Time course of effects of brief inhalations of nitrous oxide in normal volunteers

Nitrous oxide is commonly used (abused) recreationally by inhaling it in a bolus form (i.e. single or several breaths). The time course of the psychoactive effects of nitrous oxide, via this mode of inhalation, has not been adequately characterized and thus formed the basis for this study. Twelve healthy volunteers participated in four sessions, using a randomized, cross-over, placebo-controlled design. In each session one of the following four measures were assessed: self-reported strength of drug effects, mood, memory and psychomotor performance. Within sessions, subjects were exposed to four different concentrations of nitrous oxide in a randomized fashion: 0% (oxygen-placebo), 40%, 60% and 80%. At each concentration, or "trial", subjects took four deep breaths of the gas. Peak drug effects, as reported by our subjects, occurred within 30 seconds after the last inhalation of nitrous oxide, persisted for about a minute, and then gradually subsided to near-baseline levels by 5 minutes post-inhalation. Certain aspects of mood were briefly affected by nitrous oxide, generally in a dose-related fashion with increases in visual analog scale ratings of "anxious", "stimulated", "coasting (spaced out)", "lightheaded", "confused", and "high". Free recall of wards that had been presented between 30 and 60 seconds post-inhalation was significantly reduced after 80% nitrous oxide, relative to oxygen-placebo. There was a trend towards psychomotor impairment (Concentration x time: p = 0.08), as measured by the Digit Symbol Substitution Test, with peak decrements in performance (about a minute after inhalation) being greater after 80% nitrous oxide than after 0% nitrous oxide. Our results suggest that there arc acute, albeit brief, adverse effects of inhaling bolus concentrations of nitrous oxide.