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

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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