Behavioral Effects of GHB in Healthy Volunteers

描述（由申请人提供）：γ-羟基丁酸（GHB），一种制剂 具有镇静/肌肉松弛特性的治疗用药物， 在一些国家，作为一种娱乐性药物， 成年人了然而，尽管人们越来越担心它的可用性和潜力， 在美国，关于虐待行为的研究很少 GHB的影响。因此，重要的是更好地表征行为 人体内伽马-羟丁酸的药理学为此，这三年的主要目标是 应用是开发一个GHB指导的新反应药物的歧视 在人类中，为了检查辨别刺激， 自我报告的表现和GHB的心血管影响。在指示 新反应药物鉴别程序，受试者接受培训， 一剂GHB和安慰剂之间的区别随后， 检查各种试剂以确定这些试剂是否产生效果 类似于任一训练条件或任一条件（例如，novel）.这 程序允许同时评估客观行为措施 例如辨别力、自我报告和生理反应， 影响广泛的行为特征。首先，然而，GHB的训练剂量， 将在研究1中通过以下方式确定 评估伽马-羟丁酸对自我报告的生理和性能影响 剂量范围很广自我报告、生理、观察者和 将在之前和之后的几个时间点评估性能影响 药品监督管理总局.研究1的结果将用于确定峰和 每种剂量以及较高和较低剂量的GHB的作用持续时间 有可辨别的自我报告的影响，同时产生最小的行为 在药物辨别中对测试作为训练药物刺激的损害 procedure.然后将进行第二项研究，以检查伽马-羟丁酸的影响， GABAb激动剂巴氯芬、苯并二氮杂GABAa激动剂三唑仑和 甲基黄嘌呤兴奋剂咖啡因在人类训练，以区分或 根据指导的新反应，从安慰剂中给予高剂量或低剂量的GHB 歧视程序。这项研究的结果将揭示 GHB刺激在两种不同训练剂量下的药理学特异性 以及它与自我报告、生理和表现的关系 方面的影响.这项研究还可能建立一种标准方法， 系统描述伽马-羟丁酸对人类行为的影响。

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.