INTRAVENOUS COCAINE ADMINISTRATION IN THE PRESENCE OF DISULFIRAM IN HUMANS: PHAR

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是进一步阐明同时使用可卡因和酒精的心理生理学，进一步了解可卡因在可卡因-酒精联合滥用的生物学、生理学和行为效应中的作用，并探索影响这两种物质滥用的治疗方案，特别是双硫仑作为治疗可卡因滥用和可卡因-酒精滥用的潜力。可卡因的滥用和依赖已成为一个最严重的公共卫生问题，国家药物滥用研究所已将其宣布为“国家公共卫生最关切的药物”。全国毒品开发协会估计，至少有200万人是可卡因成瘾者，有1至300万人需要治疗。最近已经确定，62-90%的可卡因滥用者同时也是酒精滥用者，同时消费是很常见的。拟议的在稳定的乙醇浓度下反复给药可卡因的研究将更接近这些物质的街头使用情况，也将开始解决有关可卡因和乙醇联合使用的行为和生理影响关系的重要问题。因为可卡因、乙醇和可卡因与毒性有关；在有乙醇存在的情况下反复服用可卡因是否会产生耐受性，这一问题对于理解可卡因/酒精使用的发病机制很重要。对可卡因和乙醇的行为影响有耐受性，但对心血管的影响没有伴随耐受性，这可能是这些药物滥用和相关毒性的基础。相当多的临床前神经化学和行为数据表明，可卡因可能与可卡因一样具有精神作用。最近报道了对可卡因的神经化学和行为影响的实验室研究。本研究的研究对象将通过广告招募，并且将是不寻求治疗的常规可卡因滥用者。在研究对象入组时，将对受试者的精神病学、行为学、生理和生化方面进行评估。受试者将作为住院病人接受可卡因、酒精、可卡因和双硫仑的治疗。所有的给药程序都将在持续的医疗监督下进行，有经验丰富的护理人员随时在场，并在专门设计、装备和运作以支持这些类型研究的设施中进行

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to further clarify the psychophysiology of simultaneous use of cocaine and alcohol, to further understand the role of cocaethylene in the biological, physiological, and behavioral effects of combined cocaine-alcohol abuse, and to explore treatment options which will impact the abuse of both substances, specifically the potential of disulfiram as a treatment for cocaine abuse and cocaine-alcohol abuse. Cocaine abuse and dependence has become a most serious public health problem having been proclaimed "the drug of greatest national public health concern" by the National Institute on Drug Abuse (NIDA). NIDA estimates that at least 2 million persons are cocaine addicts and that 1-3 million persons are in need of treatment . More recently it has been established that 62-90% of cocaine abusers are also concurrent alcohol abusers and that simultaneous consumption is common. The proposed study of repeated cocaine administration in the presence of steady state ethanol concentration will more closely approximate street use of these substances, and would also begin to address important questions regarding the relationship of behavioral and physiological effects of combined cocaine and ethanol use. Because of the association of cocaine, ethanol, and cocaethylene with toxicity; the question of whether tolerance will occur after repeated administration of cocaine in the presence of ethanol is important to understanding the pathogenesis of cocaine/alcohol use. Tolerance to the behavioral effects of cocaine and ethanol without concomitant tolerance to cardiovascular effects may underlie binge use of these drugs and associated toxicity. Considerable preclinical neurochemical and behavioral data suggest that cocaethylene is likely to have psychotropic effects in common with cocaine. Laboratory investigations of the neurochemical and behavioral effects of cocaethylene have recently been reported. Research subjects for this study will be recruited via advertising and will be regular cocaine abusers not seeking treatment. Psychiatric, behavioral, physiological and biochemical aspects of subjects will be assessed upon enrollment of research subjects. Subjects will be seen as inpatients for administration of cocaine, alcohol, cocaethylene and disulfiram. All of the drug administration procedures will be performed in the presence of constant medical supervision with experienced nursing staff always in attendance and in facilities specifically designed, equipped, and functioning in support of these types of studies