Research will be conducted with human volunteers to examine the reinforcing, behavioral, and subjective effects of benzodiazepines and anorectic stimulants. Five interrelated sets of experiments on benzodiazepines will be undertaken on a residential research ward with volunteers with histories of drug abuse. One set of experiments will explore differences in reinforcing properties and abuse liability by systematically comparing compounds to interest. The second set of studies will characterize the interactive effects between diazepam and methadone. Another set of experiments will examine the effects of a benzodiazepine receptor antagonist alone, and in combination with several psychoactive drugs including diazepam. The fourth set of studies will characterize benzodiazepine interactions with caffeine administration and coffee drinking. The final set of studies will be undertaken to develop and refine a variety of behavioral measures which may be sensitive to benzodiazepines. Concurrent with conducting these experiments on the residential unit, a series of studies will be undertaken to examine the reinforcing, behavioral, and subjective effects of anorectic stimulant drugs in the context of a therapeutic outpatient treatment program for overweight. As a whole, the experiments will provide information about the relative abuse liability of benzodiazepines and anorectic stimulants. In addition, studies of benzodiazepines will provide information about the basic pharmacological and molecular mechanisms of action of these widely used therapeutic agents. More generally, this research project will contribute to an improved understanding of benzodiazepine and anorectic stimulant drug abuse, and will ultimately contribute to the development of improved prevention, control, and treatment procedures.
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