NEUROPSYCHOPHARMACOLOGY OF ALTERED CONSCIOUSNESS

这是一项延续研究科学家奖的请求。 我最广泛的目标是理解为什么人们会 精神活性药物，通常和预期的效果是什么， 可能导致意想不到的后果，以及如何可能 最好的办法是控制不良后果。例如，如何 耐受性和依赖性决定药物的个体差异 使用和药物影响？个别计划研究 可卡因和可卡因的药代动力学和药效学 甲基苯丙胺通过各种途径给药，他们的 与乙醇的相互作用。药物动力学和药动学 心血管、自主神经、脑电、神经内分泌和主观 取代苯乙胺对3，4-亚甲基的影响 二氧甲基苯丙胺(MDMA)和相关化合物将 与麦角酸二乙胺(LSD)相比，甲基苯丙胺 还有可卡因。修改关联的容忍度和依赖性 可卡因和甲基苯丙胺的使用 将研究新的治疗药物。药代动力学 氢气标记的可卡因、可卡因、吗啡和 头发、皮肤、汗液、皮脂和血浆中的甲基苯丙胺- 其特点是更好地理解药物的作用机制 进入毛发并判断毛发和汗液分析的实用性 毒品暴露的生物标志物。刻画人物形象 丁丙诺啡及其代谢物的药代动力学 与纳洛酮的相互作用和改变这种影响的因素是 作为新药物治疗评估的一部分进行研究 用于鸦片、可卡因和相关依赖。尽可能地，平等 关注心理和行为测量， 情绪、神经生理和神经化学的评估 指数。在临床研究中，重点是了解 行为学、生理学和药理学的关系 变量。生化，生理学，神经内分泌学， 行为和心理测量技术被用来评估 急性和亚慢性给药的后果。 认识到人们很少将吸毒限制在一种药物上 或药物类别、开发和应用的研究 适用于多种药物研究的策略 而不是用特定的方法或药物进行专业化 阶级是一种指导思想。在可能的情况下，机制和 对药物效应个体差异的解释进行了研究。 自然发生与药物诱发的关系 精神障碍(例如，抑郁、焦虑状态和 精神分裂症或其他精神病)仍然是一个令人感兴趣的话题。这个 研究是多学科的，只涉及人类受试者。 应进一步认识人类精神活性药物 使用、其健康后果及其管理。

This is a request for continuation of a Research Scientist Award. My broadest objectives are to understand why people take psychoactive drugs, what are usual and expected effects, what might account for unexpected consequences, and how might adverse consequences best be managed. For example, how might tolerance and dependence determine individual differences in drug use and drug effects? Individual projects study the pharmacokinetics and pharmacodynamics of cocaine and methamphetamine administered by various routes, and their interactions with ethanol. The pharmacokinetics and cardiovascular, autonomic, EEG, neuroendocrine and subjective effects of substituted phenethylamines, 3,4-methylene- dioxymethamphetamine (MDMA) and related compounds will be compared to lysergic acid diethylamide (LSD), methamphetamine and cocaine. Modification of tolerance and dependence associated with cocaine and methamphetamine administration by new and novel treatment medications will be studied. The pharmacokinetics of deuterium-labeled cocaine, cocaethylene, morphine and methamphetamine in hair, skin, sweat, sebum and plasma will be- characterized to better understand mechanisms by which drugs enter hair and to judge the utility of analysis of hair and sweat as biomarkers of drug exposure. Characterization of the pharmacokinetics and dynamics of buprenorphine and its interactions with naloxone and factors altering such effects is studied as part of the evaluation of new pharmacologic treatments for opiate, cocaine and related dependence. As is possible, equal attention is given to psychological and behavioral measures, assessment of mood, neurophysiological and neurochemical indices. in the clinical studies, emphasis is on understanding relationships between behavioral, physiologic and pharmacologic variables. Biochemical, physiologic, neuroendocrinologic, behavioral and psychometric techniques are used to assess consequences of acute and subchronic drug administration. 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 rather than specialization with a particular methodology or drug class is a guiding philosophy. 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) remains a topic of interest. The studies are multidisciplinary and involve only human subjects. They should further understanding of human psychoactive drug use, its health consequences and its management.