Trends in nitrous oxide abuse and misuse: a 22-year analysis of United States poison center data

Nitrous oxide is widely available for medical, industrial, and culinary use. However, its euphoric effects and accessibility have contributed to increasing recreational abuse/misuse. Chronic exposure disrupts vitamin B₁₂ function, resulting in potentially severe neurologic and psychiatric complications. Although case reports suggest a rise in abuse/misuse, trends in the United States remain poorly characterized.

We conducted a retrospective analysis of intentional nitrous oxide abuse/misuse reported to the National Poison Data System^® from 2003 through 2024. Included cases involved individuals aged 13 years and older, in whom nitrous oxide was identified as the primary substance. Data were analyzed for demographic characteristics, clinical effects, treatments, and outcomes using standardized coding definitions.

Of 3,632 cases initially identified, 1,751 met the inclusion criteria. Most were male (63%), and most exposures occurred in private residences (85%). Individuals aged 20-29 years accounted for the largest proportion (37%) of cases. Annual cases rose from 28 in 2003 to 401 in 2024, a 1,332% increase. Over half (55%) of the exposures resulted in the moderate or major clinical effects, including ataxia (11%), numbness (12%), and confusion (14%). Hospital admission occurred in 29% of cases, with 10% admitted to the intensive care unit. Vitamin B₁₂ and folate supplementation were documented in only 6.3% of cases.

These findings demonstrate a sustained and substantial increase in reported intentional nitrous oxide abuse/misuse over two decades in the United States, with a notable rise in cases involving neurologic injury and functional impairment. The high proportion of single-substance exposures and limited use of targeted treatment suggest underrecognition of both the diagnosis and its potential severity. Emerging formulations, including flavored high-volume tanks, may be contributing to this trend.

Intentional nitrous oxide abuse/misuse reported to United States poison centers has risen sharply in both frequency and severity in the United States. Improved clinical awareness, regulatory oversight, and public health interventions are needed to address this growing toxicologic concern.