Drug preference in humans: double-blind choice comparison of pentobarbital, diazepam and placebo

In a residential hospital research ward setting the effects of and preference for placebo and various oral doses of pentobarbital and diazepam were studied in volunteer human subjects with documented histories of sedative abuse. Drug-free days alternated with drug administration days throughout the study. After experimenter-scheduled exposures to the test drugs, subjects were given repeated opportunities to choose between two available drug alternatives. In experiment 1, pentobarbital (200-900 mg) produced dose-related increases in subject- and observer-rated drug effects, and subjects generally chose higher pentobarbital doses over lower doses. In experiment 2, diazepam (50-400 mg) produced only modest elevations in drug effect ratings and subjects did not consistently choose higher doses over lower doses. In experiment 3, 400 mg of pentobarbital and 200 mg of diazepam produced subject and observer drug effect ratings of similar magnitude while placebo produced negligible effects. All subjects chose pentobarbital over placebo and diazepam over placebo on all occasions; all subjects chose pentobarbital over diazepam on the majority of choice trials. Clinical impression confirmed by a post hoc analysis of nursing notes indicated that diazepam produced relatively subtle yet reliable changes in the global mood and behavior of the subjects in the direction of increased complaining, dysphoria and disruptivenes. The finding that pentobarbital is preferred to diazepam is compatible with previous human and animal drug self-administration studies as well as clinical information about the abuse of these drugs.