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.

摘要：尼古丁被认为是烟草中的主要成瘾成分。因此，尼古丁 烟草产品的含量可以作为开发有效烟草控制的逻辑目标 政策。 Benowitz和Henningfield（B＆H）在其具有里程碑意义的文章中提出，逐渐减少 香烟的尼古丁含量达到阈值上瘾剂量以下 年轻吸烟者中的尼古丁成瘾。 B＆H估计尼古丁成瘾的阈值是 每烟大约0.17毫克递送的尼古丁，并预测尼古丁剂量以下 阈值既不会自我管理也不会维持尼古丁成瘾。虽然提议超过20年 以前，尼古丁加固的估计阈值仍有待仔细地评估 受控人类研究。此类知识的可用性将为您提供更强的科学原理 尼古丁减少方法的潜在风险和益处。这些知识差距部分是由于困难 在评估人类目前可用的尼古丁输送系统中尼古丁的增强作用时。尽管 某些尼古丁输送系统没有可靠的加固（例如尼古丁口香糖或润滑剂），而另一些则没有交付 精确剂量的尼古丁或除尼古丁外（例如烟草或e-）外，还提供许多其他化学物质 香烟）。为了解决这些局限性，我们开发了一种新颖的静脉（IV）尼古丁自我 人类的管理（NSA）模型。静脉注射尼古丁密切模仿药代动力学和行为 烟熏尼古丁的影响，包括加固。该项目的主要目标是将IV NSA用于 估计阈值加强尼古丁的剂量，并为低剂量的尼古丁产生剂量效应曲线 在吸烟者中。该应用还将检查尼古丁增强阈值和剂量效应曲线是否 随性别和尼古丁代谢率而变化。研究样本将是年轻的成年男性， 女性轻巧和间歇性吸烟者（LITS），也称为“芯片”，她们几乎没有成瘾的迹象。 我们提出了一项双盲，安慰剂对照的跨界研究，该研究将注册36名男性和36位女性lits。 吸烟者将参加五次实验会议。在每个会话中，他们将首先采样分配的 尼古丁剂量和安慰剂（盐水）剂量，然后有机会在尼古丁和 安慰剂管理。从这项研究中获得的知识将有助于指导降低的策略 烟草产品的尼古丁含量，以降低其上瘾的潜力。

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