Buspirone and lorazepam abuse liability in humans: behavioral effects, subjective effects and choice

This study compared behavioral and subjective effects of two anxiolytics, the benzodiazepine lorazepam and the azaspirodecanedione buspirone, in healthy male volunteers with histories of sedative drug abuse. Placebo, lorazepam (1, 2, 4, 8 mg/70 kg) and buspirone (15, 30, 60, 120 mg/70 kg) were administered p.o. in a mixed sequence in a double-blind, cross-over design. Lorazepam, but not buspirone, decreased psychomotor/cognitive performance. Both drugs produced similar increases in ratings of drug strength, however the onset and offset times for lorazepam were later than for buspirone. Lorazepam increased ratings of liking in contrast to buspirone which produced negative mood-related subjective effects (e.g. increases in ratings of disliking, bad/unpleasant effects, and tension-anxiety). Lorazepam was categorized by subjects as producing effects similar to barbiturates or benzodiazepines in contrast to buspirone which was not. When subjects were given a choice between self-administering an intermediate dose of lorazepam (4 mg/70 kg) or buspirone (60 mg/70 kg), which produced similar ratings of drug strength, eight out of nine subjects chose lorazepam. This study provides the clearest human experimental evidence to date that the abuse liability of buspirone is lower than that of a prototypic benzodiazepine, even at supratherapeutic doses.