2026 ECNP Congress

PS01-1009

Nitrous oxide dependence, neurotoxicity and a coordinated municipal response while using municipal waste as surveillance tool: a quasi-experimental implementation study

Mathias Luderer — D. Scholz-Hehn, V. Staat, K. Aydin, K. Graebner, A. Tshagharyan, I. Divé, P. Wagner, U. Meyding-Lamadé, P. Tinnemann, C. Schwark, C. Grefkes, A. Reif · Goethe University Frankfurt- university hospital, Department of Psychiatry- Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany

2026 ECNP Congress

Introduction

Recreational nitrous oxide (N2O) use has escalated rapidly across Europe, particularly among adolescents and young adults, fuelled by cheap, large-volume cylinders marketed at this population [1]. While neurotoxicity through functional vitamin B12 inactivation is well-established, the addictive potential of N2O remains debated [2]. This knowledge gap is mirrored by a monitoring gap: conventional self-report surveys reported a reduction in prevalence of nitrous oxide use in the city of Frankfurt am Main, Germany, while at the same time emergency departments reported escalating severe neurological cases [3]. Despite the rising use of N2O, there is a lack of evidence for legislative or other approaches to restricting access to N2O [4,5].

In response, the City of Frankfurt am Main developed the ‘Frankfurt Rapid Action Model’ (FRAM), a coordinated multi-sectoral intervention targeting commercial supply chains without criminalising users.

Aims

To characterise the psychiatric and neurological phenotype of severe N2O use disorder in hospitalised patients and addiction counselling clients; to evaluate whether a coordinated municipal intervention reduced population-level consumption and clinical burden compared to a control city relying on standard legislative restrictions; and to validate municipal waste surveillance as an objective, real-time monitoring tool.

Methods

We conducted a mixed-methods study combining: (1) clinical sentinel surveillance through retrospective case series from three hospitals and five addiction counselling centres in Frankfurt am Main (January 2022–December 2025), with systematic assessment of ICD-10 dependence criteria, psychiatric comorbidity, and biomarkers; (2) population-level waste surveillance using systematic counts of discarded N2O cylinders in Frankfurt (2023–2025) and the control city Hamburg (2024–2025); (3) quasi-experimental difference-in-differences evaluation of the intervention using Poisson regression with incidence rate ratios (IRR). The ratio of IRRs quantified the relative change in Frankfurt compared to the expected trajectory based on Hamburg.

Results

Among 11 hospitalised patients allowing systematic dependence assessment (mean age 26.3 years; 45% female), ICD-10 dependence syndrome was confirmed in 10 cases (91%). Psychotic symptoms were documented in 6 (55%) cases. Psychiatric comorbidity was highly prevalent. Addiction counselling centres identified 31 clients (mean age 18.4 years; median 16 years), with frequent comorbid attention deficit/hyperactivity disorder, depression, anxiety and intentional self-harm. At the population level, municipal waste surveillance documented an eightfold increase in discarded cylinders from 780 (2023) to 6,300 (2024) in Frankfurt. Following FRAM implementation, Frankfurt’s increase attenuated to 23.5% (IRR 1.24; 95% CI 1.19–1.28), whereas Hamburg surged by 67.7% (IRR 1.68; 95% CI 1.62–1.74) despite earlier sales bans. The ratio of IRRs was 0.74 (95% CI 0.70–0.78; p<0.001), indicating a 26% relative reduction. Neurological admissions at Frankfurt University Hospital declined from a peak of 13 (2024) to 3 (2025).

Conclusions

The proliferation of large-volume N2O cylinders led to a distinct severe addiction phenotype characterised by dependence, neurotoxicity and psychosis, demanding psychiatric attention. Standard legislative bans alone proved insufficient. A coordinated supply-chain intervention alongside preventive strategies achieved rapid population-level consumption reduction, paralleled by declining neurological admissions, offering a transferable model for municipalities confronting this emerging public health crisis. Municipal waste surveillance offers a scalable alternative to biased self-report data.

References

  1. European Union Drugs Agency (EUDA), 2024. Recreational use of nitrous oxide: a growing concern for young people in Europe. EUDA Technical Report. Luxembourg.
  2. Back S, Kroon E, Colyer‐Patel K, Cousijn J. Does nitrous oxide addiction exist? An evaluation of the evidence for the presence and prevalence of substance use disorder symptoms in recreational nitrous oxide users. Addiction 2024; 119: 609–18.
  3. Martens J, Werse B, Friedrichs D, Caspari J, Klaus L. [MoSyD ANNUAL REPORT 2024 - Drug Trends in Frankfurt am Main]. 2025; published online Nov. https://frankfurt.de/-/media/frankfurtde/service-und-rathaus/verwaltung/aemter-und-institutionen/drogenreferat/pdf/mosyd-2024-gesamtbericht.pdf (accessed Jan 4, 2026).
  4. European Union Drugs Agency (EUDA). Other drugs – the current situation in Europe (European Drug Report 2025). 2025; published online June 5. https://www.euda.europa.eu/publications/european-drug-report/2025/other-drugs_en (accessed Nov 16, 2025).
  5. Zaloum SA, Mair D, Paris A, et al. Tackling the growing burden of nitrous oxide-induced public health harms. The Lancet Public Health 2025; 10: e257–63.