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Review
. 2023 Nov 28;11(12):962.
doi: 10.3390/toxics11120962.

Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism

Emeline Gernez  1 , Graham Robert Lee  2 , Jean-Paul Niguet  3 , Farid Zerimech  1 , Anas Bennis  4 , Guillaume Grzych  1
Affiliations
Review

Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism

Emeline Gernez et al. Toxics. .

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.

Keywords: addiction; cobalamin; homocysteine; methylmalonic acid; neurology; neuropathy; nitrous oxide; toxicity; vitamin; vitamin B12.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Clinical manifestations related to nitrous oxide intoxication.
Figure 2
Figure 2
Main neurological effects of Nitrous Oxide, neurotransmitter modulation and receptor targets. Red arrow for inhibition and green arrow for activation.
Figure 3
Figure 3
Hypothetic impact of N2O on metabolism. SAH: S-adenosyl-homocysteine, SAM: S-adenosyl-methionine, MTR: methionine synthase, MTRR: methionine synthase reductase, THF: tetrahydrofolate, MMA: methylmalonic acid. Red arrow for major pathway in case of cobalamin oxidation.
See this image and copyright information in PMC

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