Nicotine Reinforcement and Aversion in Young Adult Light Smokers

年轻成年轻度吸烟者的尼古丁强化和厌恶

• 批准号: 9491785
• 负责人: Mehmet Sofuoglu
• 金额: $ 52.42万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9491785
• 关键词: Address; Adult; Behavior; Behavioral; Benefits and Risks; Cause of Death; Chemicals; Cigarette; Cotinine; Cross-Over Studies; Development; Dose; Double-Blind Method; Drug Kinetics; Electronic cigarette; Enrollment; Female; Gender; Goals; Hour; Human; Intake; Intravenous; Knowledge; Light; Measures; Metabolic Clearance Rate; Metabolism; Methodology; Modeling; Nicotine; Nicotine Dependence; Nose; Outcome; Patient Self-Report; Pharmaceutical Preparations; Placebos; Psychological reinforcement; Publications; Randomized; Reproducibility; Research; Route; Saline; Sampling; Sampling Studies; Science; Self Administration; Self-Administered; Smell Perception; Smoke; Smoker; System; Taste Perception; Tobacco; Tobacco Dependence; Vision; Youth; addiction; base; experimental study; human model; hydroxycotinine; interest; knowledge base; male; nicotine gum; novel; prevent; public policy on tobacco; reinforcer; young adult

Abstract: Nicotine is considered to be the main addictive ingredient in tobacco. Therefore, the nicotine content of tobacco products may serve as a logical target in the development of effective tobacco-control policies. In their landmark article, Benowitz and Henningfield (B&H) proposed that the gradual reduction of the nicotine content of cigarettes to an amount below the threshold addictive dose could prevent the development of nicotine addiction among young smokers. B&H estimated that the threshold for nicotine addiction is approximately 0.17 mg of delivered nicotine per cigarette and predicted that nicotine doses below this threshold would neither be self-administered nor maintain nicotine addiction. Although proposed over 20 years ago, this estimated threshold for nicotine reinforcement remains to be systematically evaluated by carefully controlled human studies. Availability of such knowledge would provide a stronger scientific rationale for the potential risks and benefits of nicotine reduction approaches. This knowledge gap is partly due to the difficulty in assessing nicotine's reinforcing effects from currently available nicotine delivery systems in humans. While some nicotine delivery systems are not reliably reinforcing (e.g., nicotine gum or lozenge), others do not deliver accurate doses of nicotine or deliver many other chemicals in addition to nicotine (e.g., tobacco or e- cigarettes). To address these limitations, we have developed a novel intravenous (IV) nicotine self- administration (NSA) model for humans. IV nicotine closely mimics both the pharmacokinetics and behavioral effects of smoked nicotine, including reinforcement. The main goal of this project is to use IV NSA for estimating threshold reinforcing doses of nicotine and to generate dose-effect curves for low doses of nicotine in smokers. This application will also examine if the nicotine reinforcement threshold and dose-effect curve varies with gender and with the rate of nicotine metabolism. The study sample will be young adult male and female light and intermittent smokers (LITS), also known as `chippers', who show few or no signs of addiction. We propose a double-blind, placebo-controlled, crossover study that will enroll 36 male and 36 female LITS. Smokers will participate in five experimental sessions. In each session, they will first sample the assigned nicotine dose and the placebo (saline) dose followed by the opportunity to choose between nicotine and placebo administrations. The knowledge gained from this study will be useful in guiding strategies that lower nicotine content of tobacco products in order to reduce their addictive potential.

翻译后摘要：尼古丁被认为是烟草中的主要成瘾成分。因此，尼古丁 烟草制品的含量可以作为制定有效烟草控制的合理目标 施政纲要而在他们的里程碑式的文章中，Benowitz和Henningfield（B&H）提出， 香烟中尼古丁含量低于成瘾阈值剂量可以防止发展 年轻吸烟者中尼古丁成瘾的比例。B&H估计尼古丁成瘾的阈值是 每支香烟递送的尼古丁约为0.17 mg，并预测尼古丁剂量低于此 阈值既不会自我管理，也不会维持尼古丁成瘾。虽然提出了20多年， 以前，尼古丁强化的估计阈值仍然需要系统地评估， 对照人类研究。这些知识的提供将为以下方面提供更有力的科学依据： 尼古丁减少方法的潜在风险和益处。这种知识差距部分是由于 在评估尼古丁的增强效果，从目前可用的尼古丁输送系统在人类。而 一些尼古丁输送系统不能可靠地增强（例如，尼古丁口香糖或锭剂），其他不提供 精确剂量的尼古丁或递送除尼古丁之外的许多其它化学物质（例如，烟草或电子 香烟）。为了解决这些局限性，我们开发了一种新的静脉注射（IV）尼古丁自我- 美国国家安全局（NSA）的人类模型。静脉注射尼古丁密切模拟药代动力学和行为学 吸烟尼古丁的影响，包括强化。该项目的主要目标是使用IV NSA 估计尼古丁的阈值强化剂量并生成低剂量尼古丁的剂量效应曲线 吸烟者。该应用程序还将检查尼古丁强化阈值和剂量-效应曲线 随着性别和尼古丁代谢率的不同而不同。研究样本为年轻成年男性， 女性轻度和间歇性吸烟者（LITS），也被称为“吸烟者”，很少或没有成瘾迹象。 我们提出了一项双盲、安慰剂对照、交叉研究，将招募36名男性和36名女性LITS。 吸烟者将参加五个实验阶段。在每节课中，他们将首先对指定的 尼古丁剂量和安慰剂（生理盐水）剂量，然后有机会在尼古丁和 安慰剂给药。从这项研究中获得的知识将有助于指导降低 烟草制品中的尼古丁含量，以减少其上瘾的可能性。

项目成果

Threshold for the pleasurable effects of nicotine are lower than its reinforcing effects during self-administration.

尼古丁的愉悦效果阈值低于其自我给药期间的增强效果。

• DOI: 10.1037/pha0000556
• 发表时间: 2023
• 期刊: Experimental and clinical psychopharmacology
• 影响因子: 2.3
• 作者: MacLean,RRoss;Eid,Tore;Parida,Suprit;Gueorguieva,Ralitza;DeVito,EliseE;Sofuoglu,Mehmet
• 通讯作者: Sofuoglu,Mehmet

Threshold dose for intravenous nicotine self-administration in young adult non-dependent smokers.

• DOI: 10.1007/s00213-021-05833-8
• 发表时间: 2021-08
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: MacLean RR;DeVito EE;Eid T;Parida S;Gueorguieva R;Sofuoglu M
• 通讯作者: Sofuoglu M