N L Benowitz

Roswell Park Cancer Institute, Buffalo, NY, United States

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Publications (523)3461.53 Total impact

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    ABSTRACT: We examined homes of hookah-only smokers and nonsmokers for levels of: indoor air nicotine, a marker of secondhand smoke, and indoor surface nicotine, a marker of thirdhand smoke; and child uptake of nicotine, the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and the toxicant acrolein, by analyzing their corresponding metabolites cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNAL-glucuronides (total NNAL) and 3-hydroxypropylmercapturic acid. Data were collected during 3 home visits during a 7-day study period from a convenience sample of 24 households with a child, 5 years or younger. Three child urine samples, and 2 air and surface samples from the living room and the child bedroom, were taken in homes of nonsmokers (n = 5), and hookah-only smokers (n = 19) comprised of daily hookah smokers (n = 8) and weekly/monthly hookah smokers (n = 11). Nicotine levels in indoor air and on surfaces in the child bedrooms in homes of daily hookah smokers were significantly higher than in homes of nonsmokers. Uptake of nicotine, NNK, and acrolein in children living in daily hookah smoker homes was significantly higher than in children living in nonsmoker homes. Uptake of nicotine and NNK in children living in weekly/monthly hookah smoker homes was significantly higher than in children living in nonsmoker homes. Our data provide the first evidence for uptake of nicotine, the tobacco-specific lung carcinogen NNK, and the ciliatoxic and cardiotoxic agent acrolein in children living in homes of hookah smokers. Our findings suggest that daily and occasional hookah use in homes present a serious, emerging threat to children's long-term health.
    Nicotine & Tobacco Research 03/2014; · 2.48 Impact Factor
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    ABSTRACT: Objective: Individuals with serious mental illness (SMI) are dying on average 25 years prematurely. The leading causes are chronic preventable diseases. In the context of a tobacco-treatment trial, this exploratory study examined the behavioral risk profiles of adults with SMI to identify broader interventional needs. Method: Recruited from five acute inpatient psychiatry units, participants were 693 adult smokers (recruitment rate = 76%, 50% male, 45% Caucasian, age M = 39, 49% had income < $10,000) diagnosed with mood disorders (71%), substance-use disorders (63%), posttraumatic stress disorder (39%), psychotic disorders (25%), and attention deficit-hyperactivity disorder (25%). The Staging Health Risk Assessment, the primary measure used in this study, screened for risk status and readiness to change 11 health behaviors, referencing the period prior to acute hospitalization. Results: Participants averaged 5.2 (SD = 2.1) risk behaviors, including smoking (100%), high-fat diet (68%), inadequate fruits/vegetables (67%), poor sleep (53%), physical inactivity (52%), and marijuana use (46%). The percent prepared to change ranged from 23% for tobacco and marijuana to 76% for depression management. Latent class analysis differentiated three risk groups: the global higher risk group included patients elevated on all risk behaviors; the global lower risk group was low on all risks; and a mood and metabolic risk group, characterized by inactivity, unhealthy diet, sleep problems, and poor stress and depression management. The global higher risk group (11% of sample) was younger, largely male, and had the greatest number of risk behaviors and mental health diagnoses; had the most severe psychopathologies, addiction-treatment histories, and nicotine dependence; and the lowest confidence for quitting smoking and commitment to abstinence. Conclusion: Most smokers with SMI engaged in multiple risks. Expanding targets to treat co-occurring risks and personalizing treatment to individuals' multibehavioral profiles may increase intervention relevance, interest, and impact on health. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Health Psychology 01/2014; · 3.83 Impact Factor
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    ABSTRACT: The rates of nicotine metabolism differ widely, even after controlling for genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Genetic variants in an additional nicotine-metabolizing enzyme, flavin-containing monooxygenase (FMO)-3, and an obligate microsomal CYP-supportive enzyme, cytochrome P450 oxidoreductase (POR), were investigated. We examined the impact of FMO3 E158K and POR A503V before and after stratifying by CYP2A6 metabolism group. In 130 nonsmokers of African descent who received 4 mg oral nicotine, FMO3 158K trended toward slower nicotine metabolism in reduced CYP2A6 metabolizers (P=0.07) only, whereas POR 503V was associated with faster CYP2A6 activity (nicotine metabolite ratio) in normal (P=0.03), but not reduced, CYP2A6 metabolizers. Neither FMO3 158K nor POR 503V significantly altered the nicotine metabolic ratio (N=659), cigarette consumption (N=667), or urine total nicotine equivalents (N=418) in smokers of African descent. Thus, FMO3 E158K and POR A503V are minor sources of nicotine metabolism variation, insufficient to appreciably alter smoking.
    Pharmacogenetics and Genomics 01/2014; · 3.61 Impact Factor
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    ABSTRACT: Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered - Thirdhand smoke (THS) - the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.
    PLoS ONE 01/2014; 9(1):e86391. · 3.73 Impact Factor
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    ABSTRACT: Although the early time course of smoking withdrawal effects has been characterized, the clinical significance of early withdrawal symptoms and their predictors are unknown. This study evaluated the relationships of early smoking withdrawal effects with quit attempt outcomes and the rate of nicotine metabolism. Eleven treatment-seeking smokers abstained from smoking for 4hr in the laboratory, before a quit attempt. Withdrawal measures included heart rate, sustained attention, and self-report. Following baseline assessment, withdrawal measures were administered every 30min. At the conclusion of the 4-hr early withdrawal session, participants received a brief smoking cessation intervention and then returned 1 week and 12 weeks later for outcome assessments that included biochemically confirmed smoking abstinence, cigarettes smoked in the past 24hr, and self-reported withdrawal symptoms. The rate of nicotine metabolism was estimated at intake using the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine) measured in saliva. Greater self-reported negative affect and concentration difficulty during early withdrawal, most notably anxiety, were related with poorer quit attempt outcomes. There was some indication that although a faster increase in craving and greater hunger during early withdrawal were associated with more favorable outcomes, a greater decrease in heart rate during this time was associated with poorer outcomes. Faster nicotine metabolism was related to a faster increase in anxiety but a slower increase in craving during early withdrawal. These findings lend support to the clinical significance of early smoking withdrawal effects. The rate of nicotine metabolism may be a useful predictor of early withdrawal symptoms.
    Nicotine & Tobacco Research 12/2013; · 2.48 Impact Factor
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    ABSTRACT: Nicotine, the main addictive ingredient in tobacco, is metabolically inactivated to cotinine primarily by the hepatic enzyme CYP2A6. Considerable genetic variation in the CYP2A6 gene results in large variation in the rates of nicotine metabolism, which in turn alters smoking behaviours (e.g. amount of cigarettes smoked, risk for dependence and success in smoking cessation). The aim of this study was to identify and characterize novel variants in CYP2A6. The CYP2A6 gene from African American phenotypically slow nicotine metabolizers was sequenced and seven novel variants were identified [CYP2A6*39 (V68M), CYP2A6*40 (I149M), CYP2A6*41 (R265Q), CYP2A6*42 (I268T), CYP2A6*43 (T303I), CYP2A6*44 (E390K), CYP2A6*44 (L462P)]. Variants were introduced into a bi-cistronic cDNA expression construct containing CYP2A6 and P450 oxidoreductase and assessed for protein expression, enzymatic activity and stability as evaluated using western blotting and nicotine metabolism. Genotyping assays were developed and allelic frequencies were assessed in 534 African Americans. The variants showed significantly lower protein expression (P<0.001) when compared with the wild-type as well as reduced metabolism of nicotine to cotinine when controlling for cDNA expression using P450 oxidoreductase (P<0.001). The variants also showed reduced stability at 37°C. Allelic frequencies ranged from 0.1 to 0.6% with a collective genotype frequency of 3.2%; the impact in vitro correlated significantly with in-vivo activity (R=0.40-0.48, P<0.05). Together, those with a novel variant had significantly lower nicotine metabolism in vivo than those without genetic variants (P<0.01). Here, we identified a number of novel variants with reduced/loss of CYP2A6 activity, increasing our understanding of CYP2A6 genetic variability.
    Pharmacogenetics and Genomics 12/2013; · 3.61 Impact Factor
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    ABSTRACT: Nondaily smoking has increased among current U.S. smokers in the past decade and is practiced by a significant percentage of smokers. Although research in nondaily smoking has grown, little is known about levels of exposure to tobacco toxicants among nondaily smokers and their variation across ethnic groups. We examined urinary levels of cotinine and a tobacco-specific nitrosamine (NNAL) in community participants. Associations between the biomarker data and smoking characteristics were evaluated using Spearman's correlation analysis. Participants were 28 Blacks, 4 Latinos, and 25 Whites who smoked at least 1 cigarette on 4-24 days in the past 30 days. Participants averaged 3.3 (SD = 2.1) cigarettes per day (cpd) on days smoked, smoked an average of 13.0 (SD = 5.4) days in the past month, and smoked nondaily for 10.5 (SD = 10.5) years. Median levels of creatinine-normalized cotinine and NNAL were 490.9ng/mg and 140.7 pg/mg, respectively. NNAL and cotinine were highly correlated, r = .84; NNAL and cotinine were modestly correlated with cpd, r = .39 and r = .34 (all p values <.05). The number of days smoked per month was not associated with any biomarker levels. Our findings demonstrate that nondaily smokers are, on average, exposed to significant levels of nicotine and carcinogenic nitrosamines, with exposures of 40%-50% of those seen in daily smokers. This level of exposure suggests a significant health risk. Nicotine and carcinogen exposure is most closely related to number of cigarettes smoked per day but not to number of days per month of smoking.
    Nicotine & Tobacco Research 12/2013; · 2.48 Impact Factor
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    ABSTRACT: Context. Bupropion overdose commonly causes generalized seizures and central nervous system depression. Less commonly, cardiotoxicity has been reported. The toxicity of the parent drug compared to its active metabolite hydroxybupropion is uncertain. Case details. A 31-year-old man presented to the emergency department with altered mental status after an intentional overdose of bupropion. Three hours after admission he developed status epilepticus requiring intubation, and 13 h after admission he developed marked widening of the QRS complex and prolongation of the QTc interval. Serial serum bupropion levels peaked with the onset of cardiotoxicity (334 ng/mL) and fell into the therapeutic range within 24 h, which coincided with normalization of his ECG intervals. Levels of the metabolite hydroxybupropion peaked later (4302 ng/mL) and remained elevated even after neurological and cardiotoxic symptoms resolved. Discussion. Cardiotoxicity appears to be caused primarily by bupropion rather than its active metabolite hydroxybupropion.
    Clinical Toxicology 10/2013; · 2.59 Impact Factor
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    ABSTRACT: Particulate matter (PM) derived from tobacco smoke contains numerous toxic substances. Since the PM and gas phase of tobacco smoke may distribute differently in the environment and substances in them may have different human bioavailability, multiple tracers and biomarkers for tobacco smoke constituents are desirable. Nicotelline is a relatively nonvolatile alkaloid present in tobacco smoke, and therefore, it has the potential to be a suitable tracer and biomarker for tobacco smoke-derived PM. We describe experiments demonstrating that nicotelline is present almost entirely in the PM, in both freshly generated cigarette smoke and aged cigarette smoke. An excellent correlation between the mass of nicotelline and the mass of the PM in aged cigarette smoke was found. We also describe experiments suggesting that the main source of nicotelline in tobacco smoke is dehydrogenation of another little-studied tobacco alkaloid, anatalline, during the burning process. We show that nicotelline metabolites can be measured in the urine of smokers and that nicotelline can be measured in house dust from homes of smokers and nonsmokers. We conclude that nicotelline should be useful as a tracer and biomarker for PM derived from tobacco smoke.
    Chemical Research in Toxicology 10/2013; · 3.67 Impact Factor
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    ABSTRACT: The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery. The California Genetic Disease Screening Program provided dried blood spots from 428 newborns delivered in 2001-2003 with known umbilical cord blood cotinine levels. Cotinine in dried blood spots was measured in 6.35--mm punches by using liquid chromatography--tandem mass spectrometry (quantitation limit, 3.1 ng/mL). Repeated measures of cotinine in dried blood spots were highly correlated (R(2) = 0.99, P < 0.001) among 100 dried blood spots with cotinine quantitated in 2 separate punches. Linear regression revealed that cotinine levels in dried blood spots were slightly lower than those in umbilical cord blood and predicted umbilical cord blood cotinine levels well (β = 0.95, R(2) = 0.80, and P < 0.001 for both cotinine levels in log10 scale). When defining active smoking as a cotinine level of 10 ng/mL or more and using umbilical cord blood cotinine as the criterion standard, we found that measurements of cotinine in dried blood spots had high sensitivity (92.3%) and specificity (99.7%) in the prediction of maternal active smoking. Cotinine levels in dried blood spots are an accurate biomarker of maternal smoking close to the time of delivery.
    American journal of epidemiology 09/2013; · 5.59 Impact Factor
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    ABSTRACT: Exposure of adults to secondhand smoke (SHS) has immediate adverse effects on the cardiovascular system and causes coronary heart disease. The current study evaluated brief self-report screening measures for accurately identifying adult cardiology patients with clinically significant levels of SHS exposure in need of intervention. A cross-sectional study conducted in a university-affiliated cardiology clinic and cardiology inpatient service. Participants were 118 non-smoking patients (59% male, mean age=63.6 years, SD=16.8) seeking cardiology services. Serum cotinine levels and self-reported SHS exposure in the past 24 h and 7 days on 13 adult secondhand exposure to smoke (ASHES) items. A single item assessment of SHS exposure in one's own home in the past 7 days was significantly correlated with serum cotinine levels (r=0.41, p<0.001) with sensitivity ≥75%, specificity >85% and correct classification rates >85% at cotinine cut-off points of >0.215 and >0.80 ng/mL. The item outperformed multi-item scales, an assessment of home smoking rules, and SHS exposure assessed in other residential areas, automobiles and public settings. The sample was less accurate at self-reporting lower levels of SHS exposure (cotinine 0.05-0.215 ng/mL). The single item ASHES-7d Home screener is brief, assesses recent SHS exposure over a week's time, and yielded the optimal balance of sensitivity and specificity. The current findings support use of the ASHES-7d Home screener to detect SHS exposure and can be easily incorporated into assessment of other major vital signs in cardiology.
    Tobacco control 08/2013; · 3.85 Impact Factor
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    ABSTRACT: To evaluate associations of treatment and an 'additive genetic efficacy score' (AGES) based on dopamine functional polymorphisms with time to first smoking lapse and point prevalence abstinence at end of treatment among participants enrolled in two randomized clinical trials of smoking cessation therapies. Double-blind pharmacogenetic efficacy trials randomizing participants to active or placebo bupropion. Study 1 also randomized participants to cognitive-behavioral smoking cessation treatment (CBT) or this treatment with CBT for depression. Study 2 provided standardized behavioural support. Two Hospital-affiliated clinics (Study 1), and two University-affiliated clinics (Study 2). N=792 self-identified white treatment-seeking smokers aged ≥18 years smoking ≥10 cigarettes per day over the last year. Age, gender, Fagerström Test for Nicotine Dependence, dopamine pathway genotypes (rs1800497 [ANKK1 E713K], rs4680 [COMT V158M], DRD4 exon 3 Variable Number of Tandem Repeats polymorphism [DRD4 VNTR], SLC6A3 3' VNTR) analyzed both separately and as part of an AGES, time to first lapse, and point prevalence abstinence at end of treatment. Significant associations of the AGES (hazard ratio = 1.10, 95% Confidence Interval [CI] = 1.06-1.14], p=0.0099) and of the DRD4 VNTR (HR = 1.29, 95%CI 1.17-1.41, p=0.0073) were observed with time to first lapse. A significant AGES by pharmacotherapy interaction was observed (β [SE]=-0.18 [0.07], p=0.016), such that AGES predicted risk for time to first lapse only for individuals randomized to placebo. A score based on functional polymorphisms relating to dopamine pathways appears to predict lapse to smoking following a quit attempt, and the association is mitigated in smokers using bupropion.
    Addiction 08/2013; · 4.58 Impact Factor
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    ABSTRACT: The aim of the study was to examine genetic, pharmacokinetic and demographic factors that influence sensitivity to nicotine in never smokers. Sixty never smokers, balanced for gender and race (Caucasian, Blacks and Asian), wore 7 mg nicotine skin patches for up to 8 hours. Serial plasma nicotine concentrations and subjective and cardiovascular effects were measured, and genetic variation in the CYP2A6 gene, the primary enzyme responsible for nicotine metabolism, was assessed. Nicotine toxicity requiring patch removal developed in 9 subjects and was strongly associated with rate of rise and peak concentrations of plasma nicotine. Toxicity, subjective and cardiovascular effects of nicotine were associated with the presence of reduced function CYP2A6 alleles, presumably reflecting slow nicotine metabolic inactivation. This study has implications for understanding individual differences in responses to nicotine medications, particularly when the latter are used for treating medical conditions in non-smokers, and possibly in vulnerability to developing nicotine dependence.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 9 August 2013 doi:10.1038/clpt.2013.159.
    Clinical Pharmacology &#38 Therapeutics 08/2013; · 6.85 Impact Factor
  • Neal L Benowitz, Maciej L Goniewicz
    JAMA The Journal of the American Medical Association 07/2013; · 29.98 Impact Factor
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    ABSTRACT: BACKGROUND: African Americans are at risk of inadequate adherence to smoking cessation treatment, yet little is known about what leads to treatment discontinuation. PURPOSE: The purpose of this study was to examine the factors associated with discontinuation of treatment in African American light smokers (≤10 cigarettes per day). METHODS: Bupropion plasma levels and counseling attendance were measured among 540 African American light smokers in a placebo-controlled randomized trial of bupropion. RESULTS: By week 3, 28.0 % of subjects in the bupropion arm had discontinued bupropion, and only moderate associations were found between the plasma levels and self-reported bupropion use (r s = 0.38). By week 16, 36.9 % of all subjects had discontinued counseling. Males had greater odds of discontinuing medication (OR = 2.02, 95% CI = 1.10-3.71, p = 0.02), and older adults had lower odds of discontinuing counseling (OR = 0.96, 95% CI = 0.94-0.97, p < 0.0001). CONCLUSIONS: Bupropion and smoking cessation counseling are underutilized even when provided within the context of a randomized trial. Future research is needed to examine strategies for improving treatment utilization among African American smokers. Trial Registration No. NCT00666978 ( www.clinicaltrials.gov ).
    Annals of Behavioral Medicine 06/2013; · 4.20 Impact Factor
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    ABSTRACT: The formation of cotinine, the main proximate metabolite and a biomarker of nicotine exposure, is mediated primarily by CYP2A6. Our aim was to determine if higher cotinine levels in young children exposed to secondhand smoke (SHS) are a result of age-related differences in pharmacokinetics. Forty-nine participants, 2 to 84 months old, received oral deuterium-labeled cotinine, with daily urine samples for up to 10 days for cotinine half-life measurement. DNA from saliva was used for CYP2A6 genotyping. The estimate of half-life using a mixed effect model was 17.9 hrs (95%CI: 16.5, 19.3), similar to that reported in adults. There was no statistically significant effect of sex, race, age, or weight. Children with normal activity CYP2A6*1/*1 genotypes had a shorter half-life than those with 1-2 reduced activity variant alleles. Our data suggest that higher cotinine levels in SHS-exposed young children compared to adults are due to greater SHS exposure rather than different cotinine pharmacokinetics.Clinical Pharmacology & Therapeutics (2013); accepted article preview online 29 May 2013. doi:10.1038/clpt.2013.114.
    Clinical Pharmacology &#38 Therapeutics 05/2013; · 6.85 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Gene variants in CHRNA5-A3-B4, which encode for the α5, α3 and β4 nicotinic receptor subunits, are associated with altered smoking behaviors in European-Americans. Little is known about CHRNA5-A3-B4 and its association with smoking behaviors and weight in Alaska-Native people, which is a population with high prevalence but low levels of tobacco consumption, extensive smokeless tobacco use, and high rates of obesity. We investigated CHRNA5-A3-B4 haplotype structure and its association with nicotine intake and obesity in Alaska-Native people. DESIGN, SETTING, PARTICIPANTS: A cross sectional study of 400 Alaska-Native individuals including 290 tobacco users. MEASUREMENTS: CHRNA5-A3-B4 genotype, body weight, and tobacco consumption biomarkers such as plasma cotinine and urinary total nicotine equivalents (TNE). FINDINGS: Alaska-Native people have a distinct CHRNA5-A3-B4 haplotype structure compared with European/African-Americans. In 290 Alaska-Native tobacco users, the 'G' allele of rs578776, which tagged a 30kb haplotype in CHRNA5-A3-B4, was prevalent (16%) and significantly associated with nicotine intake (20% higher plasma cotinine, P<0.001, 16% higher TNE, P=0.076), while rs16969968 was not associated with nicotine intake. Rs578776 acted in combination with CYP2A6, the main nicotine-metabolizing enzyme, to increase nicotine intake by 1.8 fold compared with the low risk group (P<0.001). Furthermore rs2869950, a single nucleotide polymorphism 5' to CHRNB4, was significantly associated with increased body mass index (P<0.01) in the tobacco users even after controlling for differences in nicotine intake (P<0.01). CONCLUSIONS: Genetic variants in CHRNA5-A3-B4 alter nicotine intake and body mass index in a population of Alaska-Native people, who have a distinct haplotype structure, smoking behaviors and prevalence of obesity.
    Addiction 05/2013; · 4.58 Impact Factor
  • Gideon St Helen, Peyton Jacob, Neal L Benowitz
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    ABSTRACT: INTRODUCTION: The nicotine metabolite ratio (NMR), the ratio of trans-3'-hydroxycotinine (3-HC) to cotinine, has been used as a biomarker of the rate of CYP2A6-mediated nicotine metabolism. While stable in smokers who maintain constant smoking consumption, since smoking has been shown to inhibit nicotine metabolism and this inhibition could be mediated by the nicotine in the smoke, NMR could change during nicotine reduction. The objective of this study was to determine the reproducibility (or stability) of plasma NMR in smokers of progressively reduced nicotine content (RNC) cigarettes. METHODS: We analyzed data from subjects in a clinical trial of smoking progressively RNC cigarettes. Plasma NMR in 30 smokers whose plasma cotinine levels had decreased by at least 50% from the use of the first test cigarette (12mg nicotine content) to the final test cigarette (1mg nicotine content) was measured on 4 occasions over a period of 24 weeks. RESULTS: Plasma cotinine and 3-HC decreased by an average of 85% and 84%, respectively, following the use of the first type of RNC cigarette to the last type. Plasma NMR had an average absolute change of 28.5% over the same period. Using repeated measures analysis, changes in plasma NMR over time were not significant with or without controlling for the effects of age, body mass index, gender, and race (p = .24 and p = .23, respectively). The reliability coefficient for repeated measurements of plasma NMR was .72. The average within-subject coefficient of variation for plasma NMR was 21.6% (SD = 12.0%). CONCLUSION: The plasma NMR is relatively stable over time as nicotine levels decline in smokers of progressively RNC cigarettes.
    Nicotine & Tobacco Research 05/2013; · 2.48 Impact Factor
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    Neal L Benowitz, Jack E Henningfield
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    ABSTRACT: Nicotine is highly addictive and is primarily responsible for the maintenance of cigarette smoking. In 1994, Benowitz and Henningfield proposed the idea of federal regulation of the nicotine content of cigarettes such that the nicotine content of cigarettes would be reduced over time, resulting in lower intake of nicotine and a lower level of nicotine dependence. When nicotine levels get very low, cigarettes would be much less addictive. As a result, fewer young people who experiment with cigarettes would become addicted adult smokers and previously addicted smokers would find it easier to quit smoking when they attempt to do so. The regulatory authority to promulgate such a public health strategy was provided by the Family Smoking Prevention and Tobacco Control Act. Although it precludes 'reducing nicotine to zero', the act does not prohibit the Food and Drug Administration from setting standards for cigarette nicotine content that would prevent them from being capable of causing addiction. This paper reviews the assumptions implicit in a nicotine reduction strategy, examines the available data on the feasibility and safety of nicotine reduction, and discusses the public education, surveillance and support services that would be needed for the implementation of such a policy.
    Tobacco control 05/2013; 22 Suppl 1:i14-i17. · 3.85 Impact Factor
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    ABSTRACT: SIGNIFICANCE: Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. MATERIALS AND METHODS: Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. RESULTS: We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. CONCLUSIONS: Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).
    Tobacco control 03/2013; · 3.85 Impact Factor

Publication Stats

15k Citations
3,461.53 Total Impact Points


  • 2013
    • Roswell Park Cancer Institute
      • Department of Health Behavior
      Buffalo, NY, United States
    • Stanford University
      • Stanford Prevention Research Center
      Palo Alto, CA, United States
  • 2006–2013
    • University of Toronto
      • Department of Pharmacology and Toxicology
      Toronto, Ontario, Canada
    • Environmental Science & Research
      Окленд, Auckland, New Zealand
    • IWK Health Centre
      Halifax, Nova Scotia, Canada
    • Johns Hopkins University
      • Department of Biostatistics
      Baltimore, MD, United States
    • University of Texas MD Anderson Cancer Center
      • Department of Epidemiology
      Houston, TX, United States
  • 2000–2013
    • University of California, Los Angeles
      • • Division of Adult Psychiatry
      • • Department of Medicine
      Los Angeles, CA, United States
  • 1998–2013
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 1979–2013
    • University of California, San Francisco
      • • Division of Clinical Pharmacology & Experimental Therapeutics
      • • Division of Cardiology
      • • Division of Hospital Medicine
      • • Department of Physiological Nursing
      • • Department of Pediatrics
      San Francisco, CA, United States
    • San Francisco VA Medical Center
      San Francisco, California, United States
    • Clinical pharmacology of Miami
      Miami, Florida, United States
  • 2012
    • Emory University
      • Department of Behavioral Sciences and Health Education
      Atlanta, Georgia, United States
    • University of Minnesota Twin Cities
      • Department of Family Medicine and Community Health
      Minneapolis, MN, United States
  • 2007–2012
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
    • SRI International
      • Centre for Health Sciences
      Menlo Park, CA, United States
    • Queen's University
      Kingston, Ontario, Canada
  • 2003–2012
    • University of Pennsylvania
      • Department of Psychiatry
      Philadelphia, PA, United States
  • 2011
    • Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele
      Catania, Sicily, Italy
  • 2010–2011
    • University of Oulu
      • Department of Internal Medicine
      Oulu, Oulu, Finland
    • Oulu University Hospital
      Uleoborg, Oulu, Finland
    • University of Birmingham
      • School of Geography, Earth and Environmental Sciences
      Birmingham, ENG, United Kingdom
  • 1995–2011
    • CSU Mentor
      Long Beach, California, United States
  • 2005–2010
    • Rutgers New Jersey Medical School
      • Department of Psychiatry (RWJ Medical School)
      Newark, NJ, United States
    • Instituto Nacional de Salud Pública
      Cuernavaca, Morelos, Mexico
    • South Dakota State University
      Brookings, South Dakota, United States
  • 2009
    • Washington University in St. Louis
      • Department of Psychiatry
      Saint Louis, MO, United States
  • 2006–2009
    • San Diego State University
      • • Graduate School of Public Health
      • • Department of Psychology
      San Diego, CA, United States
  • 2008
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
  • 2006–2008
    • Yale University
      New Haven, Connecticut, United States
  • 1990–2008
    • University of Pittsburgh
      • • Department of Psychiatry
      • • Psychology
      Pittsburgh, PA, United States
  • 2006–2007
    • Columbia University
      • • Department of Sociomedical Sciences
      • • Department of Psychiatry
      New York City, NY, United States
  • 1991–2007
    • National Cancer Institute (USA)
      • • Division of Cancer Control and Population Sciences
      • • Occupational and Environmental Epidemiology
      Bethesda, MD, United States
  • 2003–2005
    • Dokuz Eylul University
      Ismir, İzmir, Turkey
  • 2004
    • Brigham and Women's Hospital
      • Center for Brain Mind Medicine
      Boston, MA, United States
  • 2002
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 1998–2001
    • Shaare Zedek Medical Center
      • Department of Internal Medicine
      Yerushalayim, Jerusalem District, Israel
  • 1988
    • Oregon Health and Science University
      • Department of Pediatrics
      Portland, OR, United States