted for 23.76%, 32.45%, and 29.61% of the variance in COT+3HC levels, respectively. Adding CPT to the FTND model failed to increase the variance accounted for and adding it to the B-WISDM model did so by only 1.2% demonstrating considerable overlap in the variance in nicotine exposure levels accounted for by these three instruments. These results provide new knowledge on the relationship between individual differences in the reinforcing value of smoking and nicotine-exposure levels and suggest differences in reinforcing value may underpin a considerable portion of the variance in nicotine exposure accounted for by dependence severity. [ABSTRACT FROM AUTHOR]

This study determined whether young adults perceptions of how tobacco free nicotine (TFN) compared to tobacco-derived nicotine (TDN) were associated with curiosity to try or use TFN e-cigarettes. U.S. young adults aged 18-25 years (n = 1176) completed an online survey in October 2021. Survey questions assessed TFN awareness, curiosity, use, and perceptions of how flavor, taste, ease of access, cost, and harm compared between TFN and TDN. Participants were categorized into 3 groups: not curious to try TFN (n = 511, 43.5%), curious to try TFN (n = 348, 29.6%), and ever used TFN (n = 317, 27%). Multinomial logistic regression measured associations between perceptions and TFN curiosity and use (vs. not curious to try), with total number tobacco products used and demographics as covariates. Compared to young adults who were not curious to try TFN e-cigarettes, those who were curious perceived TFN as less addictive than TDN (aOR = 2.27; 95% CI =1.34-3.86). Those who had used TFN e-cigarettes perceived TFN as having flavors that tasted better (aOR = 1.80; 95% CI = 1.63-1.99), "smoother" (aOR = 1.88; 95% CI =1.18-2.99), and less like tobacco (aOR 1.94; 95% CI 1.23-3.05). Adjusted models did not show differences in perceptions between those who had tried TFN and those who were curious to try TFN. Young adults who were curious to try or had used TFN had more positive perceptions of TFN. As it is currently unclear whether synthetic nicotine carries the same health risks as TDN, ongoing surveillance of TFN uptake among young adults is warranted. [ABSTRACT FROM AUTHOR]

E-cigarette flavors can create sensations of sweetness and coolness while masking the aversiveness of nicotine. Recently, non-tobacco nicotine (NTN) products were introduced to the market, but little is known about flavors in NTN e-cigarette use. We examined associations between flavors (i.e., sweet, mint/menthol) and susceptibility to and use of NTN e-cigarettes. 1239 US young adults (18–25 years) completed an anonymous, online survey in Fall 2021. The analytic sample included 520 participants who had used e-cigarettes and heard of NTN. Multinomial logistic regression models analyzed associations of flavored e-cigarette use (sweet and mint/menthol) with NTN e-cigarette use status (i.e., current [past-month] use, past [ever but not current] use, susceptible to use, and non-susceptible to use [reference]). Overall, 46.2% of participants reported current NTN use, 14.8% reported past use, 16.7% were susceptible to use, and 22.3% reported no susceptibility. Participants reported dual-use of sweet and mint/menthol NTN e-cigarette flavors (56.5%), sweet flavors use (24.8%), and mint/menthol flavor use (1.7%). Ever dual use of sweet and mint/menthol flavors was associated with current (OR = 9.64, 95%CI: 3.21–28.98) and past NTN e-cigarette use (8.30, [2.10–32.80]). Ever sweet flavor use was associated with current NTN use (3.80, 95%CI: 1.44–10.03) and susceptibility to future use (4.25, [1.53–11.81]). Similar findings were observed for mint/menthol flavors (current: 5.03, [1.41–17.99]; susceptible: 5.65, [1.64–19.51]). The use of sweet and mint/menthol flavors was significantly associated with NTN e-cigarette use among US young adults, highlighting the need for ongoing surveillance of flavored NTN e-cigarettes and appropriate regulations to discourage use. • Sweet flavor use was related to current use and susceptibility to NTN e-cigarettes. • Mint/menthol flavor use was related to current use and susceptibility to NTN e-cigarettes. • Dual sweet and mint/menthol flavor use was related to current and past NTN e-cigarette use. • Regulating sweet and mint/menthol flavors may help to reduce NTN product use. [ABSTRACT FROM AUTHOR]

We examined whether elucidating underpinning smoking motivation and related pharmacological processes enhances understanding of nicotine dependence among smokers from vulnerable populations. Data were obtained between Oct, 2016 and Sept, 2019 from 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage at University of Vermont, Brown University, Johns Hopkins University. Smoking motivation was assessed using the Cigarette Purchase Task (CPT), a behavioral-economic task that models the relative reinforcing value of smoking under varying monetary constraint. Dependence severity was measured using the Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence total scores (FTND), and FTND total scores minus items 1 and 4 (FTND2,3,5,6). We also assessed associations between dependence severity and smoking motivation with nicotine levels and metabolism rate. Principal Component Analysis was used to examine the latent structure of the conventional five CPT indices; bivariate and multivariable modeling was used to test associations. Factor analysis resulted in a two-factor solution, Amplitude (demand unconstrained by price) and Persistence (price sensitivity). CPT latent factors were associated with each dependence-severity measure (ps ≤ 0.0001), with associations stronger for Amplitude than Persistence across each, especially HSI which was exclusively associated with Amplitude. Amplitude and each dependence measure were associated with nicotine intake (ps ≤ 0.0002); Persistence was not (p = .19). Demand Amplitude more than Persistence appears key to understanding individual differences in dependence severity. Regarding potential application, the results suggest a need for interventions that more effectively target demand Amplitude to make greater headway in reducing smoking in vulnerable populations. Trial Registration:clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534. [ABSTRACT FROM AUTHOR]

This study examines the demographic factors associated with youths' first product tried (i.e., cigarettes, e-cigarettes, cigars, hookah, or smokeless tobacco). This study also evaluates whether the first product tried is associated with future nicotine product use (i.e., no use, single product use, and multiple product use) and nicotine dependence. Participants were 1999 youths (ages 12–17 years) who had ever tried a nicotine product and completed the Population Assessment of Tobacco Health study's Wave 1 (2013–2014) and Wave 4 (2016–2018) assessments. Two separate multinomial logistic regression models examined the association between 1) demographic factors and the first product tried at Wave 1 and 2) the first product tried at Wave 1 and past-30-day product use status at Wave 4. A two-part multivariable model examined the association between the first product tried and nicotine dependence, with part 1 modeling the presence (or absence) of any symptom of dependence and part 2 modeling the degree of dependence among those with any symptom of dependence. The first product tried was associated with sex, race, urbanicity, and parent education. First trying smokeless tobacco (vs. e-cigarettes) was associated with a greater likelihood of multiple product use (vs. no use and vs. single product use). Regarding the degree of nicotine dependence (n = 713), first trying smokeless tobacco (vs. e-cigarettes) was associated with higher nicotine dependence scores among those with any symptom of dependence. Youths who first try smokeless tobacco (vs. e-cigarettes) may be at higher risk for future multiple product use and more symptoms nicotine dependence. Research should explore tailored interventions for smokeless tobacco users. • We examined first nicotine product tried and multiple product use (MPU). • First trying smokeless tobacco (FT-ST; vs. e-cigarettes) was associated with MPU. • FT-ST (vs. e-cigarettes) was associated with higher nicotine dependence scores. [ABSTRACT FROM AUTHOR]

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that the hypothetical Cigarette Purchase Task (CPT), especially its demand Intensity index (i.e., estimated cigarettes participants would smoke if free), is associated with individual differences in smoking risk. Nevertheless, few studies have examined the extent to which hypothetical CPT demand Intensity may differ from consumption when participants are provided with free cigarettes. That topic is the overarching focus of the present study. Participants were 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage. CPT was administered for usual-brand cigarettes prior to providing participants with seven days of their usual-brand cigarettes free of cost and consumption was recorded daily via an Interactive Voice Response (IVR) System. Demand Intensity was correlated with IVR smoking rate (rs 0.670-0.696, ps < 0.001) but estimates consistently exceeded IVR smoking rates by an average of 4.4 cigarettes per day (ps < 0.001). Importantly, both measures were comparably sensitive to discerning well-established differences in smoking risk, including greater cigarettes per day among men versus women (F(1,732) = 18.74, p < 0.001), those with versus without opioid-dependence (F(1,732) = 168.37, p < 0.001), younger versus older adults (F(2,730) = 32.93, p < 0.001), and those with lower versus greater educational attainment (F(1,732) = 38.26, p < 0.001). Overall, CPT demand Intensity appears to overestimate consumption rates relative to those observed when participants are provided with free cigarettes, but those deviations are systematic (i.e., consistent in magnitude and direction, Fs all <1.63; ps > 0.19 for all interactions with subgroups). This suggests that demand Intensity was sensitive to established group differences in smoking rate, supporting its utility as an important measure of addiction potential. [ABSTRACT FROM AUTHOR]