Analysis of the reinforcing and subjective effects of different doses of nitrous oxide using a free-choice procedure.

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.

Study at a glance

Abstract

The reinforcing and subjective effects of five doses of nitrous oxide (0, 10, 20, 30, 40% N(2)O in O(2)) were studied in 20 non-drug-abusers using a free-choice procedure. During each of five sessions, subjects sampled a dose of N(2)O and 100% O(2) (placebo) for 10 min each. Later they chose nine times, once every 5 min, among N(2)O (e.g. 'Agent A'), placebo (e.g. 'Agent B'), or a no-drug option. Mean preference ratios (N(2)O choices/[N(2)O choices+placebo choices]) and total N(2)O choice increased with increasing N(2)O dose. Individual preference ratios suggested that at least one active dose of N(2)O functioned as a reinforcer in 80% of subjects, and the doses that functioned as reinforcers varied across subjects. N(2)O choice was positively correlated with end-of-session and post-session ratings of N(2)O liking and of wanting to inhale N(2)O again, but not with ratings of those effects during sampling. Placebo was chosen significantly less than the no-drug option, even though both were 100% O(2). More robust reinforcing effects of N(2)O were observed in this subject population than in previous studies. Choice data emphasize the importance of examining a range of doses, and of examining those effects within-subject, when assessing reinforcing effects of drugs. Inclusion of the no-drug option eliminated the 'forced' choice of placebo, making preference ratios easier to interpret than in previous, forced-choice procedures. Reinforcing effects were more correlated with subjective effects assessed after the session than with subjective effects obtained while subjects were under the influence of the drug.