المؤلفون: Giberson, Jeremy, Nardone, Natalie, Addo, Newton, Khan, Sameera, Jacob, Peyton, Benowitz, Neal, St.Helen, Gideon

المصدر: Nicotine & Tobacco Research. 25(8)

مصطلحات موضوعية: Epidemiology, Public Health, Health Sciences, Tobacco Smoke and Health, Substance Misuse, Clinical Research, Brain Disorders, Prevention, Tobacco, Drug Abuse (NIDA only), Good Health and Well Being, Adult, Humans, Male, Female, Nicotine, Electronic Nicotine Delivery Systems, Tobacco Products, Cigarette Smoking, Surveys and Questionnaires, Vaping, Clinical Sciences, Public Health and Health Services, Marketing, Public health

الوصف: IntroductionThis study examined user behavior, e-cigarette dependence, and device characteristics on nicotine intake among users of pod-mod e-cigarettes.Aims and methodsIn 2019-2020, people who use pod-mods in the San Francisco Bay Area completed questionnaires and provided a urine sample for analysis of total nicotine equivalents (TNE). The relationship between TNE and e-cigarette use, e-cigarette brands, e-liquid nicotine strength, e-cigarette dependence, and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), as a measure of combustible cigarette exposure, were examined.ResultsOf 100 participants (64% male, 71% in the 18-34 age group, 45% white), 53 used JUUL primarily, 12 used Puff Bar primarily, and 35 used other brands, including Suorin; 48 participants reported current cigarette smoking. Participants most often reported use of e-liquid with 4.5%-6.0% nicotine (68%), fruit (35%), tobacco (28%), and menthol or mint flavors (26%), used e-cigarettes on 25.5 (SD = 6.3) days a month, 10.2 (SD = 14.2) times a day, and 40% used 1-2 pods/cartridges per week. In bivariate analysis, urinary TNE was higher with greater frequency (days used) and intensity (number of pods used) of e-cigarette use, e-cigarette dependence, and combustible cigarette use. In multivariable analysis, days of e-cigarette use in the last 30 days, number of pods used per week, and NNAL levels were significantly associated with TNE. There was no significant impact of e-liquid nicotine strength on TNE.ConclusionsNicotine intake among people who used pod-mod e-cigarettes increased with e-cigarette consumption and e-cigarette dependence, but not with e-liquid nicotine strength. Our findings may inform whether FDA adopts a nicotine standard for e-cigarettes.ImplicationsThe study examined how device and user characteristics influence nicotine intake among pod-mod e-cigarette users. Nicotine intake increased with frequency (days of e-cigarette use in past 30 days) intensity of use (number of pods used per day) and e-cigarette dependence but not with the flavor or nicotine concentration of the e-liquids. Regulation of nicotine concentration of e-liquids is unlikely to influence nicotine exposure among adult experienced pod-mod users.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7gm5809bTest

المؤلفون: Leavens, Eleanor L.S., Lambart, Leah M., St.Helen, Gideon, Benowitz, Neal L., Mayo, Matthew S., Farhad Mahmud, Kazi M., Arnold, Michael J., Nollen, Nicole L.

المساهمون: National Center for Advancing Translational Sciences, NHLBI, National Institute on Drug Abuse, National Cancer Institute, NIMHD

المصدر: Addictive Behaviors ; volume 155, page 108038 ; ISSN 0306-4603

مصطلحات موضوعية: Psychiatry and Mental health, Toxicology, Clinical Psychology, Medicine (miscellaneous)

الإتاحة: https://doi.org/10.1016/j.addbeh.2024.108038Test
https://api.elsevier.com/content/article/PII:S030646032400087X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S030646032400087X?httpAccept=text/plainTest

المؤلفون: Benowitz, Neal L, St.Helen, Gideon, Liakoni, Evangelia

المصدر: The Journal of Clinical Pharmacology. 61(S2)

مصطلحات موضوعية: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Substance Misuse, Drug Abuse (NIDA only), Cancer, Prevention, Tobacco, Tobacco Smoke and Health, Respiratory, Cardiovascular, Good Health and Well Being, Area Under Curve, Brain, Electronic Nicotine Delivery Systems, Humans, Metabolic Clearance Rate, Nicotine, Prevalence, Smoking Cessation, Tobacco Use Disorder, United States, United States Food and Drug Administration, e-cigarettes, electronic nicotine delivery, heat-not-burn, nicotine, tobacco, Nicotiana, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences

الوصف: Electronic nicotine delivery systems (ENDS) such as e-cigarettes and heated tobacco products are novel battery-operated devices that deliver nicotine without combustion of tobacco. Because cigarette smoking is sustained by nicotine addiction and the toxic combustion products are mainly responsible for the harmful effects of smoking, ENDS could be used to promote smoking cessation while exposing users to lower levels of toxicants compared with conventional cigarettes. The currently available evidence from clinical and observational studies indicates a potential role of e-cigarettes as smoking cessation aids, although many continue to use e-cigarettes long after quitting smoking. Nicotine and toxicant delivery vary considerably by device and depend on the characteristics of the e-liquid formulation. Because smokers tend to titrate their nicotine intake to maintain their desired pharmacologic effects, device and liquid characteristics need to be considered when using ENDS as an aid to quit smoking. Factors potentially limiting their use are the currently still unknown long-term safety of these products and concerns regarding widespread use among youth. Implications of clinical pharmacology data on ENDS for the cigarette endgame and regulation by the U.S. Food and Drug administration are discussed.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/2rn194cnTest

المؤلفون: St.Helen, Gideon, Benowitz, Neal L, Ko, Jennifer, Jacob, Peyton, Gregorich, Steven E, Pérez-Stable, Eliseo J, Murphy, Sharon E, Hecht, Stephen S, Hatsukami, Dorothy K, Donny, Eric C

المصدر: Journal of Exposure Science & Environmental Epidemiology. 31(2)

مصطلحات موضوعية: Public Health, Health Sciences, Prevention, Tobacco, Tobacco Smoke and Health, Cancer, Good Health and Well Being, Adult, Biomarkers, Carcinogens, Cotinine, Humans, Nitrosamines, Smokers, Tobacco Products, United States, Volatile Organic Compounds, Racial differences, tobacco-related disparities, volatile organic compounds, acrolein, Chemical Sciences, Environmental Sciences, Medical and Health Sciences, Epidemiology, Public health

الوصف: ObjectiveIt is unclear why Black smokers in the United States have elevated risk of some tobacco-related diseases compared to White smokers. One possible causal mechanism is differential intake of tobacco toxicants, but results across studies are inconsistent. Thus, we examined racial differences in biomarkers of toxic volatile organic compounds (VOCs) present in tobacco smoke.MethodWe analyzed baseline data collected from 182 Black and 184 White adult smokers who participated in a randomized clinical trial in 2013-2014 at 10 sites across the United States. We examined differences in urinary levels of ten VOC metabolites, total nicotine equivalents (TNE), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), controlling for covariates such as cigarettes per day (CPD), as well as differences in VOCs per TNE to assess the extent to which tobacco exposure, and not metabolic factors, accounted for racial differences.ResultsConcentration of metabolites of acrolein, acrylonitrile, ethylene oxide, and methylating agents were significantly higher in Blacks compared to Whites when controlled for covariates. Other than the metabolite of methylating agents, VOCs per TNE did not differ between Blacks and Whites. Concentrations of TNE/CPD and VOCs/CPD were significantly higher in Blacks. Menthol did not contribute to racial differences in VOC levels.ConclusionsFor a given level of CPD, Black smokers likely take in higher levels of acrolein, acrylonitrile, and ethylene oxide than White smokers. Our findings are consistent with Blacks taking in more nicotine and toxicants per cigarette smoked, which may explain their elevated disease risk relative to other racial groups.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5mg5j52hTest

المؤلفون: Benowitz, Neal L, St.Helen, Gideon, Nardone, Natalie, Addo, Newton, Zhang, Junfeng, Harvanko, Arit M, Calfee, Carolyn S, Jacob, Peyton

المصدر: Journal of the American Heart Association. 9(23)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Tobacco, Clinical Research, Tobacco Smoke and Health, Substance Misuse, Cardiovascular, Heart Disease, Prevention, Good Health and Well Being, Adult, Biomarkers, Blood Pressure, Catecholamines, Cigarette Smoking, Circadian Rhythm, Cross-Over Studies, Electronic Nicotine Delivery Systems, Female, Heart Rate, Humans, Male, Middle Aged, Nicotine, Oxidative Stress, Platelet Aggregation, Vaping, biomarkers, electronic cigarettes, nicotine, tobacco, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology

الوصف: Background Cardiovascular safety is an important consideration regarding the benefits versus risks of electronic cigarette use (EC) for public health. The single-use cardiovascular effects of EC have been well studied but may not reflect effects of ad libitum use throughout the day. We aimed to compare the circadian hemodynamic effects as well as 24-hour biomarkers of oxidative stress, and platelet aggregation and inflammation, with ad libitum cigarette smoking (CS) versus EC versus no tobacco product use. Methods and Results Thirty-six healthy dual CS and EC users participated in a crossover study in a confined research setting. Circadian heart rate, blood pressure and plasma nicotine levels, 24-hour urinary catecholamines, 8-isoprostane and 11-dehydro-thromboxane B2, and plasma interleukin-6 and interleukin-8 were compared in CS, EC, and no nicotine conditions. Over 24 hours, and during daytime, heart rate and blood pressure were higher in CS and EC compared with no tobacco product conditions (P

الوصول الحر: https://escholarship.org/uc/item/29j4m1j5Test

المؤلفون: St.Helen, Gideon, Nardone, Natalie, Addo, Newton, Dempsey, Delia, Havel, Christopher, Jacob, Peyton, Benowitz, Neal L

المصدر: Addiction. 115(4)

مصطلحات موضوعية: Biological Psychology, Psychology, Tobacco, Tobacco Smoke and Health, Substance Misuse, Clinical Research, Drug Abuse (NIDA only), Good Health and Well Being, Adult, Affect, Craving, Cross-Over Studies, Electronic Nicotine Delivery Systems, Female, Humans, Male, Nicotine, San Francisco, Smoking, Substance Withdrawal Syndrome, Tobacco Products, Dual users, e-cigarettes, e-cigarette dependence, JUUL PK profile, subjective effects, nicotine pharmacokinetics, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Public health, Clinical and health psychology

الوصف: AimTo describe systemic nicotine exposure and subjective effects of electronic cigarettes (e-cigarettes) in people who use both e-cigarettes and cigarettes (dual users), including within-subject comparisons of e-cigarette and cigarette use.DesignTwo-arm, counterbalanced cross-over study. Participants used their usual brand of e-cigarette or cigarette during a standardized session in a 2-week study.SettingHospital research ward, San Francisco, CA, USA.ParticipantsThirty-six healthy (eight women, 28 men) participants.MeasurementsPlasma nicotine was analyzed by gas chromatography-tandem mass spectrometry; nicotine withdrawal, urge to smoke and vape, affective states, craving, satisfaction and psychological reward were measured by standardized questionnaires.FindingsCompared with cigarettes, average maximum plasma nicotine concentration (Cmax ) was lower with e-cigarettes [6.1 ± 5.5 ng/ml, mean ± standard deviation (SD) versus 20.2 ± 11.1 ng/ml, P

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3f2870qqTest

المؤلفون: St.Helen, Gideon, Jacob, Peyton, Nardone, Natalie, Benowitz, Neal L

المصدر: Tobacco Control. 27(Suppl 1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Public Health, Health Sciences, Tobacco, Cancer, Tobacco Smoke and Health, Prevention, Good Health and Well Being, Aerosols, Biomarkers, Humans, Randomized Controlled Trials as Topic, Tobacco Industry, Tobacco Products, electronic nicotine delivery devices, harm reduction, non-cigarette tobacco products, smoking caused disease, tobacco industry

الوصف: BackgroundNew electronic heated tobacco products are being introduced in the global market and are gaining popularity. In 2016, Philip Morris International, Inc. (PMI) submitted a modified risk tobacco product (MRTP) application to the Food and Drug Administration (FDA) to market IQOS in the USA with claims of reduced exposure and reduced risk.MethodsWe examined PMI's MRTP application, specifically sections on aerosol chemistry and human exposure assessment, to assess the validity of PMI's claims of reduced exposure and risk.FindingsPMI reported levels for only 40 of 93 harmful and potentially harmful constituents (HPHCs) on FDA's HPHC list in IQOS mainstream aerosol. All substances in PMI's list of 58 constituents (PMI-58) were lower in IQOS emissions compared with mainstream smoke of 3R4F reference cigarettes. However, levels of 56 other constituents, which are not included in the PMI-58 list or FDA's list of HPHCs, were higher in IQOS emissions; 22 were >200% higher and seven were >1000% higher than in 3R4F reference cigarette smoke. PMI's studies also show significantly lower systemic exposure to some HPHCs from use of IQOS compared with smoking combustible cigarettes.ConclusionPMI's data appear to support PMI's claim that IQOS reduces exposure to HPHCs. However, PMI's data also show significantly higher levels of several substances that are not recognised as HPHCs by the FDA in IQOS emissions compared with combustible cigarette smoke. The impact of these substances on the overall toxicity or harm of IQOS is not known.

الوصول الحر: https://escholarship.org/uc/item/63j485nnTest

المؤلفون: Havel, Christopher M, Benowitz, Neal L, Jacob, Peyton, St.Helen, Gideon

المصدر: Nicotine & Tobacco Research. 19(10)

مصطلحات موضوعية: Epidemiology, Public Health, Health Sciences, Tobacco, Tobacco Smoke and Health, Good Health and Well Being, Aerosols, Electronic Nicotine Delivery Systems, Equipment Design, Flavoring Agents, Humans, Nicotine, Smoking Cessation, Vaping, Clinical Sciences, Public Health and Health Services, Marketing, Public health

الوصف: IntroductionCharacterization of aerosols generated by electronic cigarettes (e-cigarettes) is one method used to evaluate the safety of e-cigarettes. While some researchers have modified smoking machines for e-cigarette aerosol generation, these machines are either not readily available, not automated for e-cigarette testing or have not been adequately described. The objective of this study was to build an e-cigarette vaping machine that can be used to test, under standard conditions, e-liquid aerosolization and nicotine and toxicant delivery.MethodsThe vaping machine was assembled from commercially available parts, including a puff controller, vacuum pump, power supply, switch to control current flow to the atomizer, three-way value to direct air flow to the atomizer, and three gas dispersion tubes for aerosol trapping. To validate and illustrate its use, the variation in aerosol generation was assessed within and between KangerTech Mini ProTank 3 clearomizers, and the effect of voltage on aerosolization and toxic aldehyde generation were assessed.ResultsWhen using one ProTank 3 clearomizer and different e-liquid flavors, the coefficient of variation (CV) of aerosol generated ranged between 11.5% and 19.3%. The variation in aerosol generated between ProTank 3 clearomizers with different e-liquid flavors and voltage settings ranged between 8.3% and 16.3% CV. Aerosol generation increased linearly at 3-6V across e-liquids and clearomizer brands. Acetaldehyde, acrolein, and formaldehyde generation increased markedly at voltages at or above 5V.ConclusionThe vaping machine that we describe reproducibly aerosolizes e-liquids from e-cigarette atomizers under controlled conditions and is useful for testing of nicotine and toxicant delivery.ImplicationsThis study describes an electronic cigarette vaping machine that was assembled from commercially available parts. The vaping machine can be replicated by researchers and used under standard conditions to generate e-cigarette aerosols and characterize nicotine and toxicant delivery.

الوصول الحر: https://escholarship.org/uc/item/6nx4m5dbTest

المؤلفون: St.Helen, Gideon, Dempsey, Delia A, Havel, Christopher M, Jacob, Peyton, Benowitz, Neal L

مصطلحات موضوعية: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Tobacco Smoke and Health, Tobacco, Clinical Research, Substance Misuse, Good Health and Well Being, Cross-Over Studies, Electronic Nicotine Delivery Systems, Flavoring Agents, Heart Rate, Humans, Nicotine, Taste, Tobacco Products, E-cigarettes, Flavors, Nicotine delivery, Nicotine pharmacokinetics, E-cigarette pharmacology, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences, Epidemiology

الوصف: ObjectivesTo describe the effect of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes.Methods11 males and 3 females participated in a 3-day inpatient crossover study with strawberry, tobacco, and their usual flavor e-liquid. Nicotine levels were nominally 18mg/mL in the strawberry (pH 8.29) and tobacco (pH 9.10) e-liquids and ranged between 3-18mg/mL in the usual brands (mean pH 6.80). Each day consisted of a 15-puff session followed by 4h of abstinence, then 90min of ad libitum use. Subjects used a KangerTech mini ProTank 3.ResultsAfter 15 puffs, the amount of nicotine inhaled and systemically retained were not significantly different between the strawberry and tobacco e-liquids but plasma AUC(0→180) was significantly higher with the strawberry e-liquid. While not significantly different, Cmax was 22% higher and various early time point AUCs to measure rate of rise of nicotine in blood ranged between 17 and 23% higher with the strawberry e-liquid compared to the tobacco e-liquid. During ad libitum use, systemic exposure to nicotine (AUC(0→90)) was the same for the tobacco and usual brand e-liquids but were both significantly lower than after using the strawberry e-liquid. The usual flavors were more liked and satisfying than the strawberry and tobacco e-liquids.ConclusionFlavors influence nicotine exposure through flavor liking, may affect rate of nicotine absorption possibly through pH effects, and contribute to heart rate acceleration and subjective effects of e-cigarettes. E-cigarette users titrate their nicotine exposure but the extent of titration may vary across flavors.

الوصول الحر: https://escholarship.org/uc/item/1dt1p2dtTest

المؤلفون: Taghavi, Taraneh, St.Helen, Gideon, Benowitz, Neal L, Tyndale, Rachel F

المصدر: Pharmacogenetics and Genomics. 27(4)

مصطلحات موضوعية: Pharmacology and Pharmaceutical Sciences, Biological Sciences, Biomedical and Clinical Sciences, Genetics, Tobacco Smoke and Health, Tobacco, Cancer, Good Health and Well Being, Administration, Intravenous, Black or African American, Cotinine, Genotype, Glucuronosyltransferase, Humans, Minor Histocompatibility Antigens, Mixed Function Oxygenases, Nicotine, Organic Cation Transport Proteins, Organic Cation Transporter 2, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Smoking, African American, cotinine, FMO3, glucuronidation, nicotine, OCT2, pharmacokinetics, UGT2B10, UGT2B17, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences

الوصف: ObjectivesNicotine metabolism rates differ considerably among individuals, even after controlling for variation in the major nicotine-metabolizing enzyme, CYP2A6. In this study, the impact of genetic variation in alternative metabolic enzymes and transporters on nicotine and cotinine (COT) pharmacokinetics and smoking was investigated.MethodsWe examined the impact of UGT2B10, UGT2B17, FMO3, NAT1, and OCT2 variation on pharmacokinetics and smoking (total nicotine equivalents and topography) before and after stratifying by CYP2A6 genotype in 60 African American (AA) smokers who received a simultaneous intravenous infusion of deuterium-labeled nicotine and COT.ResultsVariants in UGT2B10 and UGT2B17 were associated with urinary glucuronidation ratios (glucuronide/free substrate). UGT2B10 rs116294140 was associated with significant alterations in COT and modest alterations in nicotine pharmacokinetics. These alterations, however, were not sufficient to change nicotine intake or topography. Neither UGT2B10 rs61750900, UGT2B17*2, FMO3 rs2266782, nor NAT1 rs13253389 altered nicotine or COT pharmacokinetics among all individuals (n=60) or among individuals with reduced CYP2A6 activity (n=23). The organic cation transporter OCT2 rs316019 significantly increased nicotine and COT Cmax (P=0.005, 0.02, respectively) and decreased nicotine clearance (P=0.05). UGT2B10 rs116294140 had no significant impact on the plasma or urinary trans-3'-hydroxycotinine/COT ratio, commonly used as a biomarker of CYP2A6 activity.ConclusionWe found that polymorphisms in genes other than CYP2A6 represent minor sources of variation in nicotine pharmacokinetics, insufficient to alter smoking in AAs. The change in COT pharmacokinetics with UGT2B10 rs116294140 highlights the UGT2B10 gene as a source of variability in COT as a biomarker of tobacco exposure among AA smokers.

الوصول الحر: https://escholarship.org/uc/item/4df9k4nzTest