Repeated administration of diazepam and triazolam to subjects with histories of drug abuse

The present study examined the effects of repeated administration of diazepam (DZ) and triazolam (TZ) on psychomotor performance and subject-rated drug liking. Subjects were 11 males (30-41 years) who had documented histories of drug abuse and who resided on a behavioral pharmacology research ward. Six subjects received 80 mg DZ every third day (3 subjects) or every sixth day (3 subjects) for a total of 3-6 dosing occasions and six subjects received TZ (2.0 or 3.0 mg) every second day (4 subjects) or every third day (2 subjects) for a total of 3-5 dosing occasions. The results showed that on the first dose occasion, the two drugs produced generally similar degrees of psychomotor impairment and subject-rated drug liking. Following the first DZ dose, subsequent doses produced less of an effect (i.e. single-dose tolerance). Across at least the first three dose occasions, progressive tolerance development was observed with DZ but no tolerance was observed with TZ. It is hypothesized that pharmacokinetic differences between DZ and TZ may account for the difference in the development of tolerance.