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Introduction: The Society for Research on Nicotine and Tobacco began in the United States as a scientific organization "to stimulate the generation and dissemination of new knowledge concerning nicotine and tobacco in all its manifestations." Now in its 30th year, the Society is taking on new challenges in tobacco control, nicotine vaping, product regulation, and public policy., Aims and Methods: This Review describes the formative years of the Society from the perspective of researchers who were in leadership positions during that time, documenting how biobehavioral and clinical research in the first 10 years was a continuation of the scientific mission of the 1988 United States Surgeon General's Report on Nicotine Addiction and summarizing organizational innovations during each president's term of office., Conclusions: The Society's promotion of scientific research served as a catalyst for funding, policy, and regulation, setting the stage for its influence and credibility., Implications: This Commentary provides context and an overview of the scientific research and the organizational innovations that occurred during the early years of the Society for Research on Nicotine and Tobacco using publications and available documentation. The Society was able to thrive because biobehavioral research on nicotine addiction provided the scientific underpinnings for the tobacco control enterprise as a whole. The objective of this Commentary is to describe formative events in the Society's history based on the accomplishments of its early leaders., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use., Methods: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1., Results: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%-4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1-62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5-66.4)], among most demographic subgroups., Conclusions: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4., Impact: Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status., (©2023 American Association for Cancer Research.)

Background: Prior work established a measure of tobacco dependence (TD) among adults that can be used to compare TD across different tobacco products. We extend this approach to develop a common, cross-product metric for TD among youth., Methods: One thousand one hundred and forty-eight youth aged 12-17 who used a tobacco product in the past 30 days were identified from 13 651 youth respondents in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study., Findings: Analyses confirmed a single primary latent construct underlying responses to TD indicators for all mutually exclusive tobacco product user groups. Differential Item Functioning analyses supported the use of 8 of 10 TD indicators for comparisons across groups. With TD levels anchored at 0.0 (standard deviation [SD] = 1.0) among cigarette only (n = 265) use group, mean TD scores were more than a full SD lower for e-cigarette only (n = 150) use group (mean = -1.09; SD = 0.64). Other single product use group (cigar, hookah, pipe, or smokeless; n = 262) on average had lower TD (mean = -0.60; SD = 0.84), and the group with the use of multiple tobacco products (n = 471) experienced similar levels of TD (mean = 0.14; SD = 0.78) as the cigarette only use group. Concurrent validity was established with product use frequency among all user groups. A subset of five TD items comprised a common metric permitting comparisons between youth and adults., Conclusion: The PATH Study Youth Wave 1 Interview provided psychometrically valid measures of TD that enable future regulatory investigations of TD across tobacco products and comparisons between youth and adult tobacco product use group., Implications: A measure of tobacco dependence (TD) has been established previously among adults to compare TD across tobacco products. This study established the validity of a similar, cross-product measure of TD among youth. Findings suggest a single latent TD construct underlying this measure, concurrent validity of the scale with product use frequency across different types of tobacco users, and a subset of common items that can be used to compare TD between youth and adults who use tobacco., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bans of menthol characterizing flavor in tobacco products have been enacted in some localities and proposed in the United States for cigarettes. To gather data regarding how restrictions for menthol in cigarettes and e-cigarettes may affect current menthol cigarette smokers, 37 African American menthol smokers participated in a pilot study in which they were asked to abstain (n = 18) or not abstain from menthol cigarettes (n = 19) for 8-weeks. All participants received menthol flavored e-cigarettes for 4 weeks and tobacco flavored e-cigarettes for 4 weeks in random order. Number of cigarettes smoked per day (estimated mean ratio [EMR] = 0.31; 95% CI: 0.13, 0.72) and exhaled CO concentrations (EMR = 0.61; 95% CI: 0.43, 0.88) were lower in the menthol cigarette abstainer group compared to the menthol cigarette non-abstainer group. Those in the menthol cigarette abstainer group reported higher scores on motivation to quit (p = 0.03) and perceived effectiveness of quitting skills (p = 0.02). There were no substantial effects seen in amount smoked or exhaled CO based on flavor of e-cigarettes provided. Higher e-cigarette use (based on reported puffs per day) was reported in the menthol cigarette abstainer (vs. non-abstainer) group (p < 0.01) and also during the 4-week period when provided with menthol (vs. tobacco) e-cigarettes (p < 0.01). These data suggest that the potential of e-cigarettes to reduce tobacco related harm may be enhanced if combined with a ban on menthol flavor in combustible cigarettes. Larger studies are needed to determine the effect of limiting menthol in e-cigarettes on smoking behavior among current menthol smokers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The United States Food and Drug Administration has the authority to reduce the nicotine content in cigarettes to minimal or non-addictive levels and could do so immediately or gradually over time. A large clinical trial compared the two approaches. This secondary analysis assesses abstinence and cessation-related outcomes one month after the trial concluded, when participants no longer had access to very low nicotine content (VLNC) research cigarettes. Smokers not interested in quitting (N = 1250) were recruited for the parent trial from 2014 to 2016 across 10 sites throughout the US and randomized to a 20-week study period during which they immediately switched to VLNC cigarettes, gradually transitioned to VLNC cigarettes with five monthly dose reductions, or smoked normal nicotine research cigarettes (control). At the one-month follow-up, both immediate and gradual reduction resulted in greater mean cigarette-free days (4.7 and 4.6 respectively) than the control group (3.2, both p < .05). Immediate reduction resulted in fewer mean cigarettes per day (CPD = 10.3) and lower Fagerström Test for Cigarette Dependence (FTCD = 3.7) than the gradual (CPD = 11.7, p = .001; FTCD = 3.8, p = .039) and control (CPD = 13.5, p < .001; FTCD = 4.0, p < .001) groups. Compared to controls, gradual reduction resulted in reduced CPD (p = .012) but not FTCD (p = .13). Differences in CO-verified 7-day point-prevalence abstinence were not significant. Findings demonstrate that switching to VLNC cigarettes resulted in reduced smoking and nicotine dependence severity that was sustained for at least a month after the VLNC trial period in smokers who were not interested in cessation. The greatest harm reduction endpoints were observed in those who immediately transitioned to VLNC cigarettes., Competing Interests: Declaration of Competing Interest EMK, XL, JJ, MA PMC, JDR, LGS, ECD, and DKH have nothing to disclose. DJD has served as a paid expert witness in litigation against tobacco companies. JM has provided consulting and marketing research services to GlaxoSmithKline Consumer Healthcare on smoking cessation behavioral support programs. AAS has received grant support through the Pfizer GRAND grant funding program. RV has received compensation for consulting or scientific advisory board service to Canopy Health Innovations Inc., MyMD Pharmaceuticals, Mira Therapeutics Inc., Syqe Medical Ltd., Radicle Science LLC, and WebMD. NLB serves as a consultant to Pfizer and Achieve Life Sciences, companies that market or are developing smoking cessation medications, and has been a paid expert witness in litigation against tobacco companies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Much of the population-based e-cigarette use and cigarette cessation literature is restricted to smokers who have expressed intention to quit smoking, though experimental studies suggest e-cigarette use might motivate some smokers to change their quit intentions. We used U.S. nationally representative data to evaluate whether e-cigarette use by smokers initially not planning to ever quit is associated with change in plans to quit., Methods: Longitudinal Population Assessment of Tobacco and Health (PATH) Study data collected between 2014 and 2019 were analyzed. Main analyses were conducted among adult daily cigarette smokers not currently using e-cigarettes with no plans to ever quit smoking (n = 2366 observations from n = 1532 individuals). Generalized estimating equations were used to evaluate the association between change in e-cigarette use and change in plans to quit smoking within the next six months, over three assessment pairs., Results: Daily cigarette smokers with no plans to quit had a higher rate of change to plan to quit if at follow-up they used e-cigarettes daily (41.4%, 95% CI: 27.1-57.3%) versus not at all (12.4%, 95% CI: 10.6-14.5%; aOR = 5.7, 95% CI: 2.9-11.2). Rate of change to plan to quit did not statistically differ between those who at follow-up used e-cigarettes some days versus not at all., Conclusions: Among adult daily cigarette smokers initially not planning to ever quit, subsequent daily e-cigarette use is associated with subsequent plans to quit smoking. Population-level research on e-cigarette use that is focused on smokers already motivated to quit may limit a complete evaluation of the smoker population., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Importance: Cigarette smokers not planning to quit are often overlooked in population studies evaluating the risk-benefit potential of electronic nicotine delivery products (e-cigarettes)., Objective: To evaluate whether e-cigarette use is associated with discontinuing cigarette smoking among smokers who were initially never planning to quit., Design, Setting, and Participants: This cohort study used US nationally representative data from the longitudinal Population Assessment of Tobacco and Health Study (waves 2-5 conducted between October 2014 and November 2019), with participants evaluated in 3 pairs of interviews. Adult daily cigarette smokers initially not using e-cigarettes and with no plans to ever quit smoking for good (2489 observations from 1600 individuals) were included., Exposures: e-Cigarette use (ie, daily use, nondaily use, or no use) at follow-up interview among smokers not using e-cigarettes at baseline interview., Main Outcomes and Measures: The main outcomes were discontinuation of cigarette smoking (ie, no cigarette smoking) and discontinuation of daily cigarette smoking (ie, no daily cigarette smoking) at follow-up interview. Generalized estimating equations were used to evaluate the association between the exposure and each outcome, controlling for demographic characteristics and cigarettes smoked per day at baseline interview; all estimates were weighted., Results: The weighted population of adult daily cigarette smokers who were not using e-cigarettes and had no plans to ever quit smoking, based on data from 1600 participants, was 56.1% male (95% CI, 53.4%-58.7%), 10.1% Hispanic (95% CI, 8.2%-12.3%), 10.1% non-Hispanic Black (95% CI, 8.7%-11.7%), 75.6% non-Hispanic White (95% CI, 72.9%-78.2%), and 4.2% of other non-Hispanic race (95% CI, 3.3%-5.4%); 29.3% were aged 55 to 69 years (95% CI, 26.2%-32.6%), 8.9% were aged 70 years or older (95% CI, 6.8%-11.5%), 36.8% did not graduate from high school (95% CI, 34.1%-39.6%), 55.2% had an annual household income of less than $25 000 (95% CI, 52.3%-58.1%), 37.6% smoked 20 to 29 cigarettes per day (95% CI, 34.7%-40.6%), and 12.7% smoked 30 or more cigarettes per day (95% CI, 10.9%-14.7%). Overall, 6.2% of the population (95% CI, 5.0%-7.5%) discontinued cigarette smoking. Discontinuation rates were higher among those who used e-cigarettes daily (28.0%; 95% CI, 15.2%-45.9%) compared with not at all (5.8%; 95% CI, 4.7%-7.2%; adjusted odds ratio [aOR], 8.11; 95% CI, 3.14-20.97). Furthermore, 10.7% (95% CI, 9.1%-12.5%) discontinued daily cigarette smoking, with higher rates of discontinuation observed among those who used e-cigarettes daily (45.5%; 95% CI, 27.4%-64.9%) compared with not at all (9.9%; 95% CI, 8.2%-11.8%; aOR, 9.67; 95% CI, 4.02-23.25). Nondaily e-cigarette use was not associated with cigarette discontinuation (aOR, 0.53; 95% CI, 0.08-3.35) or daily cigarette discontinuation (aOR, 0.96; 95% CI, 0.44-2.09)., Conclusions and Relevance: In this cohort study, daily e-cigarette use was associated with greater odds of cigarette discontinuation among smokers who initially had no plans to ever quit smoking. These findings support the consideration of smokers who are not planning to quit when evaluating the risk-benefit potential of e-cigarettes for smoking cessation in the population.

The topic of e-cigarettes is controversial. Opponents focus on e-cigarettes' risks for young people, while supporters emphasize the potential for e-cigarettes to assist smokers in quitting smoking. Most US health organizations, media coverage, and policymakers have focused primarily on risks to youths. Because of their messaging, much of the public-including most smokers-now consider e-cigarette use as dangerous as or more dangerous than smoking. By contrast, the National Academies of Science, Engineering, and Medicine concluded that e-cigarette use is likely far less hazardous than smoking. Policies intended to reduce adolescent vaping may also reduce adult smokers' use of e-cigarettes in quit attempts. Because evidence indicates that e-cigarette use can increase the odds of quitting smoking, many scientists, including this essay's authors, encourage the health community, media, and policymakers to more carefully weigh vaping's potential to reduce adult smoking-attributable mortality. We review the health risks of e-cigarette use, the likelihood that vaping increases smoking cessation, concerns about youth vaping, and the need to balance valid concerns about risks to youths with the potential benefits of increasing adult smoking cessation.

Background: Determine the overall, sex-, and racially/ethnically-appropriate population-level cotinine and total nicotine equivalents (TNE-2, the molar sum of the two major nicotine metabolites) cut-points to distinguish tobacco users from nonusers across multiple definitions of use (e.g., exclusive vs. polytobacco, and daily vs. non-daily)., Methods: Using Wave 1 (2013-2014) of the U.S. Population Assessment of Tobacco and Health (PATH) Study, we conducted weighted Receiver Operating Characteristic (ROC) analysis to determine the optimal urinary cotinine and TNE-2 cut-points, stratified by sex and race/ethnicity., Results: For past 30-day exclusive cigarette users, the cotinine cut-point that distinguished them from nonusers was 40.5 ng/mL, with considerable variation by sex (male: 22.2 ng/mL; female: 43.1 ng/mL) and between racial/ethnic groups (non-Hispanic other: 5.2 ng/mL; non-Hispanic black: 297.0 ng/mL). A similar, but attenuated, pattern emerged when assessing polytobacco cigarette users (overall cut-point = 39.1 ng/mL, range = 5.5 ng/mL-80.4 ng/mL) and any tobacco users (overall cut-point = 39.1 ng/mL, range = 4.8 ng/mL-40.0 ng/mL). Using TNE-2, which is less impacted by racial differences in nicotine metabolism, produced a comparable pattern of results although reduced the range magnitude., Conclusions: Because of similar frequency of cigarette use among polytobacco users, overall cut-points for exclusive cigarette use were not substantially different from cut-points that included polytobacco cigarette use or any tobacco use. Results revealed important differences in sex and race/ethnicity appropriate cut-points when evaluating tobacco use status and established novel urinary TNE-2 cut-points., Impact: These cut-points may be used for biochemical verification of self-reported tobacco use in epidemiologic studies and clinical trials., (©2021 American Association for Cancer Research.)

Objective: It 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., Method: We 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., Results: Concentration 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., Conclusions: For 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.

Background: Relationships between cigarette filter ventilation levels, biomarkers of exposure (BOE) and potential harm (BOPH), and harm perceptions were examined., Methods: Filter ventilation levels in cigarette brands were merged with Wave 1 (2013-2014) Population Assessment of Tobacco Use and Health study. Data were restricted to smokers who reported a usual brand and not regular users of other tobacco products. BOEs included nicotine, tobacco-specific nitrosamines, volatile organic compounds (VOC), and polycyclic aromatic hydrocarbons. BOPHs measured inflammation and oxidative stress. Perceived harm was assessed as self-reported risk of one's usual brand compared with other brands., Results: Filter ventilation ranged from 0.2% to 61.1% ( n = 1,503). Adjusted relationships between filter ventilation and BOE or BOPH were nonsignificant except for VOC N -acetyl-S-(phenyl)-L-cysteine (PHMA) and high-sensitivity C-reactive protein (hsCRP). In pairwise comparisons, PHMA was higher in quartile (Q) 4 (4.23 vs. 3.36 pmol/mg; P = 0.0103) and Q3 (4.48 vs. 3.36 pmol/mg; P = 0.0038) versus Q1 of filter ventilation and hsCRP comparisons were nonsignificant. Adjusted odds of perceiving one's own brand as less harmful was 26.87 (95% confidence interval: 4.31-167.66), 12.55 (3.01-52.32), and 19.18 (3.87-95.02) times higher in the Q2, Q3, and Q4 of filter ventilation compared with Q1 ( P = 0.0037)., Conclusions: Filter ventilation was not associated with BOE or BOPH, yet smokers of higher ventilated cigarettes perceived their brand as less harmful than other brands compared with smokers of lower ventilated cigarettes., Impact: Research to understand the impact of this misperception is needed, and remedial strategies, potentially including a ban on filter ventilation, are recommended., (©2020 American Association for Cancer Research.)

Introduction: We illustrate the differential impact of common analysis approaches to handling urinary creatinine, a measure for urine dilution, on relationships between race, gender, and biomarkers of exposure measured in spot urine., Methods: In smokers, spot urine levels of total nicotine equivalents (TNE, sum of total nicotine, total cotinine, and total 3'-hydroxycotinine) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) overall and per cigarette were examined. Relationships between race (African Americans [AA] n = 373, Whites n = 758) or gender (males n = 629, females n = 502) and TNE or NNAL were examined using the following approaches to handling creatinine: (1) unadjusted/unstandardized; (2) standardization; (3) adjustment as a covariate. Significance was considered at p < .05., Results: Creatinine was higher in AA versus Whites (1.19 vs. 0.96 mg/mL; p < .0001) and in males versus females (1.21 vs. 0.84 mg/mL; p < .0001). Independent of how creatinine was handled, TNE was lower among AA than Whites (TNE ratios AA vs. Whites: 0.67-0.84; p's < .05). Unadjusted TNE per cigarette was higher among AA versus Whites (ratio 1.12; p = .0411); however, the relationship flipped with standardization (ratio 0.90; p = .0360) and adjustment (ratio 0.95; p = .3165). Regarding gender, unadjusted TNE was higher among males versus females (ratio 1.13; p = .0063), but the relationship flipped with standardization (ratio 0.79; p < .0001) or adjustment (ratio 0.89; p = .0018). Unadjusted TNE per cigarette did not differ across gender (ratio 0.98; p = .6591), but lower levels were found in males versus females with standardization (ratio 0.68; p < .0001) and adjustment (ratio 0.74; p < .0001). NNAL displayed similar patterns., Conclusions: Relationships between race, gender, and spot urine levels of biomarkers of exposure can vary greatly based on how creatinine is handled in analyses., Implications: Lack of appropriate methods can lead to discrepancies across reports on variability of urinary biomarkers by race and gender. We recommend that for any analyses of biomarkers of exposure measure in spot urine samples across race, gender, or other population subgroups that differ in urinary creatinine levels, sensitivity analyses comparing the different methods for handling urinary creatinine should be conducted. If methods result in discrepant findings, this should be clearly noted and discussed., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Cyanoethyl mercapturic acid (CEMA) is a urinary metabolite of acrylonitrile, a toxicant found in substantial quantities in cigarette smoke, but not in non-combusted products such as e-cigarettes or smokeless tobacco and rarely in the diet or in the general human environment. Thus, we hypothesized that CEMA is an excellent biomarker of combusted tobacco product use., Aims and Methods: We tested this hypothesis by analyzing CEMA in the urine of 1259 cigarette smokers (urinary cotinine ≥25 ng/mL) and 1191 nonsmokers. The analyses of CEMA and cotinine were performed by validated liquid chromatography-tandem mass spectrometry methods. Logistic regression was fit for log-transformed CEMA to construct the receiver operating characteristic curve., Results: We found that a CEMA cutpoint of 27 pmol/mL urine differentiated cigarette smokers from nonsmokers with sensitivity and specificity greater than 99%. The use of different cotinine cutpoints to define smokers (10-30 ng/mL) had little effect on the results., Conclusions: CEMA is a highly reliable urinary biomarker to identify users of combusted tobacco products such as cigarettes as opposed to users of non-combusted products, medicinal nicotine, or nonusers of tobacco products., Implications: CEMA can be used to distinguish users of combusted tobacco products from non-combusted products such as e-cigarettes, smokeless tobacco, and medicinal nicotine. Levels of CEMA in the urine of people who use these non-combusted products are extremely low, in contrast to cotinine., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite notable progress in recent decades, cigarette smoke persists as a leading cause of premature death and preventable disease. To weaken the link between nicotine reinforcement and the toxicity associated with combusted tobacco, the United States Food and Drug Administration is considering a product standard targeting cigarette nicotine content. In this review, we summarize research assessing the potential impacts of reducing nicotine in cigarettes. Evidence to date suggests cigarette smoking, toxicant exposure and dependence would decline following substantial reductions in nicotine content. However, reduced nicotine content may not eliminate smoking entirely. Regulatory efforts that shape the nicotine and tobacco marketplace should consider that non-nicotine reinforcing factors and decision-making biases can contribute to the value of smoking. The impact of reducing nicotine in cigarettes will likely depend on the alternative nicotine products available to current smokers. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Smoking to reduce negative affect has been identified as a key motivational feature of tobacco use. Our recent work suggests that smoking very low nicotine content (VLNC) cigarettes reduces the relationship between negative affect and smoking behavior over a 6-week period. Here, we sought to extend our findings by evaluating whether a gradual or immediate approach to switching to VLNC cigarettes led to a differential reduction in the relationship between affect and smoking behavior over a longer (20-week) period., Aims and Methods: Participants (n = 1250) were adult smokers from 10 US sites randomized to one of three groups: gradual nicotine reduction (15.5, 11.7, 5.2, 2.4, and 0.4 mg of nicotine per gram of tobacco [mg/g]), immediate nicotine reduction (0.4 mg/g), or standard nicotine content cigarettes (15.5 mg/g; control), for 20 weeks. We examined whether the relationship between affect-both negative and positive-and cigarettes per day differed as a function of reduction group., Results: We found that both negative and positive affect were associated with cigarette consumption in the control group, but not in the gradual or immediate reduction groups across the 20 weeks of exposure., Conclusions: Our results extend previous findings that switching to VLNC cigarettes disrupts the relationship between affect and cigarette consumption by showing that either gradually or immediately reducing cigarette nicotine content achieves this disruption. These findings provide further evidence that switching to VLNC cigarettes reduces nicotine-related reinforcement of cigarette smoking., Implications: These findings support the notion that switching to very low nicotine content cigarettes reduces the association between affect and smoking behavior, and that either a gradual or immediate nicotine reduction approach achieves this reduction. This provides further evidence that switching to very low nicotine content cigarettes weakens reinforcement mechanisms associated with nicotine dependence., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers., Methods: Secondary analysis was conducted on two cross-sectional samples of adult, daily smokers from Wave 1 (2013-2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers. NMR was modeled continuously in secondary analysis., Results: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant., Conclusions: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers., Impact: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco-related disease., (©2020 American Association for Cancer Research.)

Background: Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOE) among SLT users from the Wave 1 (2013-2014) of the Population Assessment of Tobacco and Health (PATH) Study., Methods: Urinary biospecimens were collected from adults ages 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNA), polycyclic aromatic hydrocarbons (PAH), volatile organic compounds (VOC), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison with exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users., Results: In general, SLT users ( n = 448) have significantly higher concentrations of BOE to nicotine, TSNAs, and PAHs compared with never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers., Conclusions: Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared with cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs., Impact: Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern., (©2020 American Association for Cancer Research.)

This Special Issue on nicotine standards in the United States will address many of the questions raised in the Advance Notice of Proposed Rulemaking (ANPRM) through a series of policy commentaries and timely empirical studies across a variety of topic areas within the proposed comprehensive nicotine standards plan. The questions addressed in this issue include: (1) the threshold dose of nicotine (and other constituents) that would lead to minimally addictive cigarettes; (2) the effects of a nicotine product standard in smokers with co-morbidity, youth and young adult smokers, and menthol smokers; (3) a step-down or targeted data approach to reducing nicotine in cigarettes; (4) perceptions and communications about product standards; and (5) requirements associated with the implementation of a nicotine product standard., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Background: Given the diverse cigar market and limited data on biomarker patterns by cigar type, we compared biomarkers of nicotine and tobacco toxicants among cigar smokers and other groups., Methods: Using Wave 1 urinary biomarker data from 5,604 adults in the Population Assessment of Tobacco and Health (PATH) Study, we compared geometric mean concentrations among cigar-only smokers (all cigars and separately for traditional, cigarillo, and filtered cigars), cigarette-only smokers, dual cigar/cigarette smokers, and never users of tobacco. We calculated geometric mean ratios comparing groups with never users adjusting for sex, age, race/ethnicity, education and creatinine., Results: Some day cigar-only smokers had lower biomarker concentrations than every day cigar-only smokers, but higher than never users. Every day cigar-only smokers ( n = 61) had lower TNE-2 (cotinine+trans-3'-hydroxycotinine) compared to every day cigarette-only ( n = 2217; P < 0.0001) and dual cigar/cigarette smokers ( n = 601; P < 0.0001). Several biomarkers, including NNAL (NNK metabolite) and CYMA (metabolite of acrylonitrile), were comparable in these groups. In exploratory analyses, every day filtered cigar-only ( n = 7) smokers had higher biomarker concentrations compared with every day traditional cigar-only smokers ( n = 12) and cigarillo-only smokers ( n = 24). Every day smokers of each cigar type were similar to exclusive cigarette smokers. For some biomarkers, particularly for every day filtered cigar-only smokers, concentrations were higher., Conclusions: For some biomarkers, every day cigar-only smokers were comparable with every day cigarette-only smokers. Exploratory analyses suggest that biomarkers vary by cigar type with every day filtered cigar-only smokers having the highest concentrations., Impact: High exposure to harmful constituents among cigar smokers is a continuing health issue., (©2019 American Association for Cancer Research.)

Introduction: Since 2009, the United States (US) Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has had the authority to regulate the manufacture, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers could play an important role across a number of FDA regulatory activities, including assessing new and modified risk tobacco products and identifying and evaluating potential product standards., Methods: On April 4-5, 2016, FDA/CTP hosted a public workshop focused on biomarkers of potential harm (BOPH) with participants from government, industry, academia, and other organizations. The workshop was divided into five sessions focused on: (1) overview of BOPH; (2) cardiovascular disease (CVD); (3) chronic obstructive pulmonary disease (COPD); (4) cancer; and (5) new areas of research., Results and Conclusions: The deliberations from the workshop noted some promising BOPH but also highlighted the lack of systematic effort to identify BOPH that would have utility and validity for evaluating tobacco products. Research areas that could further strengthen the applicability of BOPH to tobacco regulatory science include the exploration of composite biomarkers as predictors of disease risk, "omics" biomarkers, and examining biomarkers using existing cohorts, surveys, and experimental studies., Implications: This paper synthesizes the main findings from the 2016 FDA-sponsored workshop focused on BOPH and highlights research areas that could further strengthen the science around BOPH and their applicability to tobacco regulatory science.

Introduction: The US Food and Drug Administration (FDA) has purview over tobacco products. To set policy, the FDA must rely on sound science, yet most existing tobacco research methods have not been designed to specifically inform regulation. The NCI and FDA-funded Consortium on Methods Evaluating Tobacco (COMET) was established to develop and assess valid and reliable methods for tobacco product evaluation. The goal of this article is to describe these assessment methods using a US manufactured "snus" as the test product., Methods: In designing studies that could inform FDA regulation, COMET has taken a multidisciplinary approach that includes experimental animal models and a range of human studies that examine tobacco product appeal, addictiveness, and toxicity. This article integrates COMET's findings over the last 4 years., Results: Consistency in results was observed across the various studies, lending validity to our methods. Studies showed low abuse liability for snus and low levels of consumer demand. Toxicity was less than cigarettes on some biomarkers but higher than medicinal nicotine., Conclusions: Using our study methods and the convergence of results, the snus that we tested as a potential modified risk tobacco product is likely to neither result in substantial public health harm nor benefit., Implications: This review describes methods that were used to assess the appeal, abuse liability, and toxicity of snus. These methods included animal, behavioral economics, consumer perception studies, and clinical trials. Across these varied methods, study results showed low abuse-liability and appeal of the snus product we tested. In several studies, demand for snus was lower than for less toxic nicotine gum. The consistency and convergence of results across a range of multi-disciplinary studies lends validity to our methods and suggests that promotion of snus as a modified risk tobacco products is unlikely to produce substantial public health benefit or harm.

Introduction: The majority of cigarettes sold in the United States and abroad feature filter ventilation holes designed to dilute mainstream smoke. Although initially intended to produce a safer cigarette, data instead suggest that filter ventilation increases total harm from smoking. In the present study, we examined the effects of blocking ventilation holes on behavioral economic demand for cigarettes (i.e., consumption as a function of price)., Methods: In a within-subjects design, regular smokers (N = 15) of ventilated cigarettes sampled vent-blocked cigarettes for 3 days. Subsequently, they completed three sessions in which they used an experimental income to purchase vent-blocked and/or control cigarettes across a range of prices. Participants also completed the Drug Effects/Liking Scale., Results: In sessions in which only one cigarette type was available, demand measures were undifferentiated between cigarette types. However, in sessions in which both cigarettes were available at equivalent prices, significantly greater preference for ventilated control cigarettes emerged in demand measures. Regardless of session type, participants also rated vent-blocked cigarettes more poorly in the Drug Effects/Liking Scale (more bad effects, fewer good effects, and less liking, desire, and less likely to use again)., Conclusions: Removing filter ventilation reduced cigarette abuse liability, as measured by behavioral economic demand and the Drug Effects/Liking Scale. However, reduced demand was only apparent when both cigarette types were concurrently available. This selective effect suggests that regulatory action banning filter ventilation would only reduce cigarette consumption when effective substitutes for vent-blocked cigarettes are available., Implications: This preliminary study indicates that regulatory action designed to ban or restrict cigarette filter ventilation may decrease cigarette abuse liability as measured by both behavioral economic demand and self-report measures. However, effects of removing filter ventilation on demand measures appear to depend on concurrent availability of alternative, preferred cigarette types.

This Special Communication discusses the Food and Drug Administration's (FDA's) proposed rule that would limit N -nitrosonornicotine (NNN) levels in smokeless tobacco products. It argues that finalising and implementing this first 'product standard' would mark a significant step forward in the FDA's efforts to reduce tobacco-related harms., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Tobacco exposure is often quantified by serum or saliva concentrations of the primary nicotine metabolite, cotinine. However, average cotinine concentrations are higher in African Americans (AA) compared with Whites with similar smoking levels. Cotinine is metabolized by UGT2B10 and CYP2A6, and low UGT2B10 activity is common in AA, due to the prevalence of a UGT2B10 splice variant. Methods: UGT2B10 activity was phenotyped in 1,446 smokers (34% AA) by measuring the percentage of cotinine excreted as a glucuronide. Urinary total nicotine equivalents (TNE), the sum of nicotine and 6 metabolites, were determined to quantify smoking dose, and cotinine and 3'-hydroxycotinine were quantified in saliva (study 1) or serum (study 2). Results: Ninety-seven smokers (78% AA) were null for UGT2B10 activity, and the saliva and serum cotinine levels, after adjustment for TNE and cigarettes per day (CPD), were 68% and 48% higher in these smokers compared with nonnull smokers ( P < 0.001). After adjustment for TNE and CPD, salivary cotinine was 35% higher, and serum cotinine 24% higher in AA versus White smokers, but with additional adjustment for UGT2B10 activity, there were no significant differences in saliva and serum cotinine concentrations between these two groups. Conclusions: UGT2B10 activity significantly influences plasma cotinine levels, and higher cotinine concentrations in AA versus White smokers (after adjustment for smoking dose) result from lower levels of UGT2B10-catalyzed cotinine glucuronidation by AA. Impact: UGT2B10 activity or genotype should be considered when using cotinine as a tobacco exposure biomarker, particularly in populations such as AA with high frequencies of UGT2B10 nonfunctional variants. Cancer Epidemiol Biomarkers Prev; 26(7); 1093-9. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes., Methods: We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6., Results: A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups., Conclusions: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.).

Smokeless tobacco products sold in the United States vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of smokeless tobacco use versus constituent levels in the smokeless tobacco product in exposure of users to carcinogens. In this study, smokeless tobacco users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and smokeless tobacco use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, smokeless tobacco users recorded the amount and duration of smokeless tobacco use on a daily basis using their diary cards. Results showed that independent of pattern of smokeless tobacco use and nicotine yields, levels of TSNA in smokeless tobacco products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in smokeless tobacco products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer., (©2014 American Association for Cancer Research.)

Urgent action is needed to reduce the harm caused by smoking. Product standards that reduce the addictiveness of cigarettes are now possible both in the U.S. and in countries party to the Framework Convention on Tobacco Control. Specifically, standards that required substantially reduced nicotine content in cigarettes could enable cessation in smokers and prevent future smoking among current non-smokers. Behavioral economics uses principles from the field of microeconomics to characterize how consumption of a reinforcer changes as a function of the unit price of that reinforcer (unit price=cost/reinforcer magnitude). A nicotine reduction policy might be considered an increase in the unit price of nicotine because smokers are paying more per unit of nicotine. This perspective allows principles from behavioral economics to be applied to nicotine reduction research questions, including how nicotine consumption, smoking behavior, use of other tobacco products, and use of other drugs of abuse are likely to be affected. This paper reviews the utility of this approach and evaluates the notion that a reduction in nicotine content is equivalent to a reduction in the reinforcement value of smoking-an assumption made by the unit price approach., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Both the Tobacco Control Act in the U.S. and Article 9 of the Framework Convention on Tobacco Control enable governments to directly address the addictiveness of combustible tobacco by reducing nicotine through product standards. Although nicotine may have some harmful effects, the detrimental health effects of smoked tobacco are primarily due to non-nicotine constituents. Hence, the health effects of nicotine reduction would likely be determined by changes in behavior that result in changes in smoke exposure., Methods: Herein, we review the current evidence on nicotine reduction and discuss some of the challenges in establishing the empirical basis for regulatory decisions., Results: To date, research suggests that very low nicotine content cigarettes produce a desirable set of outcomes, including reduced exposure to nicotine, reduced smoking, and reduced dependence, without significant safety concerns. However, much is still unknown, including the effects of gradual versus abrupt changes in nicotine content, effects in vulnerable populations, and impact on youth., Discussion: A coordinated effort must be made to provide the best possible scientific basis for regulatory decisions. The outcome of this effort may provide the foundation for a novel approach to tobacco control that dramatically reduces the devastating health consequences of smoked tobacco., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Reducing nicotine content in cigarettes and other combustible products to levels that are not reinforcing or addictive has the potential to substantially reduce tobacco-related morbidity and mortality. The authority to reduce nicotine levels as a regulatory measure is provided in the U.S. Family Smoking Prevention and Tobacco Control Act and is consistent with the general regulatory powers envisioned under the relevant articles of the World Health Organization's Framework Convention on Tobacco Control. Many experts have considered reducing nicotine in cigarettes to be a feasible national policy approach, but more research is necessary., Purpose: This article describes proceedings from a conference that had the goals of identifying specific research gaps, describing methods and measures to consider for addressing these gaps, and considering ways to foster collaboration., Results and Conclusion: Identified research gaps included determining the dose of nicotine that would be optimal for reducing and extinguishing cigarette use, examining approaches for reducing nicotine levels in the general and special populations of smokers, understanding how constituents other than nicotine may contribute to the reinforcing effects of tobacco, and identifying unintended consequences to determine ways to mitigate them. Methods that can be used ranged from brain imaging to large human clinical trials. The development and availability of valid biomarkers of exposure and effect are important. Infrastructures to facilitate collaboration need to be established.

Introduction: Information on chemical composition of the new oral "spitless" smokeless tobacco products is scarce, and it is not clear whether there is some variability as a function of purchase place or time due to either unintended or intended manufacturing variations or other conditions., Methods: We analyzed tobacco-specific N-nitrosamines (TSNA) and nicotine in Marlboro Snus, Camel Snus, and dissolvable Camel products Orbs, Sticks, and Strips that were purchased in various regions of the country during the summer of 2010., Results: A total of 117 samples were received from different states representing six regions of the country. Levels of unprotonated nicotine in Marlboro Snus and Camel Snus varied significantly by regions, with the differences between the highest and the lowest average regional levels being relatively small in Marlboro Snus (∼1.3-fold) and large in Camel Snus (∼3-fold). Some regional variations in TSNA levels were also observed. Overall, Camel Snus had significantly higher TSNA levels than Marlboro Snus, and Camel Strips had the lowest TSNA levels among all novel products analyzed here. The amount of unprotonated nicotine in the dissolvable Camel products was comparable to the levels found in Marlboro Snus., Conclusions: Our study demonstrates some regional variations in the levels of nicotine and TSNA in Marlboro and Camel novel smokeless tobacco products. Continued monitoring of this category of products is needed as the existing products are being test marketed and modified, and new products are being introduced. This information is particularly important given its relevance to Food and Drug Administration regulation of tobacco products.

Background: Modification of tobacco curing methods and other changes in cigarette manufacturing techniques could substantially reduce the levels of tobacco-specific nitrosamines (TSNA), a group of potent carcinogens, in cigarette smoke. In 1999, two major US cigarette manufacturers stated their intent to move towards using tobaccos low in TSNA. There is no information available on current TSNA levels in tobacco of various cigarettes available in the US, particularly in the newer varieties introduced over the past decade., Methods: Seventeen brands of cigarettes were purchased in April of 2010 from retail stores in Minnesota. TSNA levels were measured in the tobacco filler and smoke of these cigarettes., Results: In all brands, the sum of two potent carcinogenic TSNA--4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N'-nitrosonornicotine--in cigarette filler averaged 2.54 (± 1.05) μg/g tobacco. This value is virtually identical to the sum of these two carcinogens reported for the tobacco of a US filtered cigarette in 1979. TSNA levels in smoke positively correlated with those in tobacco filler of the same cigarettes., Conclusion: We found no indication that any meaningful attempt was made to reduce or at least control TSNA levels in the new varieties of the popular brands Marlboro and Camel introduced over the last decade. In light of the recently granted regulatory authority to the FDA over tobacco products, regulation of TSNA levels in cigarette tobacco should be strongly considered to reduce the levels of these potent carcinogens in cigarette smoke.

The rate of initiation and progression to dependence and premature mortality are higher for tobacco products than for any other dependence producing substance. This is not explained simply by the addictiveness ("abuse liability") or by enticing product designs ("product appeal") alone, but rather by both of these factors in combination with marketing and social influences that also influence "product appeal". A working meeting of leading experts in abuse liability (AL) and product appeal was convened to examine how these disciplines could be more effectively applied to the evaluation of tobacco products for the purposes of regulation that would include setting standards for designs and contents intended to reduce the risk of initiation and dependence. It was concluded that abuse liability assessment (ALA) is a validated approach to testing pharmaceutical products but has not been extensively applied to tobacco products: such application has demonstrated feasibility, but special challenges include the diverse range of products, product complexity, and the absence of satisfactory placebo products. Consumer testing for product appeal is widely used by consumer product marketers as well as by researchers in their efforts to understand consumer product preferences and use but has not been extensively applied to tobacco products except by the tobacco industry. Recommendations for testing, methods development, and research were developed. A major recommendation was that tobacco products should be tested for AL and product appeal, and the results integrated and evaluated so as to more accurately predict risk of initiation, dependence, and persistence of use., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Regulation of nicotine levels in cigarettes and other tobacco products is now possible with the passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009, giving the US Food and Drug Administration (FDA) authority to regulate tobacco products, and with Articles 9-11 of the WHO Framework Convention on Tobacco Control. Both regulatory approaches allow establishing product standards for tobacco constituents, including nicotine. The FSPTCA does not allow nicotine levels to be decreased to zero, although the FDA has the authority to reduce nicotine yields to very low, presumably non-addicting levels. The proposal to reduce levels of nicotine to a level that is non-addicting was originally suggested in 1994. Reduction of nicotine in tobacco products could potentially have a profound impact on reducing tobacco-related morbidity and mortality. To examine this issue, two meetings were convened in the US with non-tobacco-industry scientists of varied disciplines, tobacco control policymakers and representatives of government agencies. This article provides an overview of the current science in the area of reduced nicotine content cigarettes and key conclusions and recommendations for research and policy that emerged from the deliberations of the meeting members.

Tobacco products are widely sold and marketed, yet integrated data systems for identifying, tracking, and characterizing products are lacking. Tobacco manufacturers recently have developed potential reduced exposure products (PREP) with implied or explicit health claims. Currently, a systematic approach for identifying, defining, and evaluating PREPs sold at the local, state, or national levels in the United States has not been developed. Identifying, characterizing, and monitoring new tobacco products could be greatly enhanced with a responsive surveillance system. This article critically reviews available surveillance data sources for identifying and tracking tobacco products, including PREPs, evaluating strengths and weaknesses of potential data sources in light of their reliability and validity. With the absence of regulations mandating disclosure of product-specific information, it is likely that public health officials will need to rely on a variety of imperfect data sources to help identify, characterize, and monitor tobacco products, including PREPs.

We examined racial/ethnic variations in the use of nicotine replacement therapy (NRT) and quit ratios among Caucasian, African American, Asian, and Latino lifetime smokers ages 25 to 44 years. We conducted cross-sectional analyses using data from individuals (n = 27,031) screened for enrollment in the Collaborative Study of the Genetics of Nicotine Dependence. Participants were randomly sampled from three Midwestern metropolitan areas using Health Maintenance Organization membership lists in Detroit, MI and Minneapolis, MN and a driver's license registry in St. Louis, MO from March 2003 to August 2005. A telephone survey collected information on smoking history, previous quit attempts, and sociodemographic characteristics. Among lifetime smokers (n = 9,216), univariate analysis indicated that African Americans (22%) and Latinos (22%) were significantly less likely to report having ever used NRT for smoking cessation than Caucasians (31%). Asians (22%) also reported lower rates of using NRT than Caucasians, but this difference was marginally significant (P = 0.06). These disparities persisted in multivariate analysis for African Americans [adjusted odds ratio (OR), 0.76; 95% confidence interval (95% CI), 0.63-0.91; P < 0.01] but not for Latinos (adjusted OR, 0.76; 95% CI, 0.54-1.06; P = 0.11) or Asians (adjusted OR, 0.98; 95% CI, 0.60-1.60; P = 0.95). As measured by the quit ratio, African Americans (35%) were less likely to have quit smoking than Caucasians (52%). This disparity persisted in multivariate logistic regression (adjusted OR, 0.66; 95% CI, 0.56-0.78; P < 0.001). Asian and Latino smokers were as likely as Caucasians to report smoking cessation. Future prospective studies are needed to assess whether lower utilization of cessation treatments such as NRT contribute to the observed disparity in quit ratios for African Americans.

This study examined perceived risk of harm from smoking or ST use in a U.S. nationally representative sample of high school seniors and examined its association with current smoking status. Data were derived from the Monitoring the Future project for 1999 through 2003 (n = 11,093). We used multiple logistic regression analysis to examine the association between comparative perceived risk of harm of smoking and ST use with current smoking status, while adjusting for sex, race, and perceived risk of harm from smoking. In 1999-2003, 74.0% of high school seniors perceived great risk of harm from smoking and 44.9% perceived great risk from using ST. Perceived risk varied by smoking intensity: 80.3% of non-smokers perceived great risk of harm from smoking, compared to 49.7% of students who smoked about one-half pack per day and 36.1% of pack-a-day smokers. Overall, 52.7% perceived equal risk of harm from using either product, 41.3% perceived greater risk from cigarettes, and 6.1% perceived a greater risk from using ST. Adjusting for sex and race, high school seniors who perceived that smoking conveyed a greater risk for harm than did using smokeless tobacco were significantly more likely to be smokers than were those who perceived equal risk from the products (odds ratio [OR] = 1.43; 95% confidence interval [CI] 1.29-1.60). Those who perceived that using smokeless tobacco was riskier than smoking were even more likely to be current smokers (OR = 2.43; 95% CI 1.96-3.01). Effective methods for communicating accurate health risks to young people are needed.

Tobacco harm reduction approaches are gaining increased attention. Much of this attention is due to a growing concern that significant populations of smokers either do not want to quit or believe they are unable to quit smoking, and to a concern over tobacco-industry attempts to produce tobacco products that claim to result in less toxin exposure. Decreasing tobacco toxin exposure as a method for reducing mortality and morbidity may be a reasonable tobacco control strategy. However, the impact of this strategy must be explored both on individual and population levels. A significant amount of independent research is needed to inform policy decisions. Regulatory authority over potential reduced exposure products is also essential.

Nicotine addiction has been identified as the primary contributor to continued widespread tobacco use worldwide. Although the health benefits of smoking cessation are well publicized, few smokers successfully quit on a long-term basis. A number of pharmacological agents have been shown to approximately double long-term smoking cessation rates and have, therefore, been recommended as first-line therapy for the treatment of nicotine dependence in the clinical practice guidelines recently released by the Agency for Healthcare Research and Quality (AHRQ). These include the currently available dosage forms of nicotine replacement therapy (gum, patch, nasal spray, and inhaler) and bupropion. Other agents that have exhibited some efficacy in increasing smoking cessation rates are nortriptyline and clonidine. All pharmacological treatments are most effective in conjunction with behavioral therapy. Other approaches to treating tobacco use disorder now being investigated include additional ways to administer nicotine, a vaccine to prevent nicotine from crossing the blood-brain barrier, and agents that alter the metabolism of nicotine. This review summarizes the characteristics of nicotine addiction, reviews the pharmacological agents currently used to treat tobacco use disorder, and describes possible approaches to treat nicotine dependence in the future.

Objective: To review and discuss the differences and similarities between the use of crack cocaine and cocaine hydrochloride; and to determine how these findings might affect policies on the imprisonment and treatment of cocaine users., Data Sources: English-language publications were identified through a computerized search (using MEDLINE) between 1976 and 1996 using the search terms "smoked cocaine," "crack cocaine," "freebase," and "cocaine-base." In addition, manual searches were conducted on references cited in original research articles, reviews, and an annotated bibliography, and on selected journals., Study Selection: Only those articles that compared various routes of cocaine administration or types of cocaine (cocaine base or crack cocaine vs cocaine hydrochloride) were examined., Data Extraction: Studies were reviewed to obtain information on the composition of the 2 forms of cocaine, and the prevalence, pharmacokinetics and pharmacodynamics, abuse liability, pattern of use, and consequences across the various routes of cocaine administration and forms of cocaine., Conclusion: Cocaine hydrochloride is readily converted to base prior to use. The physiological and psychoactive effects of cocaine are similar regardless of whether it is in the form of cocaine hydrochloride or crack cocaine (cocaine base). However, evidence exists showing a greater abuse liability, greater propensity for dependence, and more severe consequences when cocaine is smoked (cocaine-base) or injected intravenously (cocaine hydrochloride) compared with intranasal use (cocaine hydrochloride). The crucial variables appear to be the immediacy, duration, and magnitude of cocaine's effect, as well as the frequency and amount of cocaine used rather than the form of the cocaine. Furthermore, cocaine hydrochloride used intranasally may be a gateway drug or behavior to using crack cocaine. Based on these findings, the federal sentencing guidelines allowing possession of 100 times more cocaine hydrochloride than crack cocaine to trigger mandatory minimum penalties is deemed excessive. Although crack cocaine has been linked with crime to a greater extent than cocaine hydrochloride, many of these crimes are associated with the addiction to cocaine. Therefore, those addicted individuals who are incarcerated for the sale or possession of cocaine are better served by treatment than prison.

There is an increasing prevalence of smokeless tobacco use. However, very little descriptive information is available on the pattern of use. This study examines topographical features of smokeless tobacco use in a male college-age population (N = 56). Subjects were required to use smokeless tobacco ad lib. for a period of 3 days. During this time, they were asked to record the time of onset and completion of each dip of smokeless tobacco. Smokeless tobacco use was significantly associated with time of day. The mean dips/day was 6.3 (SD +/- 2.2), mean inter-dip interval was 102.6 (SD +/- 42.1) min, mean duration/dip was 39.9 (SD +/- 16.5)min, and mean total dip duration/day was 254.6 (SD +/- 129.3) min. The mean grams of tobacco/dip was 1.97 (SD +/- 0.96) and the total grams of tobacco used/day was 12.0 (SD +/- 6.8) g. There were significant correlations between saliva cotinine and number of dips/day, mean duration/dip, total dip duration/day and mean inter-dip interval, suggesting that smokeless tobacco has the potential for producing dependence.