Moderate drinkers chose to inhale nitrous oxide significantly more often than placebo and more often than light drinkers did. At 20% and 30% concentrations, moderate drinkers also reported stronger abuse-liability-related subjective effects. The findings provide more conclusive evidence that alcohol-drinking status modulates both the choice and subjective effects of nitrous oxide.
Inhalant abuse is a global health problem. This study compared intoxication from three inhaled anesthetics: isoflurane, sevoflurane (volatile substances), and nitrous oxide (N2O). Fourteen healthy volunteers inhaled vehicle (100% O2) and two concentrations of each drug for 40 minutes across seven sessions. Drug concentrations were chosen to produce similar ratings of drug effect strength and similar impairment on a psychomotor test. While ratings of drug effect strength and performance on that test were similar across drugs, volatile anesthetics caused greater sedation and more impairment on three other psychomotor tests than N2O, whereas N2O produced more pleasant and psychedelic-like subjective effects. These results align with the drugs' receptor mechanisms and support classifying volatile anesthetics separately from N2O.
In 20 non-drug-abusers, nitrous oxide (laughing gas) acted as a reinforcer—meaning participants chose to take it again—at doses of 10, 20, 30, and 40% in oxygen, compared to placebo (100% oxygen). Preference for nitrous oxide increased with dose, and at least one active dose functioned as a reinforcer in 80% of subjects, though the effective dose varied across individuals. Choice of nitrous oxide was linked to later ratings of liking and wanting to inhale it again, but not to ratings taken while under the drug's influence. Placebo was chosen less often than a no-drug option, even though both were 100% oxygen. Including a no-drug option made preference ratios easier to interpret than in forced-choice procedures.