The role of human drug self-administration procedures in the development of medications
The role of human drug self-administration procedures in the development of medications
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DOI：
10.1016/j.drugalcdep.2008.03.001
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发表时间：
2008-07-01
影响因子：
4.2
通讯作者：
Walsh, S. L.
中科院分区：
文献类型：
--
作者：
Comer, S. D.;Ashworth, J. B.;Walsh, S. L.
本综述的目的是说明在药物开发中采用人类自我管理程序的实用性和价值，包括新药物的滥用倾向评估和物质使用障碍的潜在药物疗法的评估。传统上，人类虐待倾向测试主要依赖于通过问卷描述药物作用的主观报告。同样，假定的治疗药物与滥用药物之间的药物相互作用也依赖于这些措施。主观报告受到高度重视，因为它们提供了有关中枢和外周药效特征以及安全性和耐受性的定性和定量信息。然而，自我管理程序直接检查感兴趣的行为，即吸毒。本文(1)回顾了最常用的人类自我给药程序，(2)讨论了在物质使用障碍药物开发背景下主观报告和自我给药的一致性，主要关注阿片类药物和可卡因依赖的开发工作的说明性例子，(3)探讨了应用自我给药程序来评估新型化合物滥用倾向的效用，包括“滥用威慑”制剂(ADF)。此次审查将重点关注阿片类药物和可卡因依赖，因为这两种药物类别都存在来自临床实验室和临床试验研究的丰富数据库。审查的数据表明，药物引起的自我给药变化和主观效果并不总是一致的。因此，结合主观效果对自我给药的评估提供了更全面的情况，可能会提高转化为临床环境的预测有效性。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest-that is, drug taking. The present paper (1) reviews the most commonly used human self-administration procedures, (2) discusses the concordance of subjective reports and self-administration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and (3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including "abuse-deterrent" formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of self-administration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting. (C) 2008 Elsevier Ireland Ltd. All rights reserved.