Drug and alcohol dependence
May 1, 2026
Juan Carlos C Montoy, Ralph C Wang, Allison R Coker et al.
From 2002 to 2019, first-time use of any hallucinogen among US civilians aged 12 and older averaged 0.71% per year, with a small but statistically significant increase (odds ratio 1.009 per year). New use decreased among 12- to 17-year-olds (OR 0.96) and increased among those 65 and older (OR 1.56). LSD showed a notable rise (OR 1.08 per year), while psilocybin and MDMA did not. From 2021 to 2023, 0.79% reported new hallucinogen use, with no overall change (OR 0.97). Patterns of first-time use vary by substance and age group, with adolescents using less and older adults using more.
Drug and alcohol dependence
July 1, 2025
Dilara Bahceci, Krista Siefried, Maureen Steele et al.
Among 268 people who used methamphetamine, nearly half had a diagnosed mental illness and were at risk of suicide, and most had taken other substances besides methamphetamine and psychedelics. Most psychedelic experiences were unplanned, recreational, and combined with other drugs. After the experience, about 59% reported improved mood, 50% improved social functioning, and 34% reduced methamphetamine use. Planning the experience and having less challenging experiences were linked to better outcomes. The findings suggest that psychedelic use may improve mood and social function and reduce substance use in this population, but highlight the importance of context and setting.
Drug and alcohol dependence
November 1, 2020
Sarah A Okey, Madeline H Meier
Regular cannabis users who consume both marijuana (flower) and concentrates (high-THC products like butane hash oil) report that marijuana produces greater positive effects, including more positive affect and enhanced cognitive function, than concentrates do. Negative effects of both forms are minimal. In a survey of 574 past-year users, marijuana was rated as producing greater overall positive effects (mean 5.6 vs. 4.5 for concentrates), and 77.5% preferred marijuana. The findings suggest that for regular users, extreme negative effects from either form are unlikely, and the main difference lies in the positive subjective experience rather than in adverse reactions.
Drug and alcohol dependence
December 1, 2010
James P Zacny, Jenny M Jun
A retrospective analysis of data from nine laboratory studies involving 110 healthy volunteers (38 females, 72 males) found that sex does not modulate the subjective effects of inhaling 30% nitrous oxide. Nitrous oxide produced several subjective effects, including those related to abuse liability such as feeling elated, having pleasant thoughts, and drug liking, but females and males showed similar responses. The authors suggest that future prospective studies could examine other concentrations, measures like choice or analgesic response, and other inhaled general anesthetics to better understand the role of sex in responses to inhalants.
Drug and alcohol dependence
November 1, 2008
James P Zacny, Diana J Walker, Lindsay M Derus
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.
Drug and alcohol dependence
January 4, 2006
Nancy J Beckman, James P Zacny, Diana J Walker
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.
Drug and alcohol dependence
March 1, 2002
Diana J Walker, James P Zacny
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.
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.
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.
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.
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.
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.