Within-subject comparison of the subjective and psychomotor effects of a gaseous anesthetic and two volatile anesthetics in healthy volunteers.

Inhalant abuse is a serious public health problem throughout the world. The present study compared the states of intoxication produced by three inhaled anesthetics that represent two of the three major classes of abused inhalants, as classified by [Balster, R.L., 1998. Neural basis of inhalant abuse. Drug Alcohol Depend 51, 207-214.]. Isoflurane and sevoflurane represent the class of volatile substances, and nitrous oxide (N2O) comprises a class of its own. Fourteen healthy volunteers inhaled the vehicle (100% O2) and two concentrations each of isoflurane (0.1 and 0.2%), sevoflurane (0.2 and 0.4%), and N2O (15 and 30%) for 40 min each, across seven separate sessions. Drug concentrations were chosen to produce similar ratings of drug effect strength and similar impairment on a psychomotor test, the digit-symbol substitution test (DSST). Ratings of drug effect strength and performance on the DSST were similar across drugs; however, the volatile anesthetics produced greater sedation and greater impairment on three other psychomotor tests than N2O, whereas N2O produced a greater magnitude of putatively pleasant and psychedelic-like subjective effects. These results are consistent with the drugs' putative receptor mechanisms of action and confirm Balster's classification of the volatile anesthetics into a class distinct from N2O.

Reinforcing and subjective effects of the volatile anesthetic, sevoflurane.

Sevoflurane is a volatile anesthetic that is chemically similar to volatile substances of abuse and can be safely administered to humans in laboratory research. In this study, the reinforcing and subjective effects of five concentrations of sevoflurane (0, 0.2, 0.4, 0.6, 0.8% sevoflurane in O2) were studied in 20 non-drug-abusers. During each of five sessions, subjects sampled a concentration of sevoflurane and 100% O2 (placebo) for 10 min each. Later, within the session, they chose nine times, once every 5 min, among sevoflurane (e.g. "Agent A"), placebo (e.g. "Agent B"), or neither (and were administered 100% O2, identified as "drug-free air"). Although "neither" was selected most frequently, mean preference ratios (sevoflurane choices/[sevoflurane choices+placebo choices]) and total sevoflurane choice peaked at the 0.4% concentration. Choice patterns varied across subjects, with some subjects never choosing sevoflurane and other subjects showing monotonic increasing or bitonic concentration-choice functions. Concentration-related increases in subjective effects were observed, including effects that are putatively associated with abuse liability. Ratings of drug liking and of wanting to inhale the drug again were positively correlated with sevoflurane choice. This study shows that sevoflurane can function as a reinforcer and produce abuse liability-related subjective effects in some healthy volunteers.

The effects of a cold-water stimulus on butorphanol effects in males and females.

Using a crossover, randomized, double-blind, cumulative-dosing procedure, we examined whether a painful stimulus modulated subjective and psychomotor effects of butorphanol in eight male and eight female volunteers. During each session, volunteers received four intravenous injections of either butorphanol (0, 0.5, 1, and 2 mg/70 kg) or saline (placebo) at hourly intervals. Saline and butorphanol were tested in two conditions, forearm immersion 30 min after each injection into either 2 or 37 degrees C water. During the 180-s immersion, volunteers completed a visual analog scale (VAS), psychomotor test, and pain ratings. VAS ratings of "Coasting ('spaced out')", "heavy or sluggish feeling," and "sleepy" were lower in the 2 degrees C than in the 37 degrees C condition during butorphanol administration, but only in females. Modulation by a painful stimulus of sleepy ratings was confined to the third immersion (i.e., a dose effect). The cold-water stimulus significantly decreased butorphanol-induced impairment during the third immersion for males, and females showed a similar trend. Overall, pain ratings were higher in females, and although not significant, males reported a greater degree of analgesia. The differences in pain ratings and degree of analgesia between the sexes are discussed as a possible mechanism for the sex differences in modulatory effects.