Rising Nitrous Oxide Use Has Arrived in Germany

Data from poison control centers

Nitrous oxide abuse has been on the rise in many Western countries for several years, and particularly in countries neighboring Germany such as France and the Netherlands (1, 2). It is used for its euphoria-inducing psychedelic effects. The use of nitrous oxide can, through acute hypoxia and chronic functional vitamin B12 deficiency, cause severe neurological damage (3). The increased reporting on nitrous oxide use also suggests a rise in Germany, although representative data are not yet available.

Poison control centers collect data on acute poisoning cases through their emergency consultation services, thereby providing a cross-section of poisoning incidents in the population and enabling the identification of trends (1). This study analyzed case data from German poison control centers on emergency consultations following nitrous oxide exposure between 2000 and 2023.

Methods

This multicenter, retrospective observational study analyzed anonymized case records from six German poison control centers serving a total of 86% of the German population. The period from 1 January 2000 to 31 December 2023 was examined. All cases of nitrous oxide exposure—including those in the context of mixed intoxications—were included. The number and type of toxins involved, the date of consultation, patient age and sex, the mode of exposure, and the Poisoning Severity Score (PSS) at the time of consultation were recorded. The trend was modeled using a 3-year moving average and negative binomial regression.

Results

A total of 207 cases of nitrous oxide exposure were recorded during the study period. In the regression model, our data showed a significant annual increase in case numbers of 12.2% (p<0.001). Between 2000 and 2020, the 3-year moving average remained below 7 cases per year, subsequently increasing disproportionately by 605% to 38 cases in 2023 (Figure). Those affected were predominantly male (m: 70.8%/136, f: 29.2%/56; n = 192) and had a mean age of 23.6 years (min: 4 years, max: 87 years, 25^th percentile: 17 years, 75^th percentile: 26.3 years). Young adults were by far the most frequently affected age group (18–29 years: 52.1%/86; n = 165), followed by adolescents (14–17 years: 24.2%/40). Abuse was the most commonly reported mode of exposure and predominated in the 14- to 49-year age group (79.4%/131; n = 165). This was followed by accidental (9.1%/15), suicidal (6.1%/10), and occupational exposure (1.8%/3), as well as side effects of medical procedures (3.6%/6) (Table).

Figure

Annual case numbers

Table

Number and percentage distribution of reported nitrous oxide exposures by mode of exposure and age group*

Symptoms were present at the time of emergency consultation in 86.6% (162; n = 187) of cases. The majority of patients exhibited mild symptoms (PSS 1: 59.9%/112). Moderate symptoms were less common (PSS 2: 20.9%/39). Severe symptoms were rarely reported (PSS 3: 5.3%/10), and there was one fatality (PSS 4: 0.5%/1).

In 35.3% (73, n = 207) of cases, mixed intoxication was present. The most frequently used substances alongside nitrous oxide included alcohol (54.4%/37; n = 68), cannabis (28.8%/21), benzodiazepines (15.1%/11), and cocaine (10%/7).

Discussion

Our study indicates a significant rise in nitrous oxide exposure in Germany from 2020 onwards. Due to the lack of data for 2024, it is possible that 2023 was a statistical outlier; however, comparable trends in several Western countries makes this unlikely (1, 2). In our data, too, the increase is predominantly attributable to abuse, with the 18—29 age group affected in more than half of cases (52.1 %) and the 14—17 age group in almost a quarter of cases (24.2%). This alarming trend was already apparent in the 2022 MoSyD study, in which 17% of surveyed 15- to 18-year-old students reported having experimented with nitrous oxide (4). Here, 54% of respondents considered nitrous oxide to be less dangerous than other drugs. This misconception of the health risks is potentially fostered by the legal availability of the substance (1, 4), and is likely transferable to other age groups. The symptoms described as mild to moderate in our data correspond to the typical effects of occasional nitrous oxide use, which is usually without consequence. However, excessive or chronic use can result in severe neurological damage. In such cases, nitrous oxide causes a functional vitamin B12 deficiency, leading to impaired myelin synthesis and subsequent nitrous oxide-induced subacute combined degeneration of the spinal cord (N₂O-SACD) (3). Clinically, patients most frequently present with peripheral neuropathy, ataxia, and paralysis, particularly of the lower limbs (5). More rarely, thromboembolic events and impaired hematopoiesis have also been reported (3). Nitrous oxide was long considered to be non-addictive (2); however, more recent reports suggest that it has addictive potential. Although the consultation data from German poison control centers represent only a snapshot of the overall prevalence, the dramatic increase in nitrous oxide exposure, on the one hand, and the readily preventable serious neurological sequelae, on the other, underscore the need to better inform at-risk groups, regulate the distribution of nitrous oxide, and train primary and acute care providers in the recognition and treatment of N₂O-SACD.

Marc Sören Schmidt*, Ingo Greb*, Martin Ebbecke, Florian Eyer, Maren Hermanns-Clausen, Petra Förster, Dagmar Prasa, Lukas Mödl, David Steindl

Conflict of interest statement MSS, IG, ME, FE, MHC, PF, DP, and DS are members of the German Society for Clinical Toxicology (Gesellschaft für Klinische Toxikologie, GfKT).

IG, FE, MHC, DP, and DS are also members of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT).

In addition, FE is Scientific Advisor to the German journal Zeitschrift Notfall & Rettungsmedizin and a Senior Editorial Member of the journal Clinical Toxicology. IG is a member of the editorial board of the German journal Rettungsdienst (S+K-Verlag).

LM declares that no conflict of interest exists.

Manuscript submitted on 15 April 2025, revised version accepted on12 August 2025.

Translated from the original German by Christine Rye.

Cite this as. DOI: 10.3238/arztebl.m2025.0149

References

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