NEUROPSYCHOPHARMACOLOGY OF ALTERED CONSCIOUSNESS

这是一个研究科学家奖延续的请求。 我最广泛的目标是了解为什么人们 精神活性药物，通常和预期的影响是什么，什么 可以解释意想不到的后果，以及如何可能 最好能控制不良后果。例如，如何 耐受性和依赖性决定了药物的个体差异 使用和药物影响？个别项目研究 可卡因的药代动力学和药效学， 通过各种途径施用的甲基苯丙胺， 与乙醇的相互作用的药代动力学和 心血管、自主神经、EEG、神经内分泌和主观 取代的苯乙胺，3，4-亚甲基- 二氧甲基苯丙胺（MDMA）和相关化合物将被 与麦角酰二乙胺（LSD）、甲基苯丙胺相比， 还有可卡因相关耐受性和依赖性的改变 可卡因和甲基苯丙胺的管理， 将研究新的治疗药物。药代动力学 氘标记的可卡因可卡因吗啡 头发、皮肤、汗液、皮脂和血浆中的甲基苯丙胺会- 更好地理解药物 输入头发和判断头发和汗液分析的效用， 药物暴露的生物标志物。表征 丁丙诺啡的药代动力学和动力学及其 与纳洛酮的相互作用和改变这种作用的因素， 作为新药物治疗评估的一部分进行研究 鸦片、可卡因和相关的依赖。尽可能的，平等的 注意心理和行为措施， 情绪、神经生理和神经化学评估 指数。在临床研究中，重点是了解 行为、生理和药理学之间的关系 变量生化、生理、神经内分泌， 行为和心理测量技术用于评估 急性和亚慢性给药的后果。 认识到人们很少限制服用单一药物 或药物类别，研究开发和应用 适用于研究多类药物的策略 而不是专门研究特定的方法或药物 阶级是一种指导哲学。在可能的情况下， 研究了药物作用的个体差异的解释。 自然发生与药物诱导的关系 疾病（例如，抑郁症，焦虑状态和 精神分裂症或其他精神病）仍然是感兴趣的主题。的 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.