Progressive Commercial Cigarette Yield Reduction: Biochemical Exposure and Behavioral Assessment

Department of Medicine, University of California, San Francisco, San Francisco, California, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 04/2009; 18(3):876-83. DOI: 10.1158/1055-9965.EPI-08-0731
Source: PubMed


Mandated reduction of exposure to nicotine and other cigarette toxins has been proposed as a possible national regulatory strategy. However, tapering using lower yield commercial cigarettes may not be effective in reducing nicotine or tar exposure due to compensatory smoking behavior. We examined the effects of gradual reduction of nicotine yield in commercial cigarettes on smoking behavior, with an assessment of nicotine intake and exposure to tobacco smoke toxins.
This 10-week longitudinal study of 20 smokers involved smoking the usual brand followed by different brands with progressively lower machine-determined yields, ranging from 0.9 to 0.1 mg nicotine, each smoked for 1 week. Subjects were followed for 4 weeks after returning to smoking the usual brand (or quitting). Smoking behaviors, biomarkers of tobacco smoke exposure, and cardiovascular effects were measured.
Cotinine and other biomarkers of smoke exposure remained unchanged comparing the usual brand with the 0.4 mg nicotine brands. A 30% to 40% decrease in nicotine, carbon monoxide, and carcinogen exposure comparing 0.1 mg nicotine cigarettes with baseline was observed. Self-efficacy was significantly increased and dependence decreased after tapering.
We confirm prior cross-sectional population and experimental studies showing complete compensation for cigarettes down to the 0.4 mg nicotine range. Nicotine and tobacco toxin exposure were substantially reduced while smoking 0.1 mg nicotine cigarettes. Our data suggest that the degree of nicotine dependence of smokers may be lowered with progressive yield tapering. Gradual tapering of smokers from regular to ultralow nicotine yield commercial cigarettes might facilitate smoking cessation and warrants future research.

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Available from: Susan L Stewart, Dec 20, 2013
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    • "The present study focused on adult rats because the intent was to model the effects of a gradual nicotine reduction policy in established smokers, similar to studies in humans (Benowitz et al., 2012, 2009a). However, a primary question raised by the prospect of nicotine regulation is whether reducing nicotine delivery below the reinforcement threshold in current adult smokers would actually be sufficient to prevent the development of nicotine addiction in adolescents. "
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    ABSTRACT: The FDA is considering reducing the nicotine content in tobacco products as a population-based strategy to reduce tobacco addiction. Research is needed to determine the threshold level of nicotine needed to maintain smoking and the extent of compensatory smoking that could occur during nicotine reduction. Sources of variability in these measures across sub-populations also need to be identified so that policies can take into account the risks and benefits of nicotine reduction in vulnerable populations. The present study examined these issues in a rodent nicotine self-administration model of nicotine reduction policy to characterize individual differences in nicotine reinforcement thresholds, degree of compensation, and elasticity of demand during progressive reduction of the unit nicotine dose. The ability of individual differences in baseline nicotine intake and nicotine pharmacokinetics to predict responses to dose reduction was also examined. Considerable variability in the reinforcement threshold, compensation, and elasticity of demand was evident. High baseline nicotine intake was not correlated with the reinforcement threshold, but predicted less compensation and less elastic demand. Higher nicotine clearance predicted low reinforcement thresholds, greater compensation, and less elastic demand. Less elastic demand also predicted lower reinforcement thresholds. These findings suggest that baseline nicotine intake, nicotine clearance, and the essential value of nicotine (i.e. elasticity of demand) moderate the effects of progressive nicotine reduction in rats and warrant further study in humans. They also suggest that smokers with fast nicotine metabolism may be more vulnerable to the risks of nicotine reduction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · Drug and alcohol dependence
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    • "switch brands . Benowitz et al . ( 2005 ) reported small reductions in nicotine BoEs in spot urine samples ( normalised by creatinine ) but no reductions in NNAL or biomark - ers of pyrene exposure . They concluded that short - term switching to lower yield brands produced no significant reduction in carcin - ogen exposure . In a more recent study Benowitz et al . ( 2009 ) grad - ually switched smokers from their usual brand ( average yields 12 . 1 mg tar , 1 . 05 mg nicotine ) to five brands with progressively re - duced tar and nicotine yields . Each brand was smoked for a period of 1 week and BoEs for nicotine , NNK , pyrenes ( spot urine samples ) and CO were measured ."
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    ABSTRACT: A forced switch to a lower ISO tar yield cigarette was used in a clinical study, conducted in Germany, that compared two methods of estimating exposure to cigarette smoke. Pre- and post-switch estimates of Mouth Level Exposure (MLE) to nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene and acrolein were obtained by chemical analysis of spent cigarette filters for nicotine content. Similarly, pre- and post-switch estimates of uptake of these smoke constituents were achieved by analysis of corresponding urinary biomarkers of exposure (BoE): total nicotine equivalents; total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL); total 1-hydroxypyrene (1-OHP), and 3-hydroxypropyl-mercapturic acid (3-HPMA), plus the nicotine metabolite cotinine, in plasma and saliva. Three hundred healthy volunteers were recruited comprising 100 smokers of each of 9-10 and 4-6 mg ISO tar yield cigarettes and 50 smokers of 1-2mg ISO tar yield cigarettes and 50 non-smokers. Fifty smokers of each of the 9-10 and 4-6 mg ISO tar yield cigarettes took part in the switching aspects of this study whilst the remaining smokers formed non-switching control groups who smoked their usual ISO tar yield cigarette throughout the study. After 5 days, all subjects were admitted into a clinic where baseline measures of MLE and BoE were obtained. The 10mg switching group was then switched to the 4 mg ISO tar yield cigarette and the 4 mg ISO tar yield switching group switched to the 1mg cigarette. Subjects returned home for 12 days, continuing to smoke the supplied cigarettes before being readmitted into the clinic where samples were collected for MLE and BoE analysis. Changes in daily exposure estimates were determined on a group and individual basis for both methods. The pre- to post-switch directional changes in MLEs and their corresponding BoEs were generally consistent and the MLE/BoE relationship maintained. Switching to a lower yield cigarette generally resulted in reductions in exposure with the resultant exposure level being similar to that seen in regular smokers of the lower yield cigarette.
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    • "Avoidance of the aversive aspects of nicotine withdrawal has been hypothesized to contribute to smoking behavior (e.g., Watkins et al. 2000a, b), and nicotine withdrawal severity is a known predictor of cessation success (Hughes 2007; Piasecki et al. 1998, 2003). Although much less studied, withdrawal is also relevant to certain harm reduction interventions (e.g., switching to cigarettes with reduced nicotine yields or reduced nicotine content) in that they can elicit modest withdrawal symptoms due to decreases in nicotine intake (Benowitz et al. 2007, 2009; Hatsukami et al. 2010a; West et al. 1984; Zacny and Stitzer 1988). These findings raise the possibility that withdrawal might motivate increases in smoking in those individuals that exhibit compensation when switching to reduced-nicotine cigarettes . "
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    ABSTRACT: Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced-nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood. The objective of this study was to examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction. Rats were trained for ICSS and NSA (0.06 mg/kg per infusion). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg per infusion were examined. Following reacquisition of NSA (0.06 mg/kg per infusion), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined. Reducing the NSA unit dose produced partial compensation as indicated by the increased infusion rates, but a 35% mean decrease in daily nicotine intake. The magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine seeking during extinction. Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine seeking during early abstinence.
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