Subjective and psychomotor effects of nitrous oxide in healthy volunteers.

In 12 healthy volunteers, inhaling 20% and 40% nitrous oxide produced robust mood changes, including confusion, sedation, euphoria, dysphoria, and stimulation during inhalation, with fatigue, depression, and anxiety increasing after 40% nitrous oxide stopped. Performance on the Digit Symbol Substitution Test was significantly impaired during 40% nitrous oxide but recovered quickly. Sex differences in subjective effects emerged. Eight of 12 subjects liked the 40% concentration, one was neutral, and three disliked it. Peak effect ratings were dose-related.

Study at a glance

Abstract

The effects of nitrous oxide at subanesthetic doses (0%, 10%, 20%, and 40% in oxygen) on mood and psychomotor performance were determined in a group of 12 healthy volunteers (six males and six females). A randomized, placebo-controlled, double-blinded, crossover trial of five experimental sessions was used. Effects were measured before, during and after a 30-min inhalation period of the agent, using three subjective effects questionnaires (the Profile of Mood States, the Addiction Research Center Inventory, and the Visual Analogue Scale); and two psychomotor tests (auditory reaction time and Digit Symbol Substitution Test). In addition, an End-of-Session questionnaire, administered 60min after cessation of inhaling the agent, was used, which measured the subjects' reactions to the agent inhaled that day (i.e. peak concentration effect and concentration liking). The primary effects observed from nitrous oxide were confined to the inhalation of 20% and 40% concentrations. Subjects became more confused, sedated, high, dysphoric, and stimulated during inhalation of 40% nitrous oxide; fatigue, depression and anxiety increased after inhalation of 40% nitrous oxide had ceased. Significant or near-significant differences on several measures of subjective effects emerged between sexes. On the End-of-Session questionnaire, subjects' ratings of the peak effect of nitrous oxide were dose-related. There was individual variation in the degree to which subjects liked nitrous oxide: eight of the 12 subjects reported liking the 40% concentration, one was neutral, and three did not like it. Subjects' performance on the DSST was significantly impaired during inhalation of 40% nitrous oxide, but recovered soon after inhalation stopped. In summary, nitrous oxide had robust effects on mood, there appeared to be sex differences in the magnitude of subjective effects of nitrous oxide, and there was some variability in the extent to which subjects liked the anesthetic agent.