Placebo-effects contribute to differences in the acquisition of drug discrimination by humans: a retrospective analysis.

Adult human volunteers (n = 50) were trained to discriminate triazolam (TRZ, 0.32mg/70kg, p.o.) from placebo. Based on a criterion that required greater than 80% capsule-appropriate responding during each of four test sessions, 19 subjects were designated non-discriminators (NDs) and 31 were designated discriminators (Ds). NDs and Ds did not differ significantly in age, weight, gender or previous drug use and generally reported similar effects following TRZ. NDs reported greater effects following placebo than Ds on several measures, including 'good', 'bad', 'high' and sedative drug effects, suggesting that NDs in this study were 'placebo reactors'. These results show that NDs and Ds of TRZ differed in self-reported responses and suggest a close relationship between acquisition of a drug discrimination and self-reported effects of drugs. Moreover, greater placebo effects may hinder acquisition of TRZ discrimination.

Acute behavioral effects of lorazepam and caffeine, alone and in combination, in humans.

The widespread use of benzodiazepines and caffeine makes their combined use inevitable. The purpose of the present experiment was to assess the acute effects of lorazepam (0,2.8 and 5.6mg/70kg) and caffeine (0, 250 and 500mg/70kg), alone and in combination, on human learning, performance and self-reports. Subjects were nine healthy, male volunteers. Subjects received all possible combinations according to a Latin Square design. Lorazepam administered alone dose-dependently disrupted learning and performance on the Repeated Acquisition and Performance procedure and Digit Symbol Substitution Test (DSST), and increased subject ratings of sedation. Caffeine administered alone did not affect learning, performance or subject ratings to a statistically significant degree. Caffeine attenuated lorazepam-induced decrements in learning and performance on the Repeated Acquisition and Performance procedure and DSST. Consistent with the learning and performance measures, caffeine offset lorazepam-induced increases in subject ratings of sedation. These results demonstrate that caffeine generally attenuates the behavioral and self-reported effects of lorazepam on a variety of performance measures. An important extension of these findings would be to test the combined effects of lorazepam and caffeine in other behavioral paradigms such as drug self-administration.