Nicotine Reduction: Strategic Research Plan

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Nicotine & Tobacco Research (Impact Factor: 3.3). 10/2012; 15(6). DOI: 10.1093/ntr/nts214
Source: PubMed


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.

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.

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    • "Both studies showed marked variability between subjects, with some rats exhibiting extinction at doses as high as 0.015 mg/kg and others at doses as low as 0.001 mg/kg. More research is needed to examine this range across strains and species, better characterize individual variability, and identify factors that account for that variability (Donny et al., 2014, 2012; Hatsukami et al., 2013a). An important issue related to nicotine reduction is whether and to what extent a compensatory increase in tobacco use and associated disease risk would occur in individuals attempting to maintain their nicotine intake. "
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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.
    Drug and alcohol dependence 04/2015; 151. DOI:10.1016/j.drugalcdep.2015.03.030 · 3.42 Impact Factor
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    • "tobacco-specific nitrosamines). However, they may not be safer in other respects, such as abuse liability (Hatsukami et al., 2012, 2007, 2010; Pederson and Nelson, 2007; Zeller and Hatsukami, 2009). Development of appropriate methodology for premarket evaluation of the relative abuse liability of potential MRTPs and other tobacco products is needed to inform FDA regulatory policy. "
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    ABSTRACT: Preclinical models are needed to inform regulation of tobacco products by the Food and Drug Administration (FDA). Typically, animal models of tobacco addiction involve exposure to nicotine alone or nicotine combined with isolated tobacco constituents (e.g. minor alkaloids). The goal of this study was to develop a model using extracts derived from tobacco products that contain a range of tobacco constituents to more closely model product exposure in humans. This study compared the addiction-related effects of nicotine alone and nicotine dose-equivalent concentrations of aqueous smokeless tobacco extracts on intracranial self-stimulation (ICSS) in rats. Extracts were prepared from Kodiak Wintergreen, a conventional product, or Camel Snus, a potential "modified risk tobacco product". Binding affinities of nicotine alone and extracts at various nicotinic acetylcholine receptor (nAChR) subtypes were also compared. Kodiak and Camel Snus extracts contained levels of minor alkaloids within the range of those shown to enhance nicotine's behavioral effects when studied in isolation. Nonetheless, acute injection of both extracts produced reinforcement-enhancing (ICSS threshold-decreasing) effects similar to those of nicotine alone at low to moderate nicotine doses, as well as similar reinforcement-attenuating/aversive (ICSS threshold-increasing) effects at high nicotine doses. Extracts and nicotine alone also had similar binding affinity at all nAChRs studied. Relative nicotine content is the primary pharmacological determinant of the abuse liability of Kodiak and Camel Snus as measured using ICSS. These models may be useful to compare the relative abuse liability of other tobacco products and to model FDA-mandated changes in product performance standards. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Drug and Alcohol Dependence 12/2014; 147. DOI:10.1016/j.drugalcdep.2014.12.015 · 3.42 Impact Factor
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    • "The latter types of cigarette, once advertised as ‘low tar and nicotine’ or ‘light’ cigarettes, generate low yields in machine tests due to design features such as a faster rate of cigarette burn, increased ventilation and other factors, but do not involve reducing the nicotine content of the cigarette tobacco.2 7 Smokers of such purported low-yield cigarettes are easily able to compensate for these low-yield cigarettes by taking bigger and more frequent puffs, blocking the ventilation holes with their fingers or lips and/or smoking more cigarettes per day.2 7 Reduced nicotine content cigarettes can be designed similarly to regular cigarettes, except for the lower nicotine content. As the nicotine content is decreased in cigarette tobacco, it would be extremely difficult or impossible to absorb substantial levels of nicotine by smoking cigarettes more intensively (ie, by compensatory smoking8 9). "
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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(Suppl 1):i14-i17. DOI:10.1136/tobaccocontrol-2012-050860 · 5.93 Impact Factor
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