Threshold Dose for Nicotine Discrimination in Cigarettes

香烟中尼古丁歧视的阈剂量

基本信息

批准号：
8573038
负责人：
KENNETH Alan PERKINS
金额：
$ 20.16万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8573038
关键词：
Address Affect Animal Experimentation Area Behavior Behavioral Cigarette Clinical Trials Dependence Development Discrimination Dose Drug Formulations Female Flavoring Health Human Intake Laboratories Lead Maintenance Menthol Methodology Methods Modeling NIH Program Announcements National Institute of Drug Abuse Nicotine Nicotine Dependence Nicotine Nasal Spray Nose Pharmaceutical Preparations Placebos Policies Procedures Psychological reinforcement Public Policy Regulation Research Research Project Grants Risk Sampling Self Administration Smoker Smoking Stimulus Subgroup Testing Tobacco Tobacco Dependence Tobacco use United States National Institutes of Health Vulnerable Populations Woman addiction base cigarette smoking experience interest male men novel policy implication preference prevent programs public health relevance response smoking cessation tobacco control

Address Affect Animal Experimentation Area Behavior Behavioral Cigarette Clinical Trials Dependence Development Discrimination Dose Drug Formulations Female Flavoring Health Human Intake Laboratories Lead Maintenance Menthol Methodology Methods Modeling NIH Program Announcements National Institute of Drug Abuse Nicotine Nicotine Dependence Nicotine Nasal Spray Nose Pharmaceutical Preparations Placebos Policies Procedures Psychological reinforcement Public Policy Regulation Research Research Project Grants Risk Sampling Self Administration Smoker Smoking Stimulus Subgroup Testing Tobacco Tobacco Dependence Tobacco use United States National Institutes of Health Vulnerable Populations Woman addiction base cigarette smoking experience interest male men novel policy implication preference prevent programs public health relevance response smoking cessation tobacco control

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项目摘要

DESCRIPTION (provided by applicant): The lowest (i.e. threshold) nicotine dose in cigarettes that produces tobacco reinforcement and dependence is almost certainly not lower than the threshold dose for discrimination of nicotine's interoceptive stimulus effects from smoking. Despite a half century of animal research on nicotine discrimination and prior human studies of threshold dose for discriminating drugs other than nicotine, no research has clearly assessed this nicotine discrimination threshold in humans via cigarettes because of difficulty controlling nicotine dosing with tobacco intake. Because our lab has, by far, the most experience assessing nicotine discrimination in humans (including threshold dose, with a nicotine formulation other than tobacco), we propose to employ well- validated behavioral discrimination methodology to identify the cigarette nicotine threshold dose for discrimination using nicotine research cigarette (NRC) from the NIDA Drug Supply Program. We will assess threshold doses in a diverse sample of 100 healthy male and female smokers varying in dependence level and menthol preference to generate evidence that informs policy on establishing a maximum nicotine content in tobacco cigarettes that could prevent the onset and maintenance of dependence. We hypothesize that this nicotine threshold dose for discrimination will be lower than the yield of most current commercial brands, which typically exceed 0.4 mg. We also hypothesize that the threshold dose will be lower in nondependent vs. dependent smokers, in men vs. women, and perhaps as a function of cigarette menthol preference, consistent with prior research on differences in nicotine sensitivity. Importantly, this study will also separately assess self-administration of nicotine from these cigarettes to determine the relationship between nicotine discrimination threshold dose and reinforcement threshold dose in smoking. This research is highly significant because limiting nicotine cigarettes to amounts below this threshold dose could minimize risk of nondependent smokers escalating to dependence and make it easier for dependent smokers to quit smoking. As such, this R21 addresses key research objectives of the FDA's Center for Tobacco Products (CTP), notably those involving reducing addiction to tobacco products by modifying nicotine levels, including in potentially vulnerable populations, and adverse health consequences of tobacco use.

描述（由申请人提供）：在香烟中最低（即阈值）尼古丁剂量产生烟草增强和依赖性，几乎肯定不低于识别尼古丁的互感刺激效果的阈值剂量。尽管有半个世纪的动物研究对尼古丁歧视和先前对阈值剂量的人类研究，用于歧视尼古丁以外的其他药物，但由于难以通过烟草摄入来控制尼古丁给药，因此没有清楚地通过香烟评估了人类的这种尼古丁歧视阈值。由于我们的实验室拥有评估人类尼古丁歧视的最多经验（包括阈值剂量，除烟草以外的尼古丁配方），因此我们建议采用良好验证的行为歧视方法，以识别尼古丁研究烟（NRC）从NIDA药物供应计划中识别烟气尼古丁阈值剂量，以识别烟气中的尼古丁阈值剂量。我们将评估100个健康男性和女性吸烟者的不同样本中的阈值剂量，这些依赖性水平和薄荷醇优先级别，以产生证据，以告知政策，以在烟草香烟中建立最大的尼古丁含量，以防止依赖的发作和维持。我们假设这种歧视的尼古丁阈值剂量将低于大多数当前商业品牌的产量，该品牌通常超过0.4 mg。我们还假设，在非依赖性和依赖吸烟者，男性与女性中，阈值剂量将较低，并且可能是烟薄荷质偏爱的函数，这与先前对尼古丁敏感性差异的研究一致。重要的是，这项研究还将分别评估尼古丁与这些香烟的自我给药，以确定尼古丁歧视阈值剂量和增强阈值在吸烟中的关系。这项研究非常重要，因为将尼古丁香烟限制为低于此阈值剂量的量可以最大程度地降低非依赖性吸烟者升级以依赖的风险，并使依赖吸烟者更容易戒烟。因此，该R21解决了FDA烟草产品中心（CTP）的关键研究目标，尤其是那些涉及减少烟草产品的成瘾的烟碱水平，包括潜在易受伤害的人群以及烟草使用的不良健康后果。