Nicotine & Tobacco Research

Short-form video platforms increasingly shape how young audiences encounter health information. Generative artificial intelligence can produce standardized avatar-based messages at scale, but randomized evidence for tobacco prevention is scarce. In this three-arm randomized online intervention study with pre-post assessment, participants aged 16 years or older were assigned to an AI avatar video emphasizing short-term smoking consequences, an AI avatar video presenting long-term cancer-related information matched to an American Cancer Society fact sheet, or the same fact sheet in written form. The primary outcome was post-intervention intention to avoid smoking and secondhand smoke exposure, adjusted for baseline intention. Among 400 randomized participants, 272 had complete data for the primary baseline-adjusted analysis. Intention increased from baseline to post-intervention in all conditions, with no statistically significant between-group differences. These findings support AI avatar videos as a scalable, social-media-compatible format for digital tobacco prevention, while not establishing superiority or equivalence.

Background: Loneliness and social isolation may contribute to tobacco and nicotine use, but existing studies have been inconsistent. This systematic review and meta-analysis examined these associations among adults amid the evolving nicotine product landscape. Methods: A systematic search of PubMed, MEDLINE, PsycINFO, and CINAHL identified peer-reviewed quantitative studies published between 2014 and 2025 searched in February-April 2026. Eligible studies included adults aged [≥]18 years examining loneliness and/or social isolation in relation to smoking or nicotine use. Two reviewers independently screened studies, extracted data, and assessed risk of bias (using the National Heart, Lung, and Blood Institute risk of bias tool). Random effects meta-analyses were conducted to estimate pooled odds ratio (OR) with 95% confidence intervals (CIs). Results: 22 studies involving 273,954 participants met inclusion criteria, and 14 studies were included in the meta-analysis. A majority of the studies had low risk of bias. Meta-analysis findings showed that social isolation or loneliness was associated with significantly higher odds of nicotine product use (OR 1.84, 95% CI 1.48-2.29). Although no statistically significant association of nicotine product use and social isolation or loneliness (OR 1.35, 95% CI 0.72-2.53), some studies suggested bidirectional relationships, with smoking contributing to reduced social support and greater isolation over time. Sensitivity analysis showed the robustness of the meta-analysis findings. Subgroup analysis found no statistically significant differences were seen between subgroups defined by type of nicotine product, age groups, social isolation vs loneliness, measures of nicotine use behaviours and pre- vs post- COVID-19 pandemic period in the meta-regression. Limitations of included studies and analysis are discussed. Conclusions: Loneliness and social isolation are significant psychosocial correlates of nicotine product use. Cessation interventions may benefit from integrating social support and mental health strategies alongside traditional nicotine dependence treatment.

BackgroundObservational comparisons of former smokers who use non-combusted nicotine products with former smokers who quit without them require that two quantities be measured precisely: which product is being used, and how long ago cigarette smoking stopped. Neither quantity is recorded by the National Health Insurance Service (NHIS) screening instrument used in a recent Korean cohort study of post-cessation e-cigarette use and lung cancer risk. We characterized both quantities in a contemporaneous, nationally representative survey of the same population. MethodsWe analyzed the public-release microdata of the Korea National Health and Nutrition Examination Survey (KNHANES), 2018 to 2023, restricted to adults aged 19 years and older. Former smokers were identified by smoking status, and cessation duration was taken from the item recording months since the last cigarette. Former smokers currently using a heated tobacco product (HTP) or an e-cigarette (EC) were compared with former smokers using neither. KNHANES 2018 asked a generic e-cigarette question and, separately, a checklist naming HTP brands, allowing the two product classes to be separated. Distributions were compared with rank-based methods, the age-duration relationship with Theil-Sen regression, and residual imbalance by restricting the comparison group to respondents age-matched to within two years. ResultsThe 2018 analytic sample comprised 1,348 former smokers, of whom 43 currently used HTP or EC and 1,305 used neither. Among the product-using former smokers, 58% reported HTP use without e-cigarette use, 21% reported both, and 21% reported e-cigarette use without HTP use; 79% reported any HTP use. Median cessation duration was 0.7 years (IQR 0.25 to 1.5) among product users and 12.0 years (IQR 5.0 to 20.0) among those using neither (Kolmogorov- Smirnov D = 0.76, P < 0.001), with the product user having quit more recently in 92% of cross-group pairs. The separation persisted within the short-term (<5 year) stratum (D = 0.34, P < 0.001; 73% of pairs) and after age matching, where the residual gap was 9.3 years. Cessation duration rose with age among those using no product (Theil-Sen slope +0.30 years per year) but was flat among product users (-0.01). Restricting to the screening-eligible stratum used in the cohorts high-risk analysis did not attenuate the imbalance: among those aged 50 to 80, median cessation among no-product quitters rose to 15.5 years (n = 858), and adding a 20 pack-year criterion left 421 no-product quitters with a median of 11.0 years against three HTP/EC users who had quit 0.25, 1.0 and 2.0 years earlier, despite closely matched cumulative exposure (mean 37.6 vs 37.7 pack-years). The overall contrast reproduced in every wave from 2018 to 2023, with an age-matched residual of 9 to 11 years. ConclusionsIn a nationally representative survey of the same population and the same calendar year as the NHIS screening cohort analyzed by Kim et al., Korean former smokers using non-combusted nicotine products differed from other former smokers in two respects that bear directly on how such comparisons should be read. First, they were predominantly HTP users: 79% reported any HTP use, and only 21% reported e-cigarette use without HTP use. Second, they had stopped smoking approximately a decade more recently, a difference that survived stratification at five years and exact age matching. Neither quantity is recorded in the NHIS screening instrument. Cohort estimates comparing post-cessation product users with other quitters should therefore be interpreted with caution if they do not precisely characterize product composition and to time since cessation, and future studies should measure both directly.

Introduction: Nicotine Pouches are increasingly used as a smokeless alternative to cigarettes and other nicotine products, yet their acute cardiovascular effects remain poorly documented. While nicotine's impact on heart rate and electrocardiogram (ECG) parameters is well-documented in smoking, no trials have evaluated these effects specifically for nicotine pouches. Methods: This study is a single-center, double-blind, placebo-controlled, crossover trial which will include 20 healthy adult nicotine users. Participants will undergo three sessions, receiving either a placebo, 6 mg, or 14 mg nicotine pouch in random order. Heart rate obtained by an ECG and various other ECG parameters, vital signs, and subjective symptoms will be measured at baseline, and multiple time points over 30 minutes. Conclusions: This study aims to determine whether nicotine pouches cause acute changes in heart rate, ECG parameters, vital signs, and self-reported symptoms. We hypothesize that higher nicotine pouch does will lead to measurable increases in heart rate and other autonomic effects compared to placebo.

Background and Aims: Anxiety remains prevalent among adolescents while tobacco and nicotine product use, especially the recent increases of novel product use such as e-cigarettes and nicotine pouches, raises further public health concerns. The associations between novel tobacco and nicotine product use and anxiety remains understudied. This study aims to determine whether tobacco and nicotine product use is associated with generalised anxiety and whether this association differs by used product. Design: Cross-sectional survey, School Health Promotion study in 2025. Setting: A school-based nationwide survey conducted in all Finnish lower and upper secondary schools. Participants: Students aged 13-20 years in three school levels: 8.-9. grade students in lower secondary schools (N= 94 743, 73% of the students), 1st and 2nd-year students in general upper secondary schools (n=47 248, 70% of the students) and of vocational institutions (n=24 998, 38% of the students). Measurements: Exclusive (single product) and non-exclusive ([&ge;]1 products) daily or weekly use of tobacco and nicotine products, including nicotine pouches, e-cigarettes, cigarettes, and smokeless tobacco (snus). Generalised anxiety was measured using the Generalised Anxiety Disorder Scale (GAD-7). The cut-off of >10 points indicated participants with moderate to severe self-reported generalised anxiety symptoms. Background variables included sociodemographic variables and heavy drinking. Results: Of the 166,989 participants 51.4% were females, mean age was 15.7 (SD 1.27), 21.2% reported generalised anxiety. Prevalence of generalised anxiety increased gradient-wise in accordance with both non-exclusive and exclusive use frequency of different tobacco and nicotine products, as well as with number of products used. Daily use of nicotine pouches was associated with higher odds of anxiety compared with never use (boys: adjusted odds ratios (aOR) 1.19, 95% CI, 1.05 to 1.34; girls: aOR 1.74, 95% CI, 1.58 to 1.91), yet the association between daily e-cigarette use seemed to be stronger (boys aOR 1.96, 95% CI, 1.54 to 2.49; girls: aOR 2.29, 95% CI, 2.09 to 2.51). Summary: Any use of tobacco and nicotine products, including new products, is associated with generalised anxiety among adolescents, with some differences between products. Measures to prevent the initiation of tobacco and nicotine product use and to promote mental health among adolescents should be enacted.

Background: Smoking inequalities by socioeconomic status have widened consistently in Germany, but sex-specific trends after 2013 and inequalities in daily cigarette consumption among smokers (intensity) are unknown. We analyzed trends in absolute and relative socioeconomic inequalities in smoking prevalence and intensity among German adults across three decades. Methods: We used 14 waves (1998-2024) of population-representative cross-sectional data from the German Socio-Economic Panel to estimate sex-specific trends in smoking prevalence and intensity in adults aged 25-64. Inequalities were quantified across strata of education, occupation, and equivalized household income using the absolute and relative concentration index with 95% bootstrap confidence intervals. Results: Overall smoking prevalence declined from 35.05% (CI: [33.90%, 36.20%] in 1998 to 22.19% (CI: [21.15%, 23.24%]) in 2024, and mean intensity from 17.49 (CI: [17.09,17.90]) to 13.33 (CI: [12.88, 13.79]) cigarettes/day. Over this period sex-differences in both outcomes narrowed almost completely. Absolute and relative inequalities in smoking prevalence widened across all SES dimensions, particularly for education and occupation. By 2024, inequalities were larger among women than men driven by a stagnating or rising smoking prevalence among low-SES women at least until 2018 alongside continued declines in higher-SES women and for men. Inequalities in smoking intensity, particularly related to income, were generally smaller than those in prevalence. Conclusion: Socioeconomic smoking inequalities in Germany widened from 1998 to 2024 primarily driven by reductions among higher-SES groups and increases in low-SES women. However, recent reductions in low-SES women may indicate a new phase in the smoking epidemic. Health equity considerations should be integrated into a targeted German tobacco control strategy.

Background Mandatory reductions in tobacco product nicotine content to non-addictive levels may help achieve a tobacco endgame. Evidence exists for potential positive impacts of 'very low nicotine content' (VLNC) cigarettes in promoting smoking cessation in trial settings, but the population-level policy impact is unknown. Methods An online expert knowledge elicitation survey was undertaken to generate estimates for the impact of a VLNC mandate in Australia. Global experts in tobacco control were recruited to individually estimate impacts on smoking initiation, cessation, and switching to e-cigarettes or illicit market cigarettes. Linear pooling was used to estimate a combined (non-parametric) distribution per question, incorporating minimum, maximum, and best guess values from each respondent. Results The survey was completed by 15 experts. Interquartile ranges from pooled responses indicated that in the first year of a VLNC policy, smoking cessation could increase by 1.2-7.1 times the rate without the policy and switching to vaping by 1.3-8 times. Switching to illicitly supplied 'normal' nicotine cigarettes was estimated between 15-50% of those who smoke. Smoking initiation estimates varied greatly. Experts from Australia (n=8) consistently reported lower estimates for positive outcomes, and higher illicit market switching estimates, than experts from other countries. Conclusions Given the absence of implementation evidence, this study provides Australia-specific estimates of the potential behavioural effects of a VLNC policy. The findings suggest that denicotinisation would accelerate declines in smoking, but that it may be undermined by illicit cigarette access in Australia. Estimates should be updated with real-world evidence as it becomes available.

Introduction The Tobacco and Vapes Act 2026 provides the UK government powers to ban vaping in public places. Proposals include extending existing indoor smoke-free legislation to also being vape-free and making public children's playgrounds and outdoor areas of education settings vape-free. We examined adults' and adolescents' views on vape-free places. Methods Two UK-wide cross-sectional online surveys were conducted in 2026, one with adult (18+) current and former nicotine users (n=2,851), and one with adolescents aged 11-17 years (n=2,123). We measured (1) perceived acceptability of vaping in public places, (2) views on whether vapes should/should not be allowed in public places, and (3) perceived likelihood of public compliance with vaping bans. Results Adults considered it unacceptable to vape on public transport (85.9%), on school grounds (outdoors) (83.6%), outside hospital entrances (59.2%), and inside pubs (57.8%) and nightclubs (52.5%). A minority considered it unacceptable to vape at open air playparks (40.6%). Most adolescents viewed vaping as unacceptable in all locations. Perceived acceptability of vaping in each place was associated with current vaping and/or smoking. Adults and adolescents believed vaping should not be allowed on public transport (88.9%; 93.8%) or outdoors on school grounds (85.8%; 93.5%). Adults and adolescents perceived likely compliance on public transport, school grounds and in pubs, but not in nightclubs, outside hospital entrances and at open air playparks. Conclusion The findings indicate public support for some vape-free places among adults and adolescents, particularly on public transport and school grounds, and less so for a ban at open air playparks.

Introduction Smoking prevalence remains higher in rural than in urban populations in the United States. To examine recent trends, we assessed state-level differences in cigarette smoking between urban and rural areas from 2018 to 2024. Methods Using repeated cross-sectional data from the Behavioral Risk Factor Surveillance System, we estimated state-specific logistic regression models to examine the relationship between urban-rural county residence and cigarette smoking. Unadjusted models (model 1) included urban-rural county status and year. Subsequent models (model 2) added age, sex, and race/ethnicity. A final model (model 3) included education and an interaction term between urban-rural county status and year to examine whether gaps in urban-rural smoking changed over time. In states with significant interactions, simple effects tests compared trends for urban-rural groups separately. Results Compared to urban adults, rural adults had higher unadjusted odds of cigarette smoking (odds ratio [OR] range:1.07-1.88) in 88.4% (38/43) of states. Adjusting for demographic covariates (model 2) increased the proportion of states with significant marginal effects of rurality to 90.7% (ORs:1.09-1.87). A final model that also controlled for education (model 3) decreased the proportion of states with significant marginal effects of rurality to 60.5% (ORs:1.10-1.54). Among the 14 states with significant interaction terms, the odds of smoking declined faster among urban than rural residents. Conclusion Urban-rural differences in smoking persist across most states. No state showed a reduction in urban-rural disparities over time, and the urban-rural gap widened in 14 states. Demographic variation accounted for some, but not the majority, of observed urban-rural differences.

Aims To estimate the prevalence of past-year smoking quit attempts in Great Britain and examine variation by sociodemographic and socioeconomic characteristics, mental health, alcohol use, smoking-related characteristics, and geographic area. Design Cross-sectional analysis of data from a nationally representative household survey (the Smoking Toolkit Study) conducted October 2020 to May 2026. Setting Great Britain. Participants 24,786 adults ([&ge;]18y) who reported past-year tobacco smoking. Measurements The outcome was self-reporting having made at least one serious attempt to stop smoking in the previous 12 months. Associations with age, gender, ethnicity, social grade, health-related economic inactivity, mental health conditions, psychological distress, alcohol consumption, use of non-combustible nicotine, cigarette type and consumption, strength of urges to smoke, and motivation to stop smoking were assessed. We calculated weighted prevalence estimates and odds ratios (ORs) adjusted for survey year. Findings Overall, 36.7% [95%CI=36.0-37.4] of adults who had smoked in the past year self-reported making at least one quit attempt. Annual prevalence was relatively stable over the study period (range: 35.5% [33.9-37.1] to 37.6% [35.9-39.3]). Making a past-year quit attempt was more common among younger adults (48.0% among 18-24-year-olds) and declined progressively with age (24.6% among [&ge;]65-year-olds; OR=0.35, 95%CI=0.31-0.39). Compared with White adults, making a past-year quit attempt was more common among Black (OR=1.31, 1.11-1.55) and Asian (OR=1.40, 1.21-1.62) adults. Adults with a history of diagnosed mental health conditions (OR=1.27, 1.17-1.38) and moderate (OR=1.31, 1.20-1.43) or severe psychological distress in the past month (OR=1.39, 1.25-1.56) had greater odds of reporting a past-year quit attempt than those without. Those reporting increasing/higher risk alcohol consumption had lower odds than non-drinkers (OR=0.88, 0.82-0.95). Current use of nicotine replacement therapy (OR=2.59, 2.36-2.83) and vapes (OR=2.15, 2.02-2.30) were positively associated with reporting a past-year quit attempt. Odds were lower among those with greater cigarette consumption (OR range 0.79-0.86 among those smoking >10 vs. [&le;]5 cigarettes per day). Motivation to stop smoking showed the strongest gradient (OR range 2.95-29.09). Geographic differences were modest, with prevalence ranging from 32.1% [29.9-34.3] in Wales to 39.4% [35.9-43.1] in North East England. Conclusions Between 2020 and 2026, around one in three adults in Great Britain who smoked in the past year reported making a serious attempt to quit, corresponding to approximately 3.5 million people annually. Making a past-year quit attempt was more strongly associated with smoking-related factors than sociodemographic characteristics.

Background: The prevalence of cannabis use is increasing at an alarming rate owing to its legalization and decriminalization in some countries. Epidemiological evidence on the association between cannabis use and cancer is inconsistent and conflicting. Herein, we performed two-sample Mendelian randomization (MR) to investigate whether cannabis use is causally associated with site-specific cancers in individuals of European ancestry. Methods: We identified 22 independent genetic variants strongly associated with cannabis use (p-value < 5 x 10-8) in a large meta-analysis of genome-wide association studies of individuals of European ancestry. Genome-wide association summary-level data on site-specific cancers were obtained from individuals of European ancestry in FinnGen, Finland. MR analyses were performed using the inverse-variance weighted (IVW) and multivariable method. Sensitivity analyses were performed using the simple median, weighted median, MR-Egger, and MR pleiotropy residual sum and outlier methods. Results: Our multivariable IVW analyses adjusted for cigarette smoking found that genetic liability to cannabis use was causally associated with esophageal cancer (odds ratio [OR] =1.74, 95% confidence interval [CI] =1.29-2.15, p-value =0.013) and lung cancer (OR=1.35, 95% CI = 1.13-1.58, p-value =0.009). However, genetic liability to cannabis use exerted a protective effect against pancreatic cancer (OR=0.77, 95% CI =0.57-0.91, pvalue=0.032) in individuals of European ancestry in the FinnGen. Our sensitivity analyses found no evidence of horizontal pleiotropy between cannabis use and site-specific cancers. Conclusion: We found that genetic liability to cannabis use was associated with esophageal, lung, and pancreatic cancers in individuals of European ancestry.

Introduction: Childrens exposure to second hand tobacco smoke is a preventable global public health issue, yet there is no consensus on how best to support families to create a smoke free home. This pilot randomised controlled trial tested the feasibility of use of free nicotine replacement therapy combined with telephone delivered support to reduce childrens exposure to second hand smoke in the home, and inform a future full scale trial. Methods: Parents and carers aged 18 and over, who smoke in the home and care for one or more children aged 0 to 16 years were recruited through existing initiatives and social media. Participants were randomised to either the intervention or control arm. Group A received free posted to home nicotine replacement therapy, alongside fortnightly telephone calls to support smoking abstinence in the home. Group B were signposted to the Scottish Government Take it Right Outside website which provides interactive advice on creating a smoke free home. To measure second-hand smoke levels, participants installed an air quality monitor in their living room for 7 days to measure fine particulate matter at baseline and 12 week follow-up. Results: Approximately one-quarter (27 of 100) of the intended sample size was recruited. Median fine particulate matter concentrations reduced in both the intervention (by 36mg per cubic metre) and control (by 16mg per cubic metre) groups. Retention rates and adherence rates to nicotine replacement therapy were 70 percent and above, with no risks and or safety concerns reported, suggesting this approach is feasible and acceptable to participants. The estimated cost of delivering this 12 week intervention was two hundred and forty four pounds per individual. Conclusions: Although recruitment rates were insufficient to recommend progression to a larger trial to test effectiveness of this approach in Scotland, this study could inform trial development in other countries where smoking in the home is commonplace. Insights regarding the alignment of smoke free home interventions with broader smoking cessation initiatives could inform future policy and public health approaches.

Tobacco control treaties were written for billboards and television, not for the people now selling lifestyles to young Africans. As mobile internet saturates East African cities, social media influencers have become an unmeasured channel, especially when it comes to tobacco promotion. We assessed the prevalence of tobacco use, its association with influencer exposure, and how urban youth interpret that exposure in two capitals with different tobacco laws. We conducted a comparative mixed-methods study among youth aged 18-29 years in Kampala, Uganda, and Nairobi, Kenya (January-August 2025), combining (i) a cross-sectional survey using systematic sampling at youth-dense venues (n=772), (ii) four online focus group discussions (FGDs; n=40), and (iii) content analysis of 30 tobacco-related posts from high-reach influencers (greater than 50,000 followers). We used chi-square tests and multivariable logistic regression, thematic analysis (Braun and Clarke), and descriptive engagement metrics. Ever tobacco use among urban youth in East Africa was 29.3% (226/772), similar in Kampala (30.7%) and Nairobi (28.0%; p=0.409). After adjustment, exposure to influencers promoting tobacco independently predicted ever use (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.29-2.82; p=0.001), alongside male sex (aOR 2.35) and age 26-29 years (aOR 1.99). Tertiary education (aOR 0.45) and never seeing tobacco content (aOR 0.26) were protective. Posts framed tobacco as aspirational lifestyle; 77% of sampled comments were positive and 47.5% expressed interest in trying the product. Influencer exposure behaved as a modifiable risk factor of a magnitude comparable to established demographic drivers. Tobacco control in the region must move from print-era advertising bans to platform governance, mandatory disclosure of paid promotion, and youth-led counter-marketing.

Objective: To examine changes in vaping and smoking trends following the announcement and implementation of the disposable vape ban in Great Britain. Design: Interrupted time-series analysis of representative monthly cross-sectional data from the Smoking Toolkit Study. Setting: Great Britain. Participants: 118,946 adults ([&ge;]16y), including 12,042 young adults (16-24y), surveyed between Jan-2022 and Feb-2026. Main outcome measures: Changes in trends in disposable vape use among vapers, and current vaping and smoking prevalence, using seasonally-adjusted generalised additive models with comparisons against a no-ban counterfactual in which pre-announcement trends continued unchanged. Results: The proportion of vapers mainly using disposable devices began to decline following the announcement of the ban in Jan-2024, with the fall accelerating after implementation in June-2025. By Feb-2026, 5.6% (95%CI 4.6-6.9) of adult vapers and 7.1% (5.1-10.1) of young adult vapers mainly used disposables, compared with 62.0% (53.6-71.8) and 63.6% (52.7-76.7), respectively, under a no-ban counterfactual. Increases in vaping prevalence slowed post-announcement and plateaued post-implementation; by Feb-2026, prevalence was lower than the no-ban counterfactual in adults (13.6% v 18.8%; difference -5.2 percentage points, 95%CI -7.1 to -3.3) and young adults (27.8% v 39.1%; -11.3, -18.6 to -4.1). Declines in smoking prevalence stalled among adults and reversed among young adults post-announcement, before shifting downward again post-implementation; by Feb-2026, smoking prevalence was similar to the no-ban counterfactual in adults (difference +0.9 percentage points, -0.5 to +2.2) but possibly higher in young adults (+3.3, -0.5 to +7.1). Conclusions: The disposable vape ban in Great Britain was associated with substantial changes after both announcement and implementation, including a marked reduction in disposable vape use and a slowing then plateauing of growth in overall vaping prevalence. However, declines in smoking also temporarily slowed--and among young adults, reversed--after the announcement, before downward trends resumed after implementation.

Background: In the United States, several states have restricted sales of flavoured tobacco products, including popular menthol- and mint-flavoured Oral Nicotine Pouches (ONP). In response, tobacco companies introduced "unflavoured" ONP containing odorless synthetic cooling agents. Since these, in turn, have become targets of legislative bans, the tobacco industry may seek out flavourants with other sensory effects to increase the appeal of "unflavoured" ONP. Methods: Online merchants were searched for "unflavored" ONP marketed to consumers in jurisdictions with flavour bans. Sensory effects of aqueous extracts from identified "heat", "spicy" and "unflavoured" ONP were analyzed by Ca2+ microfluorimetry in HEK293 cells expressing the human heat/chili pepper flavourant (capsaicinoid) receptor, hTRPV1. ONP were analyzed for capsaicinoids and sweeteners by Liquid Chromatography/Mass Spectrometry (LC/MS). Results: A new category of "heat" or "spicy" ONP was identified, including products marketed as "unflavoured". Extracts from all these ONP robustly activated TRPV1, with "unflavoured" Lucy Heat the most potent. Chemical analysis demonstrated that Lucy Heat contained the synthetic capsaicinoid nonivamide at high levels (~675 microgram/pouch), while others contained mixtures of capsaicinoids (5-25 microgram/pouch) combined with other characterizing flavours (tropical, fruit). All tested ONP contained sweeteners. Conclusions: The tobacco industry continues to probe regulatory loopholes by claiming that newly introduced capsaicinoid flavourants and sweeteners in ONP do not represent characterizing flavours. This is contradicted by industry and regulatory determinations assigning characterizing flavour properties to these additives. The toxicological health risks of repeated capsaicinoid exposures due to ONP use, in combination with nicotine and other constituents, need to be assessed.

Tobacco use is the leading preventable cause of death worldwide. Anxiety increases the risk for smoking, and smoking in turn increases the risk for anxiety disorders. There is therefore a need to identify interventions that reduce anxiety, in general and in the context of smoking, without producing sedation. Kava (Piper methysticum), a natural product with a long history of indigenous use, has been shown to have anxiolytic and calming effects and reduce nicotine withdrawal. The current study examined whether kava without the hepatotoxic flavokavains A and B (AB-free) could reduce anxiety-like behavior in mice repeatedly treated with nicotine. Male and female C57BL/6NCrl mice received either a control diet or an AB-free kava-supplemented diet and underwent two blocks of nicotine treatments. Mice underwent a first block of five every-other-day injections of nicotine (0.5 mg/kg) or saline, with open field testing after each injection, followed one week later by a nicotine challenge. A second block of injections was given using the same injection schedule, followed by a second challenge one week later, and two weeks afterward mice received a final challenge in a novel open field. During the first treatment block, AB-free kava significantly increased center time overall, an effect most pronounced in saline-treated animals, and increased locomotor activity, while nicotine decreased both measures. During the second challenge, nicotine reduced center time but not locomotor activity, and AB-free kava increased center time in saline-treated animals only. During the final challenge, nicotine reduced both measures, whereas AB-free kava increased center time regardless of nicotine treatment, and kava-treated animals also showed a near-significant increase in center entries. These results suggest that AB-free kava reduces anxiety-like behavior without inducing sedation but does not prevent nicotine-induced suppression of exploratory behavior.

Cigarette smoking remains one of the most important preventable causes of premature death worldwide. However, the mechanisms sustaining nicotine dependence and relapse are incompletely understood, particularly the role of impulsive action in persistent tobacco use. Dopamine D1 and nicotinic acetylcholine receptors both regulate nicotine-related behavior, but whether they contribute differently to nicotine-motivated responding and nicotine-induced impulsive action is unclear. The present study examined the effects of D1 receptor blockade and stimulation in male and female rats trained to self-administer nicotine intravenously in a Go/No- Go task. Nicotine was available during Go periods but not during No-Go periods, and impulsive action was measured as the percentage of active lever responses during No-Go periods. The D1 receptor antagonist SCH23390 reduced nicotine intake and active lever responding during Go periods and affected the percentage of active lever responses during No-Go periods. However, SCH23390 also reduced inactive lever responding, so its effect on impulsive action could not be separated from a general reduction in operant output. In contrast, the D1 receptor agonist A77636 reduced nicotine intake and Go-period responding without affecting No-Go responding, indicating that D1 receptor stimulation reduced nicotine-motivated responding without altering impulsive action. Rats showed greater No-Go responding during nicotine self-administration than during saline self-administration, indicating that nicotine increased impulsive action rather than general operant responding. The non-selective nicotinic antagonist mecamylamine reduced nicotine-motivated responding and decreased No-Go responding, indicating reduced impulsive action. These findings suggest that nicotinic acetylcholine receptor signaling plays a major role in nicotine-induced impulsive action, whereas D1 receptor signaling contributes more clearly to nicotine-motivated responding. D1 receptor agonism may reduce nicotine-motivated behavior without affecting nicotine-induced impulsive action.

BackgroundAlthough nicotine reinforcement is often attributed to mesolimbic dopamine neurons in the ventral tegmental area, accumulating evidence indicates that additional brain circuits contribute to its reinforcing effects. AimsThe hypothalamic supramammillary region (SuM) has been implicated as one such substrate, yet the cellular targets and circuit mechanisms through which nicotine engages this region remain poorly understood. MethodsWe combined RNAscope in situ hybridization to identify nicotinic acetylcholine receptor (nAChR) subunits, intravenous nicotine self-administration in mice to determine doses that reliably support reinforcement, and fiber photometry to monitor calcium activity in SuM VGluT2 neurons in vivo. ResultsMice exhibited reliable nicotine self-administration across a range of doses under fixed-ratio and progressive-ratio schedules. RNAscope analysis revealed prominent expression of the {beta}2 nAChR subunit in VGluT2-expressing neurons projecting from the SuM to the medial septum. Fiber photometry recordings showed that reinforcing doses of nicotine produced rapid, infusion-locked increases in GCaMP signals in SuM VGluT2 neurons. ConclusionsThese findings identify nAChR-expressing SuM neurons as a candidate circuit substrate engaged by reinforcing doses of nicotine and extend current models of nicotine reinforcement beyond canonical mesolimbic dopamine pathways.

Introduction: Pediatric nicotine exposures remain an important and preventable public health issue, particularly with the rapid expansion of electronic nicotine delivery systems. This study compared demographic characteristics, exposure circumstances, and clinical outcomes between pediatric cases involving nicotine devices and bottled liquids reported to U.S. poison centers. Method: This retrospective cohort study analyzed National Poison Data System cases from 2011-2022 involving children aged less than 6 years exposed to nicotine devices or bottled liquids. Analyses were limited to cases with definitive medical outcomes. The primary outcome was defined as a moderate or major clinical effect or death. Odds ratios with 95% confidence intervals were calculated, with a secondary analysis restricted to route-concordant exposures. Results: The final cohort included 15,497 cases: 10,168 device exposures and 5,329 liquid exposures. Demographic characteristics were similar between groups. Device exposures more frequently involved inhalation, while ingestion predominated overall. Clinical effects were typically mild and transient, with vomiting and coughing most commonly reported. The primary outcome occurred in 1.9% of device cases and 2.0% of liquid cases (OR = 1.05; 95% CI 0.82-1.34). A secondary analysis restricted to inhalation-only device exposures and ingestion-only liquid exposures similarly found no significant difference in clinically important outcomes (OR = 1.38; 95% CI 0.92-2.12). Two deaths occurred, one in each group. Conclusion: These findings suggest that, despite differences in formulation and route of exposure, nicotine devices and bottled liquids produce broadly similar clinical toxicity profiles in young children. Prevention strategies should address all household nicotine products rather than focusing on specific delivery systems.

Background: The nicotine analog 6-methyl nicotine (6-MN) has appeared in commercial e-cigarette liquids, and other products, spurring interest in determining the extent to which it conveys similar effects to those of nicotine. Objective: To determine if 6-MN acts like nicotine to decrease body temperature, decrease nociception, suppress wheel activity and reinforce operant behavior when delivered by vapor inhalation using an Electronic Nicotine Delivery System (ENDS; "e-cigarette") approach in a rat model. Methods: Male and female (N=8 per sex) young adult Sprague-Dawley rats were evaluated for rectal temperature and nociceptive responses (warm water tail-withdrawal) to the inhalation of vapor from (-)-6-MN or (-)-nicotine in concentrations ranging from 5-30 mg/mL in the propylene glycol vehicle. Rats were then assessed for the reinforcing effects of nicotine and 6-MN using a vapor self-administration procedure and the rate suppressing effects of nicotine and 6-MN on wheel activity following injection. Results: Inhalation of nicotine or 6-MN for 30 minutes decreased the rectal temperature and increased tail-withdrawal latency of female and male rats in a concentration-dependent manner. The magnitude of the effects of 6-MN and nicotine were similar at similar vapor concentrations. Operant responding for 6-MN vapor was increased by pre-treatment with the antagonist mecamylamine. 6-MN was more potent than nicotine at suppressing wheel activity after injection. Conclusions: 6-MN induces effects very similar to those of nicotine, at a similar potency when inhaled and at a slightly increased potency when injected.