NEUROPSYCHOPHARMACOLOGY OF ALTERED CONSCIOUSNESS

描述（由申请人提供）：本申请申请延续研究科学家奖（K05）。最广泛的目标是了解人们为什么服用精神活性药物，预期或期望的效果是什么，可能导致意外或不良后果的原因是什么，以及如何最好地管理或预防不良后果。耐受性和依赖性如何决定药物使用和效果的差异？药代动力学信息对理解药物反应差异有多大用处？在其他NIDA拨款和合同的支持下，人体实验室实验将研究可卡因、甲基苯丙胺、大麻素3,4-亚甲基二氧甲基苯丙胺（MDMA）的药代动力学和药效学以及与其他药物的相互作用。将MDMA及其相关取代苯乙胺的心血管、自主神经、内分泌和主观效应与麦角酸二乙胺（LSD）进行比较。将研究新的治疗药物对可卡因和甲基苯丙胺耐受性和致敏性的改变。氘标记的甲基苯丙胺和四氢大麻酚在头发和汗液中的药代动力学将被表征，以更好地了解头发和汗液作为药物暴露生物标志物的机制和用途。我们将在第一阶段的实验中描述药物的药代动力学和动力学，这些药物正在开发用于兴奋剂和其他药物依赖的药物治疗。在可能的情况下，对心理和行为测量、情绪评估、神经生理和神经化学指标给予同等的重视。重点是理解行为、生理和药理学变量之间的关系。认识到人们很少将药物服用限制在一种药物或一类药物上，开发和应用适合于研究多类药物的研究策略是首选。在可能的情况下，研究药物作用的个体差异的机制和解释。自然发生的和药物引起的疾病之间的关系，例如，抑郁，焦虑状态和精神分裂症或其他精神病是一个感兴趣的话题。这些研究是多学科的。它们只涉及人类志愿者。该研究将进一步了解精神活性药物的使用、健康后果和管理。

DESCRIPTION (provided by applicant): This application requests continuation of a Research Scientist Award (K05). The broadest objectives are to understand why people take psychoactive drugs, what are expected or desired effects, what might account for unexpected or adverse consequences, and how can adverse consequences best be managed or prevented. How might tolerance and dependence determine differences in drug use and effects? How useful is phamacokinetic information for understanding differences in drug response? With support from other NIDA grants and contracts human laboratory experiments will study the pharmacokinetics and pharmacodynamics of cocaine, methamphetamine, cannabinoids 3,4-methylene-dioxymethamphetamine (MDMA) and interactions with other drugs. The cardiovascular, autonomic, neuroendocrine and subjective effects of MDMA and related of substituted phenethylamines will be compared to lysergic acid diethylamide (LSD). Modification of cocaine and methamphetamine tolerance and sensitization by new treatment medications will be studied. The pharmacokinetics of deuterium-labeled methamphetamine and tetrahydrocannabinol in hair and sweat will be characterized to better understand mechanisms and utility of hair and sweat for biomarkers of drug exposure. We will characterize the pharmacokinetics and dynamics of medications under development for pharmacotherapy of stimulant and other drug dependence in Phase I experiments. As possible, equal attention is given to psychological and behavioral measures, assessment of mood, neurophysiological and neurochemical indices. Emphasis is on understanding relationships between behavioral, physiologic and pharmacologic variables. Recognizing that people rarely limit drug taking to a single drug or class of drugs, development and application of research strategies appropriate to the study of multiple classes of drugs is preferred. Where possible, mechanisms and explanations for individual differences in drug effects are studied. Relationships between naturally occurring and drug-induced disorders, for example, depression, anxiety states and schizophrenia or other psychosis is a topic of interest. The studies are multidisciplinary. They involve only human volunteers. The research will further understanding psychoactive drug use, health consequences and management.