A high dose of naloxone (30 mg/70 kg) did not reverse the pain-relieving effects of 30% nitrous oxide in a crossover trial with 14 subjects. Participants inhaled either 30% nitrous oxide or pure oxygen, then received intravenous naloxone or saline. Naloxone increased pain ratings overall and impaired mood and psychomotor performance, but it did not counteract nitrous oxide's analgesic or subjective effects. The findings question whether the opioid system mediates nitrous oxide's effects in humans.
Inhaling a brief, high-concentration bolus of nitrous oxide produces short-lived subjective effects including increased ratings of 'high,' 'tingling,' 'stimulated,' and 'confused,' along with greater euphoria and psychedelic-like effects, especially at 40% and 80% concentrations. These effects typically dissipated within minutes. Psychomotor performance measured 2.5 minutes after inhalation did not differ from baseline, though the timing of measurement may have missed peak effects. The findings align with the recreational appeal of nitrous oxide.