Cocaine use has become an increasing concern over the past several years. More recently, cocaine use via the smoking route has gained prominence. The use of cocaine via this route have increased form 1% in 1977 to 18% in 1984. In spite of the dramatic increase, there have been very few studies which have examined the effects of cocaine via this route either in animals or humans. Furthermore, there has been little systematic research on factors which may affect or maintain self-administration of cocaine in humans. The goals of the proposed studies are to establish basic experimental procedures and to provide an understanding of the patterns and effects of cocaine use via several routes of administration as well as factors which affect its use. The unique characteristics of this grant proposal are: (1) the availability of a device to administer a controlled dose of smoked cocaine base and (2) the parallel studies which will be conducted in humans and monkeys. Human subjects will be housed in the General Clinical Research Center. The specific objective of the first study will be to compare the bioavailability, and the subjective and physical effects of smoked cocaine with that of intravenously and intranasally administered cocaine. Subjects will be randomly administered three dosed of cocaine and placebo across all three routes of administration. The goal of the second study is to examine the patter of self-administration of cocaine and to determine factors which initiate and maintain the use of cocaine (e.g., dose, plasma cocaine levels, subjective states, physiological states). Subjects will be given three doses of cocaine and placebo in repeated and randomized trials. The goal of the third study is to provide a quantitative measure of the effect of dietary factors on the self-administration of cocaine. Cocaine self-administration will be carefully monitored while their daily caloric intake is increased or decreased. The goal of the fourth study is to determine withdrawal signs and symptoms from cocaine abstinence. Measures will be taken during cocaine self-administration and subsequent removal of the drug. The results from these studies will lead to future animal and human studies which will examine other factors contributing to decreases in cocaine self- administration, withdrawal effects, and relapse to drug use.
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