Behavioral Effects of GHB in Healthy Volunteers

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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.