A dose-response study of the effects of inhaled nitrous oxide on psychological performance and mood

In this five-period randomised double-blind crossover study, 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0% (placebo); 5%, 10%; 20% and 40% in oxygen. Each concentration was inhaled for about 1 h, each period being on a separate day. The effects of nitrous oxide were measured using a comprehensive battery of performance tests including measures of attention, psychomotor function, memory and cognition. Mood was assessed with visual analogue scales. All tests except critical flicker fusion showed substantial effects at the highest does (40%). No measure showed evidence of change at the lowest concentration (5%). Several measures showed significant impairment at 10%, viz: digit-symbol substitution, choice reaction time (latency and total), tapping, and continuous attention. Subjects felt dizzy and muzzy on nitrous oxide, but no significant effect was seen on the Alert-Drowsy VAS. The dose-response profiles of the various tests showed substantial differences. Thus tapping was virtually linear, while choice reaction motor time and body sway showed steeply accelerating impairment with increasing dose. These results indicate that comparisons of profiles of drug-induced change must take into account the variable effects of dose before interpretations in terms of specific drug effects can be made.