TITLE: VARIABILITY OF NITROUS OXIDE EFFECTS IN HUMANS ACROSS MULTIPLE EXPOSURES TO THE DRUG

AUTHORS: Diana J. Walker, PhD, Veronica M. Camarillo, BA, James P. Zacny, PhD
AFFILIATION: The University of Chicago, Chicago, IL.

INTRODUCTION: The phenomena of sensitization and tolerance following chronic (e.g., daily) exposure to drugs have been studied extensively; however, relatively few studies have examined the extent of variability in drug effects after repeated (e.g., weekly), but not chronic administration. The purpose of this study was to determine whether people react differently to nitrous oxide (N₂O) on different occasions or whether drug effects are similar across repeated, non-daily exposures to the drug.
METHODS: Twelve healthy volunteers attended five sessions, separated by at least three days. The sessions were virtually identical in procedure (e.g., same protocol, same time of day). Subjects were exposed to 30% N₂O (in O₂) and to 100% O₂ and were asked to rate their mood and to complete a psychomotor test, the Digit Symbol Substitution Test. Later they could choose which option to inhale (N₂O or O₂), such that rewarding, or reinforcing, effects of the drug were tested.
RESULTS: None of the observed drug effects varied syste- matically as a function of session number; that is, no tolerance or sensitization was detected. The extent of between-subject variability was generally greater than the extent of within-subject variability, indicating individual differences in N₂O effects but relatively similar responses to the drug from the same individual. Although some mood effects (e.g., ratings of "high" and "tingling") did fluctuate for some subjects, ratings of the strength of drug effect and psychomotor performance, as well as rewarding effects (number of choices of N₂O over O₂) were remarkably consistent across sessions for all subjects.
DISCUSSION: These results suggest that responses to inhaled anesthetics will be similar to those that were experienced during initial exposure to the drug.