DETERMINANTS OF DRUG ABUSE LIABILITY

药物滥用责任的决定因素

• 批准号: 5201700
• 负责人: S J HEISHMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201700
• 关键词: amphetamines; caffeine; central nervous system stimulants; chemical stimulation; combination chemotherapy; dosage; drug abuse; endogenous opioid; ephedrine; euphoria; human subject; phenylephrine; propanols; psychological reinforcement; psychopharmacology; self medication

Psychoactive substances vary considerably in their abuse liability. For example, major tranquilizers typically do not maintain self-administration behavior, whereas smokable forms of nicotine and cocaine are highly addictive. Quantification of the differences among drugs in terms of abuse liability and discovering the mechanisms that underlie these differences is fundamental in the development of safer medications in general and in developing more effective medications for the treatment of addictive disorders. Two strategies for human evaluation of the mechanisms of drug abuse liability are drug discrimination and drug self-administration. Both of these paradigms evolved from animal research, and their application to humans makes it possible to apply animal and human data to identify mechanisms of addiction. Currently, we are using the drug discrimination paradigm to explore the mechanisms underlying the distinction between the high abuse liability profile of stimulants such as amphetamine and the lower abuse liability of other stimulants such as caffeine. In a series of three studies, the subjective and discriminative effects of several stimulant drugs are being investigated that are widely sold via mail order and designed to imitate amphetamine-like stimulants. These so called "look-alike" stimulants contain caffeine alone or combined with one or more sympathomimetic amines, such as ephedrine and phenylpropanolamine (PPA). Little is known about the behavioral pharmacology in humans of the combined effects of these drugs, including effects when individuals exceed the therapeutic dosage in an attempt to achieve amphetamine-like euphoria. These studies, which have recently been completed, are investigating the drugs singly and in combination. Another series of studies in progress is attempting to refine the drug self-administration paradigm to allow more systematic evaluation of the reinforcing effects of opioids. The initial study of opioid self-administration found that as drug dose was increased, responding for drug increased and concurrent responding for money decreased. The results of this study can be extended to evaluate the role of behavioral factors and medications in modulating the reinforcing effects of opioids in future research.

精神活性物质的虐待责任差异很大。 为了 例如，主要的镇静剂通常不维护 自我管理的行为，而尼古丁的吸烟形式和 可卡因高度上瘾。 量化差异 毒品在虐待责任方面并发现了 这些差异的基础对于更安全的发展至关重要 一般药物和开发更有效的药物 上瘾疾病的治疗。 人类的两种策略 评估药物滥用责任机制是药物 歧视和药物自我管理。 这两个范式 从动物研究中演变而来，他们对人类的应用使它成为 可能应用动物和人类数据以确定 瘾。 目前，我们正在使用药物歧视范式来探索 高虐待责任之间区别的基础机制 苯丙胺等兴奋剂和滥用责任较低的概况 其他兴奋剂，例如咖啡因。 在一系列三项研究中， 几种刺激性药物的主观和歧视作用是 正在调查通过邮购广泛出售并设计为 模仿苯丙胺样兴奋剂。 这些所谓的“外观” 兴奋剂单独包含咖啡因或与一个或多个结合 交感神经胺，例如麻黄碱和苯丙醇胺（PPA）。 关于人类的行为药理学知之甚少 这些药物的综合作用，包括当个人何时效果 超过治疗剂量以实现苯丙胺样 欣快。 这些最近已经完成的研究是 单独调查药物。 正在进行的另一系列研究是试图完善药物 自我管理范式以允许对 加强阿片类药物的作用。 阿片类药物的初步研究 自我管理发现，随着药物剂量的增加， 毒品增加并同时响应货币。 这 这项研究的结果可以扩展以评估行为的作用 调节阿片类药物增强作用的因素和药物 在未来的研究中。