Random nicotine delivery: A novel intervention for smokers

随机尼古丁输送：针对吸烟者的新型干预措施

基本信息

批准号：
8925844
负责人：
JONATHAN FOULDS
金额：
$ 19.08万
依托单位：
PENNSYLVANIA STATE UNIV HERSHEY MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-15 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8925844
关键词：
Abstinence Adult Adverse effects Affective Alcohols American Behavior assessment Brain Brain region Carbon Monoxide Centers for Disease Control and Prevention (U.S.)Cessation of life Chronic Disease Cigarette Clinical Data Corpus striatum structure Cues Data Dissociation Dose Drug Delivery Systems Drug Kinetics Film Functional Magnetic Resonance Imaging Health Human Instruction Intervention Low income Methods Morbidity - disease rate National Institute of Drug Abuse Nicotine Nose Oral Oral cavity Pharmaceutical Preparations Placebos Plasma Procedures Publishing Pump Questionnaires Rattus Relapse Relative (related person)Reporting Rewards Safety Smoke Smoker Students Substance Addiction Taste Perception Technology Testing Time United States Water addiction base cigarette smoking cost craving man mortality new technology nicotine gum nicotine replacement novel novel strategies pre-clinical relating to nervous system response smoking cessation substance abuse treatment twelfth grade

项目摘要

DESCRIPTION (provided by applicant): According to the CDC, cigarette smoking is associated with profound morbidity and mortality. In the United States alone, cigarette smoking is responsible for about 443,000 deaths per year and it costs the nation nearly $200 billion annually. About 20% of all adults smoke in the United States and by 12th grade, 42% of students report having smoked. Unfortunately, cigarette smoking is a disease of chronic relapse. Indeed, smokers will make as many as 20 quit attempts before they are successful and abstinence rates can be as low as 7%, even following nicotine replacement therapy (NRT) with the patch, gum, or nasal spray. As with other addictions, cue-induced craving contributes to relapse following a quit attempt. Along with cue-induced craving and relapse, addicts also suffer from drug-induced devaluation of natural rewards as evidenced by less responding for a sweet in rats and a weaker striatal response to monetary rewards in humans waiting to smoke. Indeed, those subjects (rats and humans) found least responsive to the natural reward are, in turn, most responsive to drug. Here we propose a novel alternative to the steady-state delivery of nicotine (i.e., to the standard patch), for the treatment of cigarette addiction. Specifically, we propose t use an oral film to treat smokers wishing to quit with random, rather than steady-state, delivery of nicotine prior to and following the quit date. On the basis of promising preclinical and clinica data, we hypothesize that, relative to steady state delivery, random nicotine delivery will be safe well-tolerated, and will facilitate smoking cessation, dissociation of nicotine-paired cues from drug, and a reduction in drug-induced devaluation of natural rewards. Specific Aim 1 will test the pharmacokinetics and safety of a range of doses of the nicotine film in human smokers. Specific Aim 2 will test whether smoking cessation is facilitated when human smokers are treated with random vs. steady-state delivery of nicotine before and after the quit date. Finally, Specific Aim 3 will use fMRI and published procedures to test whether random nicotine delivery also will reduce the neural (striatal) response to nicotine-paired cues and augment the neural response to an alternative monetary reward. If our random delivery hypothesis is confirmed, this novel approach will revolutionize treatment of substance abuse and addiction.

描述（由申请人提供）：根据疾病预防控制中心，吸烟与深远的发病率和死亡率有关。仅在美国，吸烟就会每年造成约443,000人死亡，每年造成近2000亿美元的损失。在美国所有成年人中，大约有20％的吸烟，到12年级，有42％的学生报告了吸烟。不幸的是，吸烟是一种慢性复发的疾病。的确，吸烟者在成功之前将进行多达20次退出尝试，即使遵循贴剂，口香糖或鼻喷雾剂，戒酒率也可能低至7％。与其他成瘾一样，提示引起的渴望在退出尝试后有助于复发。除了提示引起的渴望和复发之外，成瘾者还遭受了毒品引起的自然奖励贬值的困扰，这证明了对大鼠甜食的反应较少，而对人类等待吸烟的货币奖励的纹状体反应较弱。实际上，这些受试者（大鼠和人类）发现对自然奖励的反应最低，反过来又对药物的反应最快。在这里，我们提出了一种新颖的替代品，用于治疗香烟成瘾的尼古丁稳态递送（即标准贴片）。具体而言，我们建议使用口服膜来治疗希望以随机而不是稳态递送尼古丁在退出日期之前和稳态递送的吸烟者。在有希望的临床前和临床数据的基础上，我们假设，相对于稳态递送，随机尼古丁的递送将得到良好的耐受性，并将促进戒烟，尼古丁培养的提示与药物的解离，并降低了药物诱导的自然重新降低。特定的目标1将测试人类吸烟者中一系列尼古丁膜的药代动力学和安全性。当人类吸烟者在退出日期之前和之后用随机的尼古丁和稳态递送治疗时，特定的目标2将测试是否促进戒烟。最后，特定的目标3将使用fMRI和已发布的程序来测试随机尼古丁递送是否还会减少对尼古丁生于的提示的神经（纹状体）反应，并增强对替代货币奖励的神经反应。如果我们的随机分娩假设得到证实，这种新颖的方法将彻底改变对药物滥用和成瘾的治疗。