Addiction (Abingdon, England)
December 1, 2001
D J Walker, J P Zacny
Neither a history of light or moderate alcohol use nor acute doses of ethanol (0.35 or 0.7 g/kg) altered the abuse liability of 30% nitrous oxide in healthy light and moderate drinkers. Choice of nitrous oxide was similar across groups and ethanol doses, averaging about 3.3 out of 6 choices. Subjective effects like liking and desire to inhale the drug again were positively correlated with choice, but these effects were also unaffected by ethanol history or pretreatment. The findings suggest that, under these experimental conditions, ethanol does not modulate the reinforcing or subjective effects of nitrous oxide.
Drug and alcohol dependence
September 1, 2001
D J Walker, J P Zacny
The reinforcing and subjective effects of nitrous oxide varied more between people than within the same person across sessions. Twelve volunteers without drug dependence inhaled 30% nitrous oxide or 100% oxygen for 10 minutes each, then chose between the two or drug-free air nine times per session. Choice differed across subjects but stayed stable within subjects. Some subjective effects correlated with choice and differed between consistent choosers of nitrous oxide and non-choosers, but drug liking and euphoria—standard measures of abuse liability—were unrelated to choice. Subjective effects fluctuated across sessions more than reinforcing effects did, underscoring the need for multiple measures when assessing abuse liability.
Addiction (Abingdon, England)
December 1, 1999
J P Zacny, D Janiszewski, P Sadeghi et al.
Sevoflurane, a volatile anesthetic, was tested at subanesthetic concentrations (0.2, 0.4, 0.6%) against placebo and 30% nitrous oxide in moderate-drinking volunteers. Neither drug was chosen significantly more often than chance: nitrous oxide was chosen by 71% of subjects, and sevoflurane by 50%, 57%, and 50% at the three concentrations. Both drugs impaired psychomotor performance and altered mood, with some differences in subjective effects. Although sevoflurane did not act as a reinforcer for most participants, those who chose it reported more positive subjective effects during sampling, suggesting it can function as a reinforcer in some individuals.
Drug and alcohol dependence
October 1, 1998
J P Zacny, V M Camarillo, P Sadeghi et al.
Recreational users sometimes combine ethanol and nitrous oxide (N2O), but their combined subjective effects were unstudied. In 11 volunteers, ethanol (0, 0.25, or 0.5 g/kg) was consumed, followed 15 minutes later by inhaling 30% N2O or placebo oxygen for 35 minutes. Thirty minutes into inhalation, subjects immersed a forearm in icy water for 3 minutes. Ethanol increased ratings of feeling drug effect and drunkenness. N2O altered mood, impaired cognitive and psychomotor performance, and reduced pain reports. Ethanol potentiated some N2O effects, and the combination produced effects neither drug alone did, but ethanol did not enhance N2O's analgesic effects. The data did not convincingly show the combination had greater abuse liability than N2O alone at the tested doses.
Drug and alcohol dependence
November 25, 1997
J P Zacny, A M Cho, A Y Toledano et al.
Being told what drug and effects to expect can change how people respond to nitrous oxide. Healthy volunteers could choose between inhaling nitrous oxide (10-40% concentration) or placebo (oxygen) after sampling both. One group was told the concentration and typical effects (tingling, euphoria, dysphoria); the other was only told the drug came from one of six classes. Thirty percent nitrous oxide was chosen more often than chance only by informed participants, and the probability of choosing 20-40% nitrous oxide was higher in the informed group. Subjective effects were unaffected, but psychomotor impairment at the highest concentration was greater in the non-informed group, suggesting that information can modulate reinforcing and impairing effects.
Anesthesiology
November 1, 1997
J L Galinkin, D Janiszewski, C J Young et al.
Sevoflurane, a volatile general anesthetic, and nitrous oxide, a gaseous anesthetic, produce different subjective, psychomotor, and analgesic effects at equal subanesthetic concentrations. In 12 healthy volunteers, sevoflurane caused greater amnesia, psychomotor impairment, and drowsiness than nitrous oxide, while only nitrous oxide provided analgesic effects. Recovery from both drugs was rapid. The distinct effect profiles align with their chemical and mechanistic differences.
Drug and alcohol dependence
April 14, 1997
A M Cho, D W Coalson, P A Klock et al.
Moderate drinkers chose nitrous oxide more often than light drinkers in a laboratory choice procedure, suggesting that alcohol history may influence the reinforcing effects of the drug. Healthy volunteers sampled placebo and 10-40% nitrous oxide across four sessions and then chose between the two. Most subjective and psychomotor-impairing effects did not differ between the groups. However, moderate drinkers selected nitrous oxide a median of three times, compared with one time for light drinkers, a statistically significant difference. The findings provide suggestive evidence that prior alcohol exposure modulates how rewarding nitrous oxide is.
Drug and alcohol dependence
November 1, 1996
J P Zacny, J M Klafta, D W Coalson et al.
Brief exposures (about 1.5 minutes) to nitrous oxide at concentrations of 20-80% in oxygen did not function as reinforcers in 11 healthy volunteers with modest lifetime psychoactive drug use. In a choice procedure, subjects sampled each concentration and placebo oxygen, then chose between them. 20%, 40%, 60%, and 80% nitrous oxide were chosen by five, four, three, and three subjects respectively, none exceeding chance levels. All concentrations produced psychoactive effects, with concentration-related subjective effects. The authors conclude that nitrous oxide inhaled in a manner similar to recreational use does not act as a reinforcer across a wide range of concentrations in this population.
Pharmacology, biochemistry, and behavior
June 1, 1996
S Yajnik, J P Zacny, C J Young et al.
A crossover, double-blind trial with eleven healthy volunteers tested whether acute drug tolerance develops to the subjective, cognitive, and psychomotor effects of subanesthetic nitrous oxide at doses of 0, 10, 20, 30, and 40%. Over a 120-minute inhalation period, there was little evidence of acute tolerance to the subjective or impairing effects at any concentration.
Neuroscience letters
May 10, 1996
J P Zacny, A M Cho, D W Coalson et al.
Inhaling nitrous oxide at increasing doses (10–40%) reduces pain intensity and the bother of pain from cold-water immersion, but this analgesic effect weakens over a 120-minute inhalation period (acute tolerance). Some pleasant subjective effects, such as elation and drug liking, also show acute tolerance. Other subjective effects and psychomotor impairment do not change significantly during the inhalation period, indicating no acute tolerance for those measures. The differing patterns of tolerance suggest that distinct neurochemical systems may mediate different effects of nitrous oxide.
Pharmacology, biochemistry, and behavior
August 1, 1995
J P Zacny, S Yajnik, D Coalson et al.
In two double-blind, randomized, crossover trials, eight healthy volunteers inhaled 30% nitrous oxide in oxygen for 35 minutes and were given flumazenil 10 minutes into the inhalation. Experiment 1 tested clinical doses of flumazenil (0, 0.25, 0.5, and 1.0 mg/70 kg), while Experiment 2 tested a supraclinical dose (0 and 5.0 mg/70 kg). Nitrous oxide increased ratings of high, drunk, and tingling and impaired psychomotor performance. Only the supraclinical flumazenil dose significantly reduced the high rating; other subjective effects showed non-significant decreases. Flumazenil did not affect nitrous oxide's psychomotor effects. The findings suggest that a high flumazenil dose may partially antagonize some subjective effects of nitrous oxide.
Drug and alcohol dependence
December 1, 1994
S Yajnik, P Thapar, J L Lichtor et al.
An experiment compared marijuana users and non-users to see if their history with cannabis affected how they responded to nitrous oxide. Participants first sampled both 40% nitrous oxide in oxygen and a placebo (100% oxygen), then chose which to inhale in later sessions. Both groups chose nitrous oxide less than half the time, and the choice patterns did not differ significantly between marijuana users and non-users. However, marijuana users reported stronger subjective effects from nitrous oxide, suggesting a history of marijuana use may intensify some of the drug's subjective experiences.
Pharmacology, biochemistry, and behavior
November 1, 1994
J P Zacny, D W Coalson, J L Lichtor et al.
Two double-blind, randomized experiments tested whether the opioid antagonist naloxone alters the mood-altering and performance-impairing effects of nitrous oxide. In both experiments, inhaling 30% nitrous oxide increased self-reported feelings of drug effect, carefreeness, drunkenness, sedation, and being high, and it worsened psychomotor performance. Naloxone, given intravenously at doses ranging from 0.01 to 10 mg per 70 kg, had no effects on its own and did not significantly change any of nitrous oxide's effects. The authors conclude that naloxone, at doses up to 10 mg, does not appear to influence the subjective or psychomotor effects of nitrous oxide.
Psychopharmacology
April 1, 1994
J P Zacny, G Sparacino, P Hoffmann et al.
In nine healthy volunteers, isoflurane and nitrous oxide produced similar subjective effects like feeling drunk and spaced out, but isoflurane uniquely increased confusion, sedation, and carefreeness while reducing perceived control over thoughts and body; it also had an unpleasant odor. Psychomotor performance was more impaired by isoflurane than by nitrous oxide, but recovery from both was rapid and complete within five minutes. Both drugs impaired immediate and delayed free recall. The findings suggest isoflurane may be less suitable than nitrous oxide for conscious sedation due to its greater psychomotor effects and unpleasant odor.
Drug and alcohol dependence
February 1, 1993
C S Dohrn, J L Lichtor, D W Coalson et al.
In healthy volunteers, inhaling 30% nitrous oxide was chosen no more often than oxygen (41.6% choice rate), showing it was not more reinforcing. Inhaling 40% nitrous oxide was chosen significantly less often than oxygen (22% choice rate), indicating it was less reinforcing. Nitrous oxide produced robust subjective effects such as increased ratings of 'high,' 'tingling,' and 'dizzy.' Subjects who chose nitrous oxide reported pleasant effects and liked it, while those who chose placebo reported unpleasant effects and disliked it. Both concentrations impaired psychomotor performance in all subjects. The lack of reinforcing effects is discussed in light of nitrous oxide's known abuse potential.