Midazolam 12 mg is moderately counteracted by 250 mg caffeine in man

Objective: Caffeine (Caf) counteracts various effects of benzodiazepines (B ZDs). Since the effects of zolpidem, a short-acting atypical GABAA-BZD agon ist, were not antagonized by Caf, we studied am interaction between Caf;and midazolam (Mid) in healthy volunteers. Subjects, materials and methods: In Study 1, 108 healthy students divided to 6 parallel groups were given Mid 12 mg (capsule) and Caf 125 and 250 mg (in decaffeinated coffee), alone and in combinations in the double-blind placebo-controlled manner. Objective a nd subjective tests were done before and at 45 and 90 min after intake. Ran ked Delta -values (changes from base:line) were analyzed by one-way contras t ANOVA and Scheffe's tests. In Study 2, six healthy subjects took Mid 15 m g (tablet) with and without Caf 300 mg. The dynamic effects were analyzed a s in Study 1 and the plasma concentrations were assayed. Results: Study 1, learn effects after placebo (ad +15%) were seen for letter cancellation and digit symbol substitution tests. Midazolam alone significantly (p < 0.05 v s. <Delta>-placebo) reduced letter cancellation and digit symbol substituti on, lowered flicker fusion, impaired digit learning and caused subjective c almness on VAS. Caffeine alone did not differ from placebo objectively, yet improved quick-wittedness and contentedness on VAS. In the combinations, M id+Caf 125 mg differed from placebo objectively as Mid alone, whereas Mid Caf 250 mg did not. Mid + Caf 250 mg differed from Mid on digit substituti on, but did not differ from Mid+Caf 150 mg in impairing memory and causing subjective sedation. In Study 2, Mid 15 mg caused sedation and Caf300 mg in creased plasma Mid at 45 min. Mid + Caf did not differ from Mid alone objec tively, but did so subjectively on VAS (p > 0.05). Conclusion: In conclusio n, in a parallel group study, sedative effects of Mid 12 mg were only moder ately antagonized by Caf 250 mg but not by Caf 125 mg. In a crossover study , a weak interaction was found subjectively but not in objective measures.