settings Order Article Reprints Open AccessReview Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism by Emeline Gernez 1, Graham Robert Lee 2 [ORCID] , Jean-Paul Niguet 3, Farid Zerimech 1 [ORCID] , Anas Bennis 4 and Guillaume Grzych 1,* 1 CHU de Lille, Centre de Biologie Pathologie Génétique, 59000 Lille, France 2 Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland 3 Service de Neurologie, Hôpital Saint Vincent de Paul–GHICL, 59000 Lille, France 4 Assistance Publique—Hôpitaux de Paris, Service de Neurologie, Groupe Hospitalier Universitaire Paris Sud, Hôpital Bicêtre, 94270 Le Kremlin-Bicêtre, France * Author to whom correspondence should be addressed. Toxics 2023, 11(12), 962; https://doi.org/10.3390/toxics11120962 Submission received: 27 October 2023 / Revised: 22 November 2023 / Accepted: 26 November 2023 / Published: 28 November 2023 (This article belongs to the Section Neurotoxicity) Download keyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract The recreational use of nitrous oxide (N2O), also called laughing gas, has increased significantly in recent years. In 2022, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) recognized it as one of the most prevalent psychoactive substances used in Europe. Chronic nitrous oxide (N2O) exposure can lead to various clinical manifestations. The most frequent symptoms are neurological (sensitive or motor disorders), but there are also other manifestations like psychiatric manifestations or cardiovascular disorders (thrombosis events). N2O also affects various neurotransmitter systems, leading to its anesthetic, analgesic, anxiolytic and antidepressant properties. N2O is very challenging to measure in biological matrices. Thus, in cases of N2O intoxication, indirect biomarkers such as vitamin B12, plasma homocysteine and plasma MMA should be explored for diagnosis and assessment. Others markers, like oxidative stress markers, could be promising but need to be further investigated.