Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report

Two double-blind, randomized, crossover trials were conducted to study whether the benzodiazepine antagonist, flumazenil, would interact with the subjective and psychomotor effects of nitrous oxide in healthy volunteers. In both experiments, eight subjects inhaled 30% nitrous oxide in oxygen for 35 min and were challenged, 10 min into the inhalation, with flumazenil. Experiment 1 tested a range of flumazenil doses used clinically (0, 0.25, 0.5, and 1.0 mg/70 kg) whereas Experiment 2 tested a supraclinical flumazenil dose (0 and 5.0 mg/70 kg). Nitrous oxide increased mood ratings of "high," "drunk," and "tingling," and decreased psychomotor performance as assessed by the Digit Substitution Test. Flumazenil, at the supraclinical dose, significantly lowered the mood rating of "high." Decreases, though not significant (p < 0.10), were also obtained on the ratings "drunk," "elated," and "drug liking". Flumazenil, in both experiments, did not interact with the psychomotor effects of nitrous oxide. It appears that flumazenil, at a dose higher than that used clinically, may antagonize some of the subjective effects produced by nitrous oxide in humans.