Behavioral Effects of GHB in Healthy Volunteers

描述(申请人提供)：γ-羟基丁酸(GHB)，一种试剂 具有镇静/肌肉松弛特性，用于治疗其他 作为一种娱乐用药，在年轻人中越来越受欢迎 成年人。然而，尽管人们越来越担心它的可用性和潜在的 在美国，对虐待行为的研究很少 GHB的影响。因此，重要的是更好地描述行为 人体内羟基丁酸的药理作用。为此，这三年的主要目标是 应用是开发一种由GHB指导的新型反应药物识别 在人类的程序中，为了检查歧视性刺激， GHB的自我报告表现和心血管效应。在已指示的 新反应药物识别程序，受试者接受培训以 区分一剂GHB和安慰剂。随之而来的是 检查各种药剂以确定这些药剂是否产生效果 类似于训练条件或既不是条件(例如，新的)。这 程序允许同时评估客观行为测量 例如辨别、自我报告和生理反应，提供 影响的广泛的行为特征。然而，首先，GHB的训练剂量为 将在研究1中通过以下方式确定是否被用于歧视范例 评估GHB的自我报告、生理和性能影响 在广泛的剂量范围内。自我报告、生理、观察者和 性能影响将在之前和之后的几个时间点进行评估 药品管理局。研究1的结果将用于确定峰值和 每种剂量下的GHB效应持续时间以及高剂量和低剂量的GHB 具有明显的自我报告效果，同时产生最低限度的行为 作为训练药物刺激物的损害测试在药物鉴别中的应用 程序。然后将进行第二项研究，以检查GHB的影响， GABAB激动剂巴氯芬、苯二氮卓类GABAA激动剂三唑仑和 甲基黄嘌呤刺激剂咖啡因在人类中被训练为区分 在指示的新反应下从安慰剂中获得高或低剂量的GHB 歧视程序。这项研究的结果将有助于 两种不同训练剂量下GHB刺激物的药理学特异性 以及它与自我报告、生理和表现的关系 效果。这项研究还可能建立一种标准的方法来 系统地描述GHB对人类的行为影响。

DESCRIPTION (provided by applicant): Gamma-hydroxybutyric acid (GHB), an agent with sedative/muscle relaxant properties used therapeutically in other countries, has become increasingly popular as a recreational drug among young adults. Yet, despite increasing concern of its availability and potential for abuse in the United States, there is a paucity of research on the behavioral effects of GHB. Thus, of importance is to better characterize the behavioral pharmacology of GHB in humans. To this end, the major aim of this three-year application is to develop a GHB instructed novel-response drug discrimination procedure in humans, in order to examine the discriminative stimulus, self-reported performance and cardiovascular effects of GHB. In the instructed novel-response drug discrimination procedure, subjects are trained to distinguish between a dose of GHB and placebo. Subsequently, the effects of various agents are examined to determine whether these agents produce effects similar to either training condition or neither condition (e.g., novel). This procedure allows for simultaneous assessment of objective behavioral measures such as discrimination, self-reports and physiological responses, providing a wide behavioral profile of effect. First, however, the training doses of GHB to be employed in the discrimination paradigm will be determined in study 1 by assessing the self-reported, physiological and performance effects of GHB across a wide range of doses. Self-reported, physiological, observer, and performance effects will be assessed prior to and several time points following drug administration. The results of study 1 will be used to determine peak and duration of GHB effects at each dose as well as a higher and lower dose of GHB that have discernable self-reported effects while producing minimal behavioral impairment to test as training drug stimuli in the drug discrimination procedure. A second study will then be conducted to examine the effects of GHB, the GABAb agonist baclofen, the benzodiazepine GABAa agonist triazolam, and the methylxanthine stimulant caffeine in humans trained to discriminate either a high or low dose of GHB from placebo under the instructed novel-response discrimination procedure. The results of this study will shed light on the pharmacological specificity of the GHB stimulus at two different training doses as well as its relationship to self-reported, physiological and performance effects. This study will also potentially establish a standard methodology to characterize systematically the behavioral effects of GHB in humans.