Nicotine & Tobacco Research

Genome-wide association studies have identified associations between variation at rs16969968/rs1051730 in the CHRNA5-A3-B4 gene cluster and smoking related outcomes. Experiments in rodents have described the nicotinic acetylcholine receptors (nAChRs) subunits encoded by this gene cluster and showed a lack of nicotine aversion in nAChRs deficient animal models. We conducted a nicotine challenge and a smoking topography study in humans, hypothesising that: 1. responses to a nicotine challenge would differ according to the rs16969968/rs1051730 genotype and 2. genotype may influence nicotine intake via smoking topography.\n\nWe used linear regressions to examine associations between rs16969968/rs1051730 genotype and subjective (questionnaires) and objective (physiological parameters) responses following acute nicotine exposure in never smokers (hypothesis 1) or cigarette smoking in current smokers (hypothesis 2). There was evidence to suggest nicotine exposure increases blood pressure and heart rate, and negatively affects mood, but insufficient evidence that these effects differ by genotype. Carriers of the minor allele following smoking one cigarette, exhibited reduced cravings (b=-2.46, 95% CI -4.87 to - 0.06, p=0.04) and inhaled less smoke per cigarette (b=-0.24, 95% CI - 0.43 to - 0.06, p=0.01) and per puff (b=-0.18, 95% CI -0.32 to -0.01, p=0.02). These results suggest that we need to carefully consider the translational value of the findings of aversion behaviour in nAChRs rodent models, and that deeper inhalation does not explain the strong association between rs16969968/rs1051730 genotype and objective biomarkers of tobacco exposure.

IntroductionIncreased salience of drug-related cues over non-drug reinforcers can drive drug use and contribute to tobacco use disorder (TUD). An important scientific and clinical goal is to effectively measure this elevated drug-seeking behavior in TUD. However, most TUD assessments rely on self-reported cravings and cigarette consumption, not providing an objective measure of the impact of drug-cues on biasing behavior towards drugs. The probabilistic image choice (PIC) task investigates the choice of viewing drug-related pictures as compared to other salient pictures (e.g., pleasant and unpleasant). This study aimed to develop and validate the PIC task for TUD and evaluate the associations between behavioral choice and tobacco craving, daily cigarette consumption, quit attempts and motivation to quit, and nicotine dependence (the Fagerstrom score). MethodsWe recruited 468 smokers and 121 nonsmokers using the Prolific online platform. Participants performed the PIC task twice (at a one-month interval) and completed other measures relevant to TUD. Resultscompared to nonsmokers, tobacco smokers selected to view significantly more tobacco images and less pleasant (non-drug reinforcer) images, a profile that remained stable at retest. Individual differences in choice of tobacco as compared to pleasant images on the PIC task were associated with craving but not with the other tobacco dependence measures, suggesting that the task may serve as a behavioral proxy measure of drug "wanting" rather than of cumulative nicotine exposure or physical dependence. Conclusionsthese results suggest that the PIC task can be a valuable tool for objectively assessing craving-associated tobacco seeking in TUD. Implications section, which should provide a brief description about what the study adds. Most of the current measures of tobacco use disorder (TUD) rely on self-reports of consumption, dependence and craving and do not take into consideration the role of drug-related cues in driving tobacco seeking. This study shows that the probabilistic image choice (PIC) task provides an objective, reliable proxy measure of tobacco image seeking behavior in cigarette smokers that is linked to craving (desire) for smoking but not to other measures of TUD. Therefore, the PIC task may be a useful complementary tool for the classification, diagnosis, and prognosis of TUD.

IntroductionThe FDA announced its intention to issue proposed product standards banning menthol as a characterizing flavor in cigarettes and cigars. The public health benefits of these product standards may be attenuated by the role of plausible substitutes in the marketplace. Therefore, the present study examined the addiction potential of plausible combustible menthol alternatives compared to usual brand menthol cigarettes (UBMC). MethodsEighty adult menthol cigarette smokers completed four visits, smoking their UBMC at the first session and 3 menthol cigarette alternatives in random order at the subsequent visits: 1) a pre-assembled menthol roll-your-own cigarette using menthol pipe tobacco and mentholated cigarette tube (mRYO), 2) a menthol filtered little cigar (mFLC), and 3) a non-menthol cigarette (NMC). Measures of smoking topography, exhaled carbon monoxide (CO), craving and withdrawal, subjective effects, and behavioral economic demand indices were assessed. ResultsCompared to UBMC, menthol cigarette alternatives resulted in similar topography and CO exposure but significantly lower levels of positive subjective experience and behavioral economic demand indices. Among the alternative products, participants reported the highest level of positive subjective experience and higher demand for mRYO, compared with mFLC and NMC. Similarly, participants were significantly more likely to want to try again, purchase, and use the mRYO product regularly compared with mFLC and NMC. Conclusions and RelevancemRYO cigarettes were the most highly rated cigarette alternative among study products, suggesting their potential appeal as a menthol cigarette substitute and needed inclusion of menthol pipe tobacco and cigarette tubes in FDAs proposed ban. What is already known on this topicMenthol cigarettes are associated with increased smoking initiation, higher nicotine dependence, and decreased adult cessation, particularly among vulnerable populations. To address this public health issue, the FDA announced in April 2021 its intention to issue product standards banning menthol as a characterizing flavor in both cigarettes and cigars within a year. However, the public health benefits of these product standards may be attenuated by the role of plausible substitutes available in the marketplace What this study addsIn this randomized cross-over design study that included 80 adult menthol cigarette smokers, each of the alternative products demonstrated the ability to significantly reduce nicotine craving and withdrawal symptoms, but the combination of mentholated pipe tobacco and tubes in a menthol roll-your-own cigarette, resulted in the highest behavioral economic demand and positive subjective experience. How this study may affect policyTo maximize the benefits of a menthol cigarette ban, restrictions should extend to plausible substitutes, particularly menthol pipe tobacco and cigarette tubes.

IntroductionE-cigarette use among youth and young adults remains of public health concern. Pod-based e-cigarettes, including JUUL, significantly changed the e-cigarette landscape in the United States (US). Using an online survey, we aimed to explore the socio-behavioral correlates, predisposing factors, and addictive behaviors among young adult pod-mod users within a University in Maryland, USA. Methods112 eligible college students aged 18-24 years recruited from a University in Maryland who reported using pod-mods were included in this study. Participants were categorized into current/non-current users based on past-30-day use. Descriptive statistics were used to analyze participants responses. ResultsOf the 112 participants with mean age 20.5{+/-}1.2 years, 56.3% were female, 48.2% White, and 40.2% reported past-30-day (current) use of pod-mods. The mean age of first experimentation with pod-mods was 17.8{+/-}1.4 years, while the mean age of regular use was 18.5{+/-}1.4 years, with the majority (67.9%) citing social influence as the reason for initiation. Of current users, 62.2% owned their own devices, and 82.2% predominantly used JUUL and menthol flavor (37.8%). A significant proportion of current users (73.3%) reported buying pods in person, 45.5% of whom were below the age of 21. Among all participants, 67% had had a past serious quit attempt. Among them, 89.3% neither used nicotine replacement therapy nor prescription medications. Finally, current use (adjusted odds ratio (aOR):4.52; 95%CI:1.76,11.64), JUUL use (aOR:2.56; 95%CI:1.08,6.03), and menthol flavor (aOR:6.52; 95%CI:1.38,30.89) were associated with reduced nicotine autonomy, a measure of addiction. ConclusionOur findings provide specific data to inform the development of public health interventions targeted at college youth, including the need for more robust cessation support for pod-mod users.

ObjectiveTo systematically review and meta-analyse evidence regarding the efficacy of electronic nicotine delivery systems (ENDS) as smoking cessation aids. Data SourcesPubMed, Scopus, Web of Science, PsycINFO, MEDLINE and Cochrane Library were searched up to February-March 2020 (PROSPERO registration CRD42020170692). Study selectionPublished peer-reviewed randomised controlled trials (RCTs) of the efficacy of ENDS for sustained cessation of combustible tobacco smoking and/or nicotine use, compared with no intervention, placebo or nicotine replacement therapy (NRT) by intention-to-treat, with a minimum of four months follow-up. Data ExtractionData were extracted independently into a pre-specified template. Risk of bias was assessed with the Cochrane Collaborations tool and evidence quality rated using GRADE. Data SynthesisFrom 3,973 titles identified, nine RCTs were identified; 330 of 5,445 smokers randomised quit. Smoking cessation did notPublic health consequences differ significantly for randomisation to ENDS versus: no intervention (three studies, random-effects meta-analysis RR 1.95; 95%CI 0.90-4.22); placebo (three studies, 1.61; 0.93-2.78) or NRT (three studies; 1.25; 0.74-2.11). Fixed-effects sensitivity analyses showed significant results for ENDS vs NRT (1.43; 1.10-1.86). Smokers randomised to ENDS were substantially more likely than control to use nicotine at follow-up. Overall evidence quality was low. Considering only studies without potential competing interests further limited evidence but did not materially change conclusions. ConclusionsThere is insufficient evidence that ENDS are efficacious for smoking cessation compared to no intervention, placebo or NRT. Results are promising, particularly for therapeutic use, but vary according to analytic method. ENDS may lead to greater ongoing nicotine exposure than other smoking cessation methods. ImplicationsThis systematic review and meta-analysis consolidates current evidence on the efficacy of ENDS as an aid to sustained smoking and nicotine cessation and considers these findings in the context of potential competing interests. While findings are promising more research - preferably independent of industry funding - is needed to provide robust evidence of the efficacy of ENDS for smoking cessation. Future research should investigate nicotine cessation in addition to smoking cessation.

IntroductionLongitudinal surveys provide data to estimate transition probabilities between cigarette smoking, e-cigarette use, and dual use of both, facilitating projections of future use and the impact of policies. MethodsWe fit a continuous time Markov multi-state model for youth (ages 12-17y) and adults ([&ge;]18y) in Waves 1-4.5 of the Population Assessment of Tobacco and Health (PATH) longitudinal survey and estimated smoking and e-cigarette transition frequencies, including initiation, cessation, and relapse. We validated transition frequency results in a microsimulation model by projecting smoking and e-cigarette use prevalence over time. ResultsThere was more volatility in smoking and e-cigarette use among youth than among adults. For youth never smokers, annual smoking initiation among never/current/former e-cigarette users occurred in 0.4% (95% CI 0.2-0.6%)/8.8% (7.0-10.7%)/3.1% (2.1-4.2%), and current e-cigarette users were more likely to quit e-cigarettes than to initiate smoking (absolute difference in annual probability 46.5%, 38.7-54.2%). For adult current smokers, annual smoking cessation among never/current/former e-cigarette users occurred in 22.6% (20.9-24.3%)/14.5% (11.5-17.4%)/15.1% (12.1-18.2%). For adult current dual users, 14.5% quit smoking and 49.5% quit e-cigarettes annually. For adult former smokers, annual smoking relapse among never/current/former e-cigarette users occurred in 17.7% (15.8-19.6%)/29.3% (23.8-34.7%)/32.8% (27.1-38.6%). Using these transition probabilities in a microsimulation model accurately projected smoking and e-cigarette use prevalence at 12 and 24 months compared to PATH empirical data (root-mean-square error <0.7%). DiscussionPATH Waves 1-4.5 contain sufficient data to generate smoking and e-cigarette use transition frequency estimates for youth and adults in a microsimulation model. E-cigarette use among youth is especially volatile. IMPLICATIONSThis study estimates longitudinal transitions between nine cigarette smoking and e-cigarette use states among both youth and adults. Youth smoking and e-cigarette use was more volatile than that of adults. Smoking initiation, cessation, and relapse differed by e-cigarette use status, but it is not clear that e-cigarette use itself caused these differences. A tobacco and nicotine policy model parametrized with our estimates accurately predicted smoking and e-cigarette use prevalence over two years, enabling future work to project the outcomes and cost-effectiveness of policies targeting smoking and e-cigarette use.

Withdrawal StatementThe authors have withdrawn their manuscript owing to an issue, which they were recently alerted to, with GWAS of paternal smoking used here. They hope to update the manuscript with an alternative GWAS as soon as possible. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

IntroductionGraphic warning labels (GWLs) are widely employed to communicate smoking-related health risks; however, their implementation in the US has been held back by concerns about their efficacy. Most GWLs elicit a high level of emotional reaction (ER). The extent to which ER contributes to GWLs efficacy in improving smoking outcomes is a subject of debate. Our recent study showed poorer efficacy of the high-ER GWLs versus the low-ER ones during a month-long naturalistic exposure. Whether GWL effects persist after discontinuing the exposure remains unclear. MethodsWe conducted a secondary analysis to investigate the delayed effects of GWLs on smoking severity in adult smokers. The number of cigarettes smoked per day (CPD) was measured immediately as well as 4 weeks after the end of a month-long exposure to high-ER versus low-ER GWLs. Participants indicated their subjective feeling of being relieved from having to see the GWLs. ResultsWe found a significant reduction in CPD from the immediate to the 4-week post-exposure timepoint. There was no difference in CPD reduction between the high-ER and low-ER groups. Subjective sense of relief from GWL exposure was associated with greater CPD reduction in the high-ER group, but not the low-ER group. ConclusionsOur study suggests lasting impact of GWLs on smoking behavior. The findings may be particularly important to high-arousal GWLs, which appear less effective in reducing smoking during active exposure. ImplicationsWhether GWLs that evoke higher ER are more effective remains inconclusive. We recently showed that high-ER GWLs are less effective than low-ER ones in reducing smoking during continuous exposure. Here, we found evidence of delayed GWL effects such that smoking decreased from immediately to four weeks after the end of GWL exposure. Feeling of relief from GWL exposure was associated greater smoking reduction in the high-ER group. We suggest that continuously exposing smokers to high-ER GWLs that have been well remembered may be unnecessary and counterproductive.

The debate about electronic cigarettes has divided healthcare professionals, policymakers, and communities. Central points of disagreement are whether vaping electronic cigarettes are addictive and whether they produce major pulmonary complications. We developed a novel model of nicotine vapor self-administration in rats and found that rats voluntarily exposed themselves to nicotine vapor to the point of reaching blood nicotine levels that are similar to humans, exhibiting both addiction-like behaviors and cardiopulmonary abnormalities. The smoking cessation drug varenicline decreased electronic cigarette self-administration. These findings confirm the addictive properties and harmful effects of nicotine vapor and identify a potential medication for the treatment of electronic cigarette addiction.\n\nOne Sentence SummaryVaping nicotine-containing electronic cigarettes produces cardiopulmonary abnormalities, nicotine dependence and addiction-like behaviors, which are reduced by the smoking cessation drug varenicline.

Prenatal and early life exposure to cigarette smoke (CS) have repeatedly been shown to induce stable, long-term changes in DNA methylation (DNAm) in offspring. It has been hypothesized that these changes might be functionally related to the known outcomes of prenatal and early life CS exposure, which include impaired lung development, altered lung function and increased risk of asthma and wheeze. However, to date, few studies have examined DNAm changes induced by prenatal CS in tissues of the lung, and even fewer have attempted to examine the specific influences of prenatal versus early postnatal exposures. Here, we have established a mouse model of CS exposure which isolates the effects of prenatal and early postnatal CS exposures in early life. We have used this model to measure the effects of prenatal and/or postnatal CS exposures on lung function and immune cell infiltration as well as DNAm and expression of Cyp1a1, a candidate gene previously observed to demonstrate DNAm differences upon CS exposure in humans. Our study revealed that exposure to CS prenatally and in the early postnatal period cause long-lasting differences in offspring lung function, gene expression and lung Cyp1a1 DNAm, which wane over time but are reestablished upon re-exposure to CS in adulthood. This study creates a testable mouse model which can be used to investigate the effects of prenatal and early postnatal CS exposures and will contribute to the design of intervention strategies to mediate these detrimental effects.

Evidence from observational studies suggested that smokers are at increased risk of coronavirus disease 2019 (COVID-19). We aimed to assess the causal effect of smoking on risk for COVID-19 susceptibility and severity using two-sample Mendelian randomization method. Smoking-associated variants were selected as instrument variables from two largest genetic studies. The latest summary data of COVID-19 that shared on Jan 18, 2021 by the COVID-19 Host Genetics Initiative was used. The present Mendelian randomization study provided genetic evidence that smoking was a causal risk factor for COVID-19 susceptibility and severity. In addition, there may be a dose-effect relationship between smoking and COVID-19 severity.

IntroductionMonitoring trends in transitions in the use of electronic nicotine delivery systems (ENDS) and cigarettes among youth is important for understanding the potential public health impacts of these products. MethodsUsing a weighted Markov multistate transition model accounting for complex survey design, we estimated transition rates and one-year transition probabilities between never, non-current, ENDS-only, and cigarette use (with or without dual use of ENDS) among 26,744 youth aged 12-17 years who participated in at least two consecutive waves from Waves 2-7.5 (approximately 2015-2023) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. We also estimated transitions stratified by ages 12-14 and 15-17 years. ResultsThe one-year probability of ENDS-only initiation from never use among youth peaked in 2017-19 (Waves 4-5) at 4.0% (95%CI: 3.6-4.3%) and was higher for 15-17-year-olds at 5.8% (95%CI: 5.2-6.4%) than 12-14-year-olds at 2.2% (95%CI: 1.8-2.6%). In the following years, ENDS-only initiation rates declined and plateaued, with 2.6% (95%CI: 2.3-3.0%) initiation in 2022-23. Cigarette initiation from never use decreased over 2015- 23 from 0.8% (95%CI: 0.6-1.0%) in 2015-16 to 0.1% (95%CI: 0.0-0.2%) in 2022-23. There was an increase in the fraction of youth who transitioned from non-current product use to ENDS-only use from 13.7% (95%CI: 7.5-20.0%) in 2015-16 to 35.1% (95%CI: 25.4-44.8%) in 2022-23, paired with a decrease in non-current use to cigarette use from 20.9% (95%CI: 11.8-30.0%) to 6.3% (95%CI: 1.7-10.8%). Transitions from ENDS-only or cigarette use to non-current use remained relatively constant over time at around 25% and 15% per year, respectively. ConclusionENDS-only use initiation has changed over time, peaking around 2019 and subsequently decreasing and plateauing, but cessation rates for both ENDS and cigarettes have remained relatively stable. Thus, interruption of tobacco product initiation may be the most effective approach to reducing tobacco product use among youth. What this paper addsWhat is already known on this topic: O_LITransitions in cigarette and ENDS use have changed over time, with youth more likely to adopt ENDS and less likely to adopt cigarettes than older age groups. C_LI What this study adds O_LIWe found that ENDS initiation among youth peaked around 2019 and was higher for those 15-17 years than 12-14 years. There were few significant differences between the two age groups for other transitions. C_LIO_LICigarette initiation among youth declined over this period. Cessation rates for both ENDS and cigarettes have remained relatively stable. C_LI How this study might affect research, practice or policy O_LITobacco control efforts should prioritize preventing all tobacco and nicotine product initiation among youth. C_LI

BackgroundFactors influencing cessation include biopsychosocial characteristics, treatments and responses to treatment. The first cessation trial designed to assess cessation disparities between African American and White cigarette smokers demonstrated that socioeconomic, treatment, psychosocial and smoking characteristics explained cessation disparities. Ongoing translational efforts in precision cessation treatment grounded in genetically informed biomarkers have identified cessation differences by genotype, metabolism, ancestry and treatment. MethodsIn planned analyses, we evaluated six smoking-related measures, demographic and socioeconomic covariates, and prospective abstinence (7-day point prevalence at 12 weeks with bupropion, nicotine replacement and counseling treatments). We assessed concurrent and predictive validity in two covariate models differing by inclusion of Office of Management and Budget (OMB) race/ethnicity or genomic ancestry. ResultsWe studied Pharmacogenetic Study participants (N=456, mean age 49.5 years, 41.5% female, 7.4% African American, 9.4% Multiracial, 6.5% Other, and 6.7% Hispanic). Cigarettes per day (OR=0.95, P<.001), Fagerstrom score (OR=0.89, P<=.014), Time-To-First-Cigarette (OR=0.75, P<=.005) and predicted urinary nicotine metabolite ratio (OR=0.57, P<=.039) were associated with abstinence. OMB African American race (ORs from 0.31 and 0.35, p-values<=.007) and African genomic ancestry (ORs from 0.21 and 0.26, p-values<=.004) were associated in all abstinence models. ConclusionsFour smoking-related measures exhibited association with abstinence, including predicted nicotine metabolism based on a novel genomic model. African genomic ancestry was independently associated with reduced abstinence. Treatment research that includes social, psychological, treatment and biological factors is needed to reduce cessation disparities. ImplicationsO_LIThis is the first application of a statistical learning model of the urinary nicotine metabolite ratio to cessation. Results are concordant with biochemical and genetic models of the plasma nicotine metabolite ratio in multiethnic samples. C_LIO_LIThe urinary ratio exhibits the largest standardized effect size of four smoking-related measures associated with cessation (time-to-first cigarette, total Fagerstrom score and cigarettes per day were the others). C_LIO_LIThe social construct of African American race and genomic African ancestry are significant covariates in all cessation models. C_LIO_LIResults point to social and biological mechanisms requiring investigation in larger samples to understand and reduce cessation health disparities. C_LI

Background The clinical safety profile of e-cigarette use for smoking reduction remains poorly characterized. This study compared the relative safety and tolerability of nicotine e-cigarette use with non-nicotine e-cigarettes or a non-aerosol cigarette substitute (CS) among adults interested in reducing their smoking. Methods We conducted a secondary analysis of adverse events (AEs) reported in a 6-month, double-blind RCT involving 520 participants assigned to either e-cigarettes with 0, 8, or 36 mg/mL nicotine or a CS. AEs were coded using CTCAE V4.0 and assessed for frequency, severity, seriousness and relatedness across groups. Cumulative incidence was calculated over 24 weeks. We estimated risk differences (RDs) and 95% confidence intervals (CIs) for frequently reported AEs (>=1% of participants overall) comparing e-cigarette vs. CS and nicotine versus non-nicotine e-cigarette groups. Fisher's exact test, with adjustment for multiple comparisons, was used to assess statistical significance. Results Most study-related AEs (those rated as possibly, probably, or definitely related by medical monitor) were mild in severity and none were classified as serious. At 24 weeks, cumulative incidence of first study-related AE was highest in the 36 mg/mL (37.0%) and 8 mg/mL (35.2%) e-cigarette groups, followed by 0 mg/mL (23.4%), and lowest in CS group (2.5%). E-cigarette users experienced significantly greater risks of cough (RD [95%CI]: 8.5% [5.6-11.3]), headache (RD [95%CI]: 5.4% [3.3-7.6]) and sore throat (RD [95%CI]: 5.4% [3.2-7.6]) as compared with the CS group. Cough was also more common in those randomized to nicotine versus non-nicotine e-cigarettes (RD [95%CI]: 8.1% [3.4-12.8]). Conclusion All study products were generally well-tolerated; however, AEs were more common in e-cigarette groups, especially with nicotine. Findings highlight the need to monitor common symptoms such as cough, headache, and sore throat in clinical and regulatory evaluations of e-cigarette safety.

Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Cotinine supported self-administration and rats with a history of intravenous self-administration of cotinine exhibited relapse-like drug-seeking behavior, suggesting cotinine may also be reinforcing. To date, a potential contribution of cotinine to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1 enzyme in the rat and methoxsalen is a potent CYP2B1 inhibitor. The study tested the hypothesis that methoxsalen inbibits nicotine metabolism and self-administration, and that cotinine replacement attenuates the inhibitory effects of methoxsalen. Acute methoxsalen decreased plasma cotinine levels and increased nicotine levels following subcutaneous nicotine injection. Repeated methoxsalen reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, disruption of lever differentiation, smaller total nicotine intake, and lower plasma cotinine levels. On the other hand, methoxsalen did not alter nicotine self-administration during the maintenance phase despite great reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels, counteracted effects of methoxsalen, and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. These results indicate that methoxsalen depressed cotinine formation from nicotine and the acquisition of nicotine self-administration, and that replacement of plasma cotinine attenuated the inhibitory effects of methoxsalen, suggesting that cotinine may contribute to the development of nicotine reinforcement.

"Dry Hitting" is a unique phenomenon of e-cigarette use that has been shown to produce toxic chemical degradants and byproducts. Although it is widely understood that nicotine exposure during adolescence impacts neurobiological and behavioral function, little is known about how dry hitting may impact users. We hypothesized that subjects repeatedly exposed to nicotine dry hit vapor would exhibit distinct behavioral responses compared with saturated nicotine vapor and would differentially alter the expression of perineuronal nets (PNNs) in the rodent brain. Using a customized system of e-cigarette vapor inhalation, adolescent male Wistar rats (PND 31-40) received vaporized nicotine (30 or 60 mg/mL; [~]2.5-3 mL/cage), nicotine with dry hits (60 mg/mL; 1.75-2 mL/cage), or propylene glycol (PG) vehicle for 30 minutes over 7 daily sessions. Locomotor activity, antinociception, and elevated plus maze testing were used to assess behavioral response to drug intoxication and tolerance. Immunohistochemistry was used to identify Wisteria Floribunda Agglutinin (WFA)-positive PNN structures in the amygdala and insular cortex. Rats exposed to dry hits exhibited behavioral responses (locomotor sensitization, antinociception) similar to those of rats exposed to saturated nicotine vapor, but spent more time in the open arms of the elevated plus maze. Immunohistochemical analyses confirmed significantly greater WFA intensity in the central nucleus of the amygdala, but not the basolateral amygdala or insular cortex, of rats exposed to dry hits. Overall, these data confirm the impact of dry hit vapor on behavioral responses and perineuronal net expression in rats during adolescence.

IntroductionSmoking contributes a huge burden on public health; thus, identifying risk factors for smoking remains an important area of research. This study adds to the wealth of existing literature by utilising repeated smoking measures collected in a UK sample of young adults to (a) examine differences between longitudinal smoking behaviours, (b) investigate their association with many risk factors, and c) consider how these associations may change over time. MethodsThis study uses longitudinal latent class analysis and 12 repeated measures to derive patterns of smoking in the Avon Longitudinal Study of Parents and Children. The association of these patterns with 402 risk factor measures collected from 0-28 years is then investigated. The selected risk factors include familial and peer factors, lifestyle and sociodemographic factors, mental health, parenthood, adverse childhood experiences and trauma. ResultsFive different latent classes of smoking were derived and referred to as non-smoking, short-term smoking, occasional smoking, early-onset smoking, and late-onset smoking. These showed differences in age of onset, frequency, and cessation. Other substance use, and parental and peer substance use, showed the strongest association with smoking patterns. More risk factors were associated with early-onset than late-onset smoking. Many risk factors of regular smoking did not show the same associations with occasional smoking. Fewer measures differentiated late-onset from short-term smoking. Some associations varied depending on the time of measurement or smoking pattern in question. ConclusionsFindings from this study may be used to identify groups of people most vulnerable to more harmful smoking patterns despite being exposed to strong tobacco prevention efforts. This could also help better tailor smoking interventions and improve tobacco control policies.

BackgroundUnderstanding the relationship between electronic nicotine delivery systems (ENDS) use and chronic obstructive pulmonary disease (COPD) and other respiratory conditions is critical. However, previous studies have not adequately controlled for history of cigarette smoking. Research QuestionTo examine the prospective association between ENDS use and self-reported incident COPD after adjusting for cigarette smoking history. Study Design and MethodsUsing waves 1-5 of the US Population Assessment of Tobacco and Health (PATH) study, we examined the association between ENDS use and self-reported incident COPD among adults aged 40+ using discrete time survival models. Current ENDS use was measured as a time-varying covariate, lagged by one wave, defined as established daily or some days use. We controlled for baseline demographics (age, sex, race/ethnicity, education), health characteristics (asthma, obesity, exposure to second-hand smoke), and smoking history (smoking status and cigarette pack-years). ResultsIncident COPD was self-reported by 925 respondents during the five-year follow-up period. Prior to adjusting for other covariates, time-varying ENDS use appeared to nearly double the risk of incident COPD (HR 1.98, 95% CI 1.44-2.74). However, ENDS use was no longer significantly associated with COPD (aHR 1.10, 95% CI 0.78-1.57) after adjusting for current cigarette smoking and cigarette pack-years. The risk of self-reported incident COPD increased with cigarette pack-years and was higher for respondents who were older, female, less educated, and had baseline asthma or obesity. InterpretationENDS use did not significantly increase the risk of self-reported incident COPD over a five-year period once current smoking status and cigarette pack-years were taken into account. Cigarette pack-years, on the other hand, remained associated with a net increase in the risk of self-reported incident COPD. These findings highlight the importance of using prospective longitudinal data and properly controlling for cigarette smoking history to assess the independent health effects of ENDS.

BackgroundConcerns have been raised that e-cigarettes have created a new generation of people addicted to nicotine. This study aimed to examine changes in the proportion of US high-school students reporting symptoms of nicotine dependence over the past decade, in the context of changing patterns of nicotine product use. MethodsRepeat cross-sectional analyses of a nationally-representative sample of 107,968 US high-school students (14-18y) participating in the 2014-2023 National Youth Tobacco Surveys. Nicotine product use was categorised based on self-reported past-30-day use of cigarettes, other combustible tobacco, smokeless/non-combustible products, and e-cigarettes. Nicotine dependence was operationalised as (i) strong past-30-day cravings to use tobacco and (ii) wanting to use nicotine products within 30 minutes of waking. ResultsPast-30-day use of any nicotine product decreased from 24.5% [22.5-26.6%] to 19.6% [16.8-22.4%] between 2014 and 2017, increased sharply reaching 31.4% [29.0-33.7%] in 2019, then fell to the lowest level at 12.5% [10.9-14.1%] by 2023. The proportion who reported symptoms of nicotine dependence was substantially lower, but followed a similar pattern of changes over time. For example, the proportion reporting strong cravings decreased from 7.8% [6.6-9.0%] to 5.5% [4.3-6.7%] between 2014 and 2017, increased to 7.9% [6.8-9.0%] between 2017 and 2018 and remained stable up to 2020, then fell to the lowest level at 2.5% [1.9-3.1%] by 2023. Use of cigarettes fell considerably across the period (from 9.0% [7.9-10.3%] to 1.8% [1.4-2.4%]); this was the product category consistently associated with the highest levels of dependence. The proportion using only e-cigarettes increased rapidly between 2017 and 2019 (from 5.4% [4.2-6.8%] to 17.0% [15.3-18.7%]) then fell to 6.7% [5.6-7.9%] by 2023; symptoms of nicotine dependence within this group increased non-linearly over time with increases through to 2022 before possible declines in 2023. ConclusionsThe sharp rise in the prevalence of nicotine product use (in particular, e-cigarettes) among US high-school students in the late 2010s was short-lived and was not accompanied by a sustained increase in the overall population burden of nicotine dependence. By 2023, both nicotine product use and nicotine dependence had reached historic lows.

ObjectivesMenthol flavoring is a critical public health issue, but prior work has largely represented the voices of White adults who smoke (AWS) menthol cigarettes who comprise a small subset of AWS menthol cigarettes in the US. This study compared perceptions of a hypothetical MC/FC ban among Black and White AWS menthol cigarettes. MethodsParticipants were a convenience sample of 2,113 Black and 1,087 White AWS menthol cigarettes collected through Amazon Mechanical Turk between July 2023 and January 2024. Participants reported opinions about a MC/FC ban, likely public health outcomes, and hypothetical impact of the ban on their smoking behavior. Stepwise logistic regression modeled factors associated with ban opposition/ambivalence. ResultsOver one-third of menthol cigarette users supported a MC/FC ban (Black, 37.2% vs White, 34.5%, p=.13], but Black AWS were more likely to endorse public health benefits of a ban assessed via agreement with 5 statements of FDA rationale [3.0 (SD=1.7) versus 2.4 (SD=1.8), p<.001]. Smoking more cigarettes per day, belief that menthol cigarettes are more addictive/harder to quit, and intent to continue using nicotine under a ban increased odd of opposition/ambivalence. ConclusionsCompared to White AWS, Black AWS were more likely to believe that a MC/FC ban would benefit public health and showed no statistical difference in overall support for a ban. Targeted outreach to those who consume more menthol products and those who do not intend to quit nicotine could increase ban support among menthol users. Summary Box1) What is the current understanding of this subject?Knowledge of the publics perception of a MC/FC ban is largely informed by White menthol cigarette users. Given that Blacks represent the majority of AWS menthol cigarettes in the US, the paucity of data from Black voices engenders a critical gap in research used to inform health policy. 2) What does this report add to the literature?Compared to White AWS, Black AWS were more likely to believe that a MC/FC ban would benefit public health and showed no statistical difference in overall support for a ban. To our knowledge, this study comprises the largest convenience sample of perceptions and perceived impact of a federal MC/FC product standard among Black AWS menthol cigarettes in the US and provides valuable evidence to inform policy action in these areas. 3) What are the implications for public health practice?Findings support ongoing efforts to advance a MC/FC product standard and suggest that targeted outreach to those who consume more menthol products and those who do not intend to quit nicotine could increase ban support among menthol users.