Nicotine and Tobacco Research

BackgroundOral nicotine pouches (ONPs) have become the second most commonly used nicotine product among U.S. youth. However, little is known about how ONP use is distributed across population subgroups and how strongly it is patterned by use of other tobacco or nicotine products. MethodData were drawn from the 2021-2023 waves of the National Youth Tobacco Survey (NYTS), a nationally representative survey of U.S. middle and high school students (N = 66,349). We estimated the annual survey-weighted prevalence of current ONP use ([≥]1 day in the past 30). Using 2023 data (N = 20,174), we estimated prevalence by demographics and other tobacco/nicotine product use, and fitted survey-weighted Poisson regression models to estimate associations of current ONP use with demographics and other nicotine/tobacco product use. ResultsIn 2023, 1.6% reported current ONP use (95% confidence interval [CI] 1.0-2.1), up from 0.8% in 2021 (95% CI 0.5-1.0). Prevalence in 2023 was higher among males (2.3%, 95% CI 1.5-3.1) than females (0.8%, 95% CI 0.4-1.3), and among students who used any other tobacco or nicotine product (13.4%, 95% CI 10.3-16.5) than those who did not (0.4%, 95% CI 0.1-0.8). In fully adjusted models, use of nicotine products other than cigarettes or e-cigarettes showed the strongest association with ONP use (APR 21.1, 95% CI 13.0-34.0), followed by cigarette smoking (APR 2.0, 95% CI 1.1-3.7) and e-cigarette use (APR 1.9, 95% CI 0.8-4.5). Most current ONP users also used other tobacco/nicotine products (75.0%), though 16.6% reported no lifetime use of other products. ConclusionsOverall ONP prevalence among U.S. youth remains low but is increasing. While ONP use is largely concentrated in youth who use other nicotine/tobacco products, it is also increasing among adolescents who are otherwise nicotine-naive. These findings highlight the need for continued monitoring and targeted regulations that balance harm reduction for people who smoke against the risk of expanding nicotine dependence among youth. Key Points QuestionWhat are the prevalence, demographic patterns, and tobacco/nicotine co-use profiles of oral nicotine pouch users among US middle and high school students? FindingsIn this cross-sectional study of 66,349 students from the 2021-2023 National Youth Tobacco Survey, current oral nicotine pouch use doubled from 0.8% in 2021 to 1.6% in 2023. Most users also used other tobacco or nicotine products, but the proportion of current users with no lifetime use of other products increased from 7.4% to 16.6%. MeaningAlthough oral nicotine pouch use among US youth remains low, increasing uptake among adolescents without prior tobacco or nicotine exposure suggests a need for targeted prevention efforts alongside continued surveillance.

Abstract Importance: The overall prevalence of youth nicotine and tobacco product use has declined over recent years, but the product landscape continues to evolve rapidly, particularly with new disposable e-cigarettes and oral nicotine pouches. Objective: To examine changes between 2024 and 2025 in the prevalence of nicotine and tobacco product use among US middle and high school students and describe shifts in product characteristics among current e-cigarette and nicotine pouch users. Design, Setting, and Participants: Repeated cross-sectional study using nationally representative data from the 2024 and 2025 National Youth Tobacco Survey (NYTS), a school-based survey of US students in grades 6-12 (approximately ages 11-18). The analytic sample included 29,678 students in 2024 and 23,557 students in 2025. Exposures: Survey year (2025 vs 2024). Main Outcomes and Measures: Past 30-day use of nicotine/tobacco products, including e-cigarettes, nicotine pouches, cigarettes, and other combustible and non-combustible products. Among current e-cigarette and nicotine pouch users, frequency of use, device type, brands, and flavors were assessed. Results: In 2025, 7.2% (95% CI, 6.4-8.2%) of US middle and high school students reported past 30-day use of any nicotine/tobacco product, compared with 8.1% (7.4-8.9%) in 2024. E-cigarettes remained the most commonly used product (5.2%, 4.5-5.9%); 1.7% (1.4-2.1%) used nicotine pouches, 1.7% (1.4-1.9%) smoked cigarettes, and 2.7% (2.4-3.1%) smoked any combustible tobacco product. Among current e-cigarette users, 40.7% (36.7-44.9%) reported frequent use and 27.0% (24.0-30.2%) reported daily use in 2025. Disposable e-cigarette use increased from 55.8% (52.6-59.0%) in 2024 to 66.7% (62.5-70.7%) in 2025, while pod/cartridge device use declined. Flavored product use was reported by 90.0% of e-cigarette users and 88.0% of nicotine pouch users. The most commonly reported brands were Geek Bar among e-cigarette users (61.1%) and ZYN among nicotine pouch users (69.4%). Conclusions and Relevance: Overall youth nicotine and tobacco use remains relatively low, but the product landscape is evolving rapidly, with increasing disposable device use and shifting brand preferences. These findings highlight the importance of ongoing, product-specific surveillance to inform public health strategies and regulatory policies.

BackgroundDespite their potential to serve as a reduced-harm alternative to combustible tobacco, e-cigarette take-up remains low among older (45+) adult smokers, especially in the U.S. While social media is a known driver of vaping attitudes and behaviors in younger populations, its influence on older smokers is poorly understood. This paper provides the first focused analysis of e-cigarette-related social media exposure in this population, documenting its prevalence, characteristics, and attitudinal correlates. MethodsData come from an opt-in survey of U.S. adults (N = 974) recruited via Prolific, comprising three groups: (i) non-vaping smokers aged 45+ (N = 484), (ii) former-smoking vapers aged 45+ (N = 149), and (iii) any-vaping-status smokers aged 18-35 (N = 341). Descriptive statistics, weighted to U.S. population benchmarks, characterize self-reported exposure to e-cigarette-related content on social media. Logistic regressions estimate associations between exposure and intentions for future e-cigarette use, e-cigarette harm perceptions, and related attitudes. ResultsOlder smokers (35.3%) reported exposure to e-cigarette-related content on social media less frequently than both older vapers (44.0%) and younger smokers (72.0%). For older smokers, e-cigarette health risks were the most frequently reported topic of content viewed, followed by youth vaping and e-cigarette addiction. Among this group, exposure was positively associated with stated intentions for future e-cigarette use. Exposure was not significantly associated with perceived e-cigarette harms for any group. ConclusionsFindings provide suggestive evidence that social media exposure may promote e-cigarette adoption among older smokers. However, the cross-sectional design limits causal inference, and the observed associations may reflect selection bias or reverse causality. If a causal relationship exists, the patterns observed suggest that exposure influences e-cigarette adoption through mechanisms other than updating beliefs about e-cigarette risks. While these results tentatively support the potential of social media as a channel for older-smoker harm reduction, any policy applications must carefully weigh privacy concerns and risks to youth. Rigorous experimental studies are needed to confirm these findings and clarify how social media might be leveraged to improve public health outcomes among older smokers.

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.

Importance: Understanding patterns of substance use and environmental exposures to tobacco, cannabis, and electronic nicotine delivery systems (ENDS) among youth is critical for developing targeted prevention strategies, particularly as co-use of tobacco, ENDS, and cannabis becomes more prevalent. Objective: To identify latent classes of tobacco, ENDS, and cannabis use, and environmental exposures to these products among adolescents and emerging adults. Design, Setting, and Participants: Data from the Environmental influences on Child Health Outcomes (ECHO) consortium (3rd data release, 2018 to 2022) were analyzed from March 2025 to January 2026. The sample (N=2,786) included early adolescents (ages 11 to 13; n=226, 7.9%), middle adolescents (ages 14 to 17; n=1,248, 43.4%), and late adolescents/emerging adults (ages 18 to 24; n=1,402, 48.7%) from 19 ECHO cohorts. Main Outcomes and Measures: The Youth Risk Behavior Survey, Substance Use module measured experimental and current use of cannabis, ENDS, and tobacco products, as well as daily environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke within home and social contexts. A multiple group latent class analysis was used to identify distinct latent classes of substance use and environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke and compared class prevalences across early, middle, and late adolescence. Results: Four latent classes were identified, including: No Use/No Exposure (53%), No Use, Polyexposure (10%), Experimental Use/Low Exposure (22%), and Polysubstance Use/High Polyexposure (14%). Cannabis was the most used substance (34% experimental or current use) and the most common source of environmental exposure (20%), followed by ENDS use (26% experimental or current use; 19% environmental exposure) and combustible tobacco (15% use; 19% environmental exposure). The No Use/No Exposure and No Use/Polyexposure classes were primarily made up of early and middle-aged adolescents, whereas the Experimental Use/Low Exposure and Polysubstance Use/High Polyexposure classes primarily consisted of late adolescents and emerging adults. Conclusions: Our study revealed distinct, developmentally patterned groupings of substance use and environmental exposure among US adolescents and emerging adults, highlighting the need for developmentally tailored interventions, messaging, and policies that address both active use and environmental exposure across adolescence.

"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.

BackgroundAs cigarette smoking continues declining among youth and young adults, smoking rates among older Americans remain unchanged. Historically, cigarette and, more recently, e-cigarette tax policies influenced smoking behavior in younger smokers. Understanding how older smokers respond to tax changes can inform public health strategies. MethodsWe assembled a quarterly panel of state cigarette and e-cigarette tax rates using the CDC STATE System Tobacco (2000-2024) and E-Cigarette Legislation databases (2015-2024), then merged these data to individual-level survey responses from the Behavioral Risk Factor Surveillance System (BRFSS). Our sample included all adults aged [≥]65, but our main specification included adults with a history of smoking. We estimated two-way fixed-effects population-weighted linear probability regression models of current smoking and past-year quit attempts. ResultsAmong 3,117,382 adults, 50% had a history of smoking; from which 18% currently smoked. A one-dollar tax increase was associated with current smoking: cigarette tax = -0.61-percentage points (CI = -0.94,-0.28); e-cigarette tax = +0.19-percentage-points (CI = 0.14,0.24). There was no association between cigarette taxes and quit attempts. A one-dollar increase in e-cigarette tax was associated with reduced quit attempts (-0.17-percentage-points; CI = -28,-0.06). Approaching tax parity by one dollar was associated with increased current smoking by 0.23-percentage-points (CI = 0.16,0.29) and reduced quit attempts by -0.17-percentage-points (CI = -0.29,0.05). ConclusionsOlder American smokers appear responsive to cigarette and e-cig tax changes. Policies increasing the relative cost of e-cigarettes may impede cessation and perpetuate smoking rates in older generations at the highest risk of smoking related harm. ImplicationsMany studies have investigated the impact of cigarette and e-cigarette tax changes on smoking behavior in youth or younger adults. This study adds new evidence quantifying how new cigarette and e-cigarette taxes change smoking behavior among older adults, a population yet to realize reductions in smoking despite higher risk of tobacco related harm. Analyzing large, population-based survey data, we show that older smokers change smoking behavior due to cigarette and e-cigarette taxes. Taxation of e-cig products may produce unintended harm among older smokers. Specifically, approaching tax parity may increase cigarette smoking and reduce quit attempts among older adults with a history of smoking.

IntroductionAlthough prior studies suggest e-cigarette use is associated with worse mental health, it remains unclear whether these associations persist independent of diagnosed depression and how tobacco use and depression jointly affect health-related quality of life. Although the long-term health risks of vaping are still unknown, self-reported health is a reliable measure of quality of life. This study provides the first health utility estimates of the independent and combined effects of cigarette use, e-cigarette use, and depression on health-related quality of life. MethodsWe analyzed 2022-2023 Behavioral Risk Factor Surveillance System data on health-related quality of life as measured by self-reported physically or mentally unhealthy days in the past 30 days. The average number of unhealthy days was estimated by age, gender, smoking status (current versus non-smoking), depression status (received a prior diagnosis), and current e-cigarette use status (every day or some day use). We converted the number of overall healthy days into EQ-5D utility scores by age-specific percentile matching of BRFSS and MEPS distributions, a method developed by Jia and Lubetkin. ResultsCigarette use, e-cigarette use, and depression were each associated with worse health-related quality of life. Mentally unhealthy days increased with the accumulation of these conditions. Associations with physically unhealthy days followed a similar pattern, particularly among younger adults, although the magnitude of association was smaller. E-cigarette use alone was associated with 2.0-4.2 (95% CI: 2.0-4.6) additional mentally unhealthy days per month across all age groups. Notably, e-cigarette use was independently associated with poorer mental health among adults aged 18-64 with or without diagnosed depression. After accounting for smoking and depression status, e-cigarette use was associated with disutility scores of 0.011 in men and 0.015 in women among young adults, with the largest losses observed when multiple conditions co-occurred. ConclusionE-cigarette use is associated with poorer health-related quality of life, particularly among younger adults, and these effects are amplified when combined with cigarette use and depression. Quantifying these joint impacts as health utility losses highlights the importance of addressing e-cigarette use within integrated tobacco control and mental health policies, especially for young populations.

BackgroundTobacco use among young people remains a major public health concern in Indonesia, where smoking prevalence is high and metabolic risk factors such as overweight and hypertension are increasing. Evidence linking smoking behavior, particularly e-cigarette use, to early cardiometabolic risk in low- and middle-income countries is still limited. This study examined overweight and hypertension profiles among young smokers using nationally representative data from Indonesia. MethodsThis secondary analysis used data from the Indonesian Health Survey 2023. Participants were young adults aged 18-25 years with complete information on smoking status, anthropometry, and blood pressure (n = 12,770). Smoking status was categorized as conventional smokers, e-smokers, and dual smokers. Outcomes included overweight/obesity (BMI [≥]23 kg/m2), central obesity (waist circumference [≥]90 cm for men and [≥]80 cm for women), and hypertension ([≥]130/80 mmHg). Logistic regression models estimated adjusted odds ratios (AOR) controlling for age, gender, smoking duration, residence, and socioeconomic proxy variables. ResultsMost respondents were conventional smokers (94%), followed by dual smokers (4%) and e-smokers (2%). E-smokers showed higher mean BMI and the greatest prevalence of overweight/obesity (40%) and central obesity (18%). After adjustment, e-smokers and dual smokers had higher odds of overweight/obesity (AOR = 1.37 and 1.41, respectively) and central obesity (AOR = 1.47 and 1.53, respectively) compared with conventional smokers. Hypertension prevalence (11-13%) did not differ significantly across smoking categories. ConclusionAmong young Indonesian smokers, e-cigarette and dual use were associated with higher odds of overweight and central obesity but not hypertension. These findings highlight the importance of integrating tobacco control with early metabolic risk prevention strategies targeting youth.

Tobacco use disorder is a chronic condition characterized by compulsive nicotine use, withdrawal, and relapse following abstinence. Impulsivity contributes to persistent nicotine use and poor cessation outcomes. This study examined whether nicotinic acetylcholine receptor (nAChR) modulators alter impulsive action in a nicotine self-administration Go/No-Go task in male and female rats. Rats acquired intravenous nicotine self-administration and were then trained in a Go/No-Go procedure in which active lever presses were reinforced during Go periods but not during No-Go periods. We then assessed the effects of varenicline (0.1-3 mg/kg), nicotine (0.1-0.6 mg/kg), and the nAChR antagonist mecamylamine (0.5-2 mg/kg) in the Go/No-Go procedure. Varenicline and nicotine pretreatment reduced active responding during both Go and No-Go periods, whereas mecamylamine selectively reduced responding during No-Go periods. Mecamylamine decreased the percentage of active responses during No-Go trials, indicating reduced bias toward the nicotine-associated lever. In contrast, nicotine and varenicline did not alter response allocation, suggesting that their effects reflected nonspecific reductions in responding rather than changes in impulsive action. No sex differences were observed. Substituting saline for nicotine during self-administration did not alter active responding during Go periods, but rats in the saline group had fewer active responses during No-Go periods than rats in the nicotine group. These results show that chronic nicotine self-administration increases impulsive action and that nAChR antagonism, but not agonism or partial agonism, reduces nicotine-related impulsive action. This work supports the utility of the Go/No-Go self-administration task for investigating nAChR-dependent mechanisms underlying nicotine-induced impulsivity.

ImportanceChronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality in the United States (US), largely driven by cigarette smoking and characterized by progressive lung injury. While e-cigarettes are promoted as a less harmful alternative to cigarette smoking, their long-term health effects, including the impact of prolonged use on COPD incidence among adults who have smoked, are not well understood. ObjectiveTo evaluate the prospective association between duration of e-cigarette use and incident COPD among US adults aged 40 years or older with a history of cigarette smoking, and to determine whether baseline respiratory symptoms modify this association. Design, Settings, and ParticipantsWe used data from Waves 4 to 7 (2017-2022) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative US longitudinal cohort study. Our analysis included adults aged 40 years or older who currently or formerly smoked cigarettes. Main Outcomes and MeasuresThe outcome was incident, self-reported COPD diagnosis. The main exposure was the time-varying duration of e-cigarette use. Baseline functionally important respiratory symptoms were defined by a validated index. Multivariable models adjusted for demographics, COPD risk factors, and detailed tobacco use history, including cigarette smoking status, time since quitting, and pack-years. ResultsAmong 4,895 adults aged 40 year or older who currently or formerly smoked cigarettes, 408 reported an incident COPD diagnosis. Among individuals with baseline respiratory symptoms, longer e-cigarette use duration was associated with increased COPD risk (adjusted hazard ratio [AHR]: 1.28, 95% CI: 1.16, 1.40), whereas no significant association was observed among those without baseline respiratory symptoms (AHR: 1.01, 95% CI: 0.92, 1.12). Results were consistent after adjusting for cumulative cigarette exposure and other risk factors and remained robust across multiple sensitivity analyses. Conclusion and RelevanceProlonged e-cigarette use may increase COPD risk among individuals with pre-existing respiratory vulnerabilities. Although switching from combustible cigarettes remains an important harm reduction strategy, behavioral counseling and pharmacotherapy should be prioritized for those at high risk for COPD, with e-cigarette cessation support available to high-risk former smokers. Continued surveillance and research are warranted as e-cigarette products and use patterns evolve. Key PointsO_ST_ABSQuestionC_ST_ABSDoes longer e-cigarette use increase COPD risk in adults with a smoking history? FindingsIn this national cohort study of U.S. adults aged 40+ who currently or formerly smoked, e-cigarette duration was associated with higher self-reported COPD incidence among individuals with respiratory symptoms at baseline (adjusted hazard ratio [AHR] 1.28, 95% CI 1.16, 1.40) but not among those without symptoms (AHR 1.01, 95% CI 0.92, 1.12). MeaningProlonged e-cigarette use may increase COPD risk among individuals with respiratory vulnerabilities. While cigarette cessation should remain the priority, evidence-based e-cigarette cessation strategies are needed to prevent long-term use in this population.

ObjectiveTo evaluate the effectiveness of various Large Language Models (LLMs) in identifying reliable predictors of Electronic Nicotine Delivery Systems (ENDS) initiation among adolescents, using solely large-scale survey variable descriptions. MethodsA cohort of 7,943 tobacco-naive adolescents aged 12-16 years from the Population Assessment of Tobacco and Health (PATH) Study was analyzed to predict ENDS use at wave 5. Four instruction-tuned LLMs - GPT-4o, LLaMA 3.1-70B, Qwen 2.5-72B-Instruct, and DeepSeek-V3 - were systematically evaluated for text-based feature selection using only variable descriptions from wave 4.5. Selected features were used to train LightGBM classifiers, with model performance compared to a baseline. ResultsOur findings reveal notable consistency among the four instruction-tuned LLMs, with substantial overlap in the top predictors each model identified. These selected variables spanned critical domains such as peer and household influence, risk perception, and exposure to tobacco-related cues. LightGBM classifiers trained on PATH wave 4.5-5 data using features selected by the LLMs demonstrated strong predictive performance. Notably, Qwen 2.5-72B-Instruct achieved an AUC of 0.791 with 30 predictors, surpassing the baseline AUC of 0.768. DiscussionThe substantial overlap among the top predictors identified by different LLMs suggests a shared reasoning process, despite variations in model architecture and training. LightGBM classifiers trained on these LLM-selected features achieved performance comparable to, or exceeding, models trained on the full set of survey variables, underscoring the high quality of features selected solely from textual descriptions. Moreover, these findings are consistent with previous tobacco regulatory research, further validating the effectiveness of LLM-driven feature selection. ConclusionInstruction-tuned large language models can effectively perform text-based feature selection using survey variable descriptions alone, without accessing raw survey data. This scalable, interpretable, and privacy-preserving framework holds promise for behavioral health research and tobacco use surveillance.

BackgroundInhaled combusted cannabis and co-use of combusted cannabis and nicotine electronic cigarettes (nECIGs) are on the rise, yet their long-term cardiovascular risk is unclear due to the high prevalence of confounders in observational human studies. Using primary plasma and monocytes and a novel ex vivo mechanistic model of two early steps in atherogenesis, this study examined whether chronic combusted cannabis use is associated with atherogenic changes, as estimated by 1) monocyte transendothelial migration (MTEM), and 2) monocyte-derived foam cell formation (MDFCF), and whether nECIG co-use further amplifies this risk. MethodsA cross-sectional parallel group comparison study was conducted in healthy adults (21-30 years) who chronically 1) used combusted cannabis, 2) co-used both combusted cannabis and nECIGs, and 3) were non-using controls. Using our ex vivo atherogenesis assay, primary outcomes of MTEM, MDFCF, and median fluorescence intensity (MFI) of the lipid-staining fluorochrome BODIPY were determined using primary plasma and autologous primary monocytes from participants. Using flow cytometry and the fluorochrome CELLROX, cellular oxidative stress (COS) in monocytes was determined. ResultsOf the 134 participants, 59 used cannabis, 26 co-used cannabis/nECIG, and 49 were non-using controls. The groups had similar age, sex, and race. Median MTEM was 1.13 fold greater in people who used cannabis compared to non-users 27.8% (IQR 26.1:29.2%) vs 24.5%, (IQR 22.9:27.4%), p<0.0001, and tended to be greater in people who co-used cannabis/nECIG by 1.22-fold 34.1%, (IQR 29.9:38.3%, p=0.17). Median MDFCF and MFI were also increased in people who used cannabis compared to non-users (MDFCF 36.3%, IQR 31.8:35.8%, vs 26.6%, IQR 23.8:25.8%, 1.36-fold and MFI 1163.8, IQR 1042.8:1155.0, vs 940.2 IQR 849.9:1101.4, 1.24-fold) and were further increased in people who co-used cannabis/nECIG (MDFCF 48.7%, IQR 37.3:52.4%, 1.34-fold, MFI 1433.7, IQR 1263.8:1686.4, 1.23-fold; all comparisons p<0.008). Foam cell formation, but not transendothelial migration, was strongly positively correlated with COS. All primary outcomes increased with greater frequency of cannabis and/or nECIG use. ConclusionsIn healthy young adults, exclusive cannabis use is associated with increased atherogenic properties of monocytes and plasma, and this atherogenic effect is further amplified by co-use of nECIGs.

BackgroundChronic pain is one of the most common reasons for medicinal cannabis use, yet the neural mechanisms underlying cannabis-related modulation of pain remain poorly understood. Both pain and cannabis use independently alter functional connectivity within the brains default mode network (DMN) that modulate interoception and self-referential aspects of pain processing. The goal of this study was to examine the interaction between pain and cannabis use on DMN connectivity. MethodsWe measured DMN resting state fMRI functional connectivity (rsFC), past year pain frequency, and cannabis use measures (i.e., grams per day, days a week, years of regular use) from 119 adults who use cannabis near-daily (68 men; Mage= 22.66, SE= .31). Generalized linear models were used to test the main effects and interactions of pain frequency and cannabis use variables. ResultsResults indicated significant interactions between pain and cannabis use where more frequent pain was (1) negatively associated with weekly use or years of use in l-IPL-PCC and r-IPL-PCC rsFC, (2) whereas it was positively associated with daily grams of cannabis in l-IPL-r-IPL rsFC and r-IPL-PCC rsFC (BH-FDR-corrected p< .05). ConclusionsFirst, these findings demonstrate that pain frequency is a key context shaping the neurobiological correlates of exposure to cannabis. Second, divergent interaction effects suggest that, in the context of more frequent pain, cannabis use may relate to rsFC through distinct neural processes that depend on cumulative vs. proximal effects.

Tobacco use disorder (TUD) remains a leading cause of preventable mortality, and existing pharmacotherapies yield 12-month abstinence rates below 30%. As cannabis legalization expands, approximately 18-22% of people who use tobacco report concurrent cannabis use, yet the impact of co-use on cessation outcomes and the therapeutic potential of endocannabinoid system (ECS) modulation remain unclear. We conducted a translational systematic review and meta-analysis following PRISMA 2020 guidelines, searching Ovid MEDLINE, Embase, APA PsycInfo, and Web of Science through January 2026 (PROSPERO: CRD420250652724). Three study categories were eligible: observational studies of cannabis co-use and cessation outcomes; preclinical studies of cannabinoid modulators on nicotine-related behaviors; and human experimental studies of ECS-targeted interventions. Of 4,869 records screened, 52 studies met inclusion criteria. Meta-analysis of 18 observational studies (N=229,630) revealed that cannabis use was associated with 35% lower odds of achieving tobacco smoking cessation (OR=0.65; 95% CI: 0.55-0.78; p<0.0001; I{superscript 2}=88.1%). Preclinical evidence (15 studies) demonstrated that CB1 receptor antagonists robustly reduced nicotine self-administration and reinstatement, while cannabidiol (CBD) attenuated both nicotine intake and withdrawal without affecting food reinforcement. Clinical translation of CB1 receptor inverse agonists failed due to psychiatric adverse effects, but CBD showed promise by reducing cigarette consumption by 40%, reversing attentional bias to smoking cues, and alleviating withdrawal severity. These findings distinguish naturalistic cannabis exposure from potentially beneficial targeted ECS modulation, and support CBD as a promising candidate for adequately powered tobacco cessation trials.

Alcohol Use Disorder (AUD) is a multifactorial condition with severe individual and societal impacts. Extending our 2024 study, this work examines lifestyle, background, and family history determinants of AUD using an expanded dataset from the All of Us Research Program. The updated analysis includes approximately 2.5 times more participants than the prior study, enabling improved statistical power and evaluation of result stability over time. Using interpretable machine learning models and statistical analyses, we identified annual income, residential stability, recreational drug use, sex/gender, marital status, education, and family history as key contributors to AUD risk. Annual income remained the most influential predictor across both datasets, while other feature rankings showed modest shifts. Family history factors continued to demonstrate non-linear effects, with close relatives AUD status remaining influential despite differences between statistical association and predictive importance. In predicting AUD versus non-AUD status, Random forest models achieved the highest classification accuracy (81%), consistent with 2024 results but with improved precision for identifying AUD cases. Overall, the findings confirm the robustness of previously identified AUD determinants and underscore the need for coordinated, multi-level prevention strategies addressing behavioral, familial, and structural factors contributing to AUD.

Despite high risk, exposure to indoor second-hand smoke (SHS) among the non-smokers is scarcely studied in India. To address this gap, we assessed the prevalence and predictors of indoor SHS among the non-smoker household population of India. Bivariate and multivariate analysis of Demographic and Health Survey 2021 data of 1,529,486 household members was carried out. For India, the prevalence of indoor SHS exposure was 40.6 percent. Adults (aOR 0.88; 95% CI 0.87-0.89), educated individuals (aOR 0.87; 95% CI 0.86-0.88), married couples (aOR 0.72; 95% CI 0.71-0.73), and occupants of pucca houses (aOR 0.77; 95% CI 0.75-0.78) had lower odds of indoor SHS exposure than their respective reference categories. Females (aOR 1.54; 95% CI 1.53-1.56), higher household size (aOR 1.07; 95% CI 1.07-1.08), joint family (aOR 1.11; 95% CI 1.10-1.12), Muslims (aOR 1.18; 95% CI 1.17-1.20), Scheduled Tribes (aOR 1.15; 95% CI 1.14-1.17), rural residents (aOR 1.26; 95% CI 1.25-1.27), and the northeastern zone (aOR 1.12; 95% CI 1.10-1.14) were positively associated with indoor SHS exposure. Every four out of ten Indians experienced indoor SHS exposure. Half of them were daily exposed to indoor SHS. Particularly children, women, and occupants of Kachha houses were at higher risk. The susceptibility among these high-risk groups to cancers, respiratory diseases, and cardiovascular diseases can be averted by improving housing, increasing access to tobacco cessation services and additional pharmacotherapies, and strict enforcement of tobacco control regulations in India.

ABSTRACT Background and aims: Mental and behavioral disorders due to use of tobacco (MBDT) present a critical challenge to global health, yet modifiable lifestyle factors for reducing its risk remain poorly understood. Given that dietary fibre can affect mental health through gut-brain communication, we sought to explore how fibre intake relates to MBDT risks in smokers. Methods: We specifically evaluated the link between dietary fibre intake and MBDT within a smoking population. Utilizing the UK Biobank (UKB) database, we performed cross-sectional (N=19,943) and prospective cohort (N=19,885) evaluations applying logistic and Cox proportional hazards models, respectively. To determine potential causality, two-sample Mendelian randomization (MR) was applied, relying on GWAS summary data derived from the IEU Open GWAS Project and FinnGen repositories. Results: Cross-sectional findings indicated that individuals in the top quartile (Q4) of fibre intake exhibited decreased MBDT risks relative to the bottom quartile (Q1) (OR: 0.32, 95% CI: 0.13-0.79). Over a median observation time of 12.84 years, the prospective evaluation demonstrated a notable inverse correlation (Q4 HR: 0.46, 95% CI: 0.40-0.54). Non-linear modeling via restricted cubic splines uncovered an L-shaped dose-response curve. Furthermore, MR results confirmed a genetically predicted protective causality (IVW OR: 0.68, 95% CI: 0.49-0.95), which remained consistent across sensitivity validations. Conclusions: Among smokers, higher dietary fibre intake is robustly associated with a reduced risk of mental and behavioral disorders due to the use of tobacco, offering a modifiable dietary target for public health interventions.

IntroductionTobacco smoking is especially high among males in the Kingdom of Saudi Arabia (KSA). In 2019, 27.5% of males ages 15+ reported smoking. Despite a minimum age requirement of 18 years, data indicate that 6.8% of youth ages 13-15 currently smoke tobacco products. To reduce youth smoking, countries have raised the minimum purchase age to 21, also referred to as Tobacco 21. Except for Kuwait, no other Middle Eastern country has done so. We develop a tobacco smoking simulation model to project the potential impact of a national Tobacco 21 policy in Saudi Arabia. MethodsWe used data from three nationally representative health surveys in Saudi Arabia to develop the KSA Tobacco Control Policy (TCP) model, estimating smoking initiation and cessation rates for males, as smoking rates are low among females. A national Tobacco 21 policy was operationalized as a 34% (15%-53%) reduction to smoking initiation for ages 18-20. Economic impact was evaluated using the 2024 KSA value of a statistical life which ranges from $1.65 million to $5.15 million USD. ResultsUnder a status quo scenario, tobacco smoking prevalence in males would decrease to 10.2% by 2100. Implementation of Tobacco 21 in 2026 would decrease smoking prevalence to 9.4% (8.9%, 9.8%) by 2100. While modest, these reductions would eventually translate into nearly 5000 (2200, 7800) premature deaths averted with up to 155000 (69000, 241000) life years gained from 2026-2100, respectively. The total expected economic benefit ranges from $1.67 to $5.19 billion USD, equivalent to 6.25 to 19.45 billion SAR. DiscussionTimely implementation would support the KSA in its goals to reduce non-communicable disease and death; however, even under best-case conditions, a Tobacco 21 alone would not achieve the Vision 2030 smoking prevalence target of 9%. Additional policies that substantially increase smoking cessation are needed. What is already known on this topicThe leading causes of death in Saudi Arabia are all linked to tobacco smoking. Tobacco 21 policies have been pursued by numerous governments to reduce youth smoking, but such policies are lacking in Middle Eastern nations. What this study addsA nationwide Tobacco 21 policy in Saudi Arabia would reduce smoking initiation, smoking prevalence, and smoking-related mortality. Overall smoking prevalence among males ages 15+ would decline, and nearly 5000 premature deaths would be averted with up to 155,000 life years gained from 2026-2100, valued at 6.25 to 19.45 billion SAR. How this study might affect research, practice or policyThis study quantified for the first time the potential long-term benefits of a Tobacco 21 policy in Saudi Arabia for the male population. A Tobacco 21 policy would benefit future generations of young people by reducing their risk for heart disease, stroke, and cancer, currently the leading causes of death in the nation. However, additional efforts are needed in addition to Tobacco 21 policies to achieve tobacco smoking reduction goals.

Introduction: Monitoring 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. Methods: Using 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. Results. The 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. Conclusion. ENDS-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.