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Open Access 13-04-2024 | Nitrous Oxide | Invited Review

The boon and bane of nitrous oxide

Authors: Golo Kronenberg, Georgios Schoretsanitis, Erich Seifritz, Sebastian Olbrich

Published in: European Archives of Psychiatry and Clinical Neuroscience

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Abstract

Nitrous oxide (N2O) has been known since the end of the eighteenth century. Today, N2O plays a huge role as a greenhouse gas and an ozone-depleting stratospheric molecule. The main sources of anthropogenic N2O emissions are agriculture, fuel combustion, wastewater treatment, and various industrial processes. By contrast, the contribution of medical N2O to the greenhouse effect appears to be small. The recreational and medical uses of N2O gradually diverged over time. N2O has analgesic and anesthetic effects, making it widely used in modern dentistry and surgery. New research has also begun studying N2O’s antidepressant actions. N-methyl-D-aspartate (NMDA) antagonism and opioid effects are believed to be the main underlying biochemical mechanisms. At this point, numerous questions remain open and, in particular, the conduct of larger clinical trials will be essential to confirm N2O’s use as a rapid-acting antidepressant. The N2O concentration delivered, the duration of a single inhalation, as well as the number of inhalations ultimately required, deserve to be better understood. Finally, the non-medical use of N2O has gained significant attention in recent years. Sudden deaths directly attributed to N2O are primarily due to asphyxia. Heavy, chronic N2O use may result in vitamin B12 deficiency, which, among other things, may cause megaloblastic anemia, venous thrombosis, myeloneuropathy, and skin pigmentation. Helpful biochemical tests include homocysteine and methylmalonic acid. The centerpiece of treatment is complete cessation of N2O use together with parenteral administration of vitamin B12.
Literature
1.
go back to reference American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. APA, ArlingtonCrossRef American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders. APA, ArlingtonCrossRef
4.
go back to reference Barbosa L, Leal I, Timóteo AT, Matias T (2000) Acute megaloblastic anemia caused by inhalation of nitrous oxide in a patient with multiple autoimmune pathology. Acta Med Port 13(5–6):309–312PubMed Barbosa L, Leal I, Timóteo AT, Matias T (2000) Acute megaloblastic anemia caused by inhalation of nitrous oxide in a patient with multiple autoimmune pathology. Acta Med Port 13(5–6):309–312PubMed
7.
go back to reference Block RI, Ghoneim MM, Kumar V, Pathak D (1990) Psychedelic effects of a subanesthetic concentration of nitrous oxide. Anesth Prog 37(6):271–276PubMedPubMedCentral Block RI, Ghoneim MM, Kumar V, Pathak D (1990) Psychedelic effects of a subanesthetic concentration of nitrous oxide. Anesth Prog 37(6):271–276PubMedPubMedCentral
13.
go back to reference EPA (2023) United States Environmental Protection Agency: understanding global warming potentials. Last updated on April 18, 2023 (retrieved on October 19, 2023) EPA (2023) United States Environmental Protection Agency: understanding global warming potentials. Last updated on April 18, 2023 (retrieved on October 19, 2023)
20.
go back to reference Haynes WM (ed) (2014) CRC handbook of chemistry and physics, 95th edn. CRC Press LLC, Boca Raton Haynes WM (ed) (2014) CRC handbook of chemistry and physics, 95th edn. CRC Press LLC, Boca Raton
24.
go back to reference IPCC (2013) Climate change 2013: the physical science basis. In: Stocker TF, Qin D, Plattner GK, Tignor M, Allen SK, Boschung J, Nauels A, Xia Y, Bex V, Midgley PM (eds) Contribution of working group i to the fifth assessment report of the intergovernmental panel on climate change. Cambridge University Press, Cambridge, New York IPCC (2013) Climate change 2013: the physical science basis. In: Stocker TF, Qin D, Plattner GK, Tignor M, Allen SK, Boschung J, Nauels A, Xia Y, Bex V, Midgley PM (eds) Contribution of working group i to the fifth assessment report of the intergovernmental panel on climate change. Cambridge University Press, Cambridge, New York
28.
go back to reference Kety SS, Merel MH, Broomell HT, Rhode CB (1948) The solubility of nitrous oxide in blood and brain. J Biol Chem 173(2):487–496CrossRefPubMed Kety SS, Merel MH, Broomell HT, Rhode CB (1948) The solubility of nitrous oxide in blood and brain. J Biol Chem 173(2):487–496CrossRefPubMed
29.
go back to reference Kim WSH, Dimick MK, Omrin D, Mitchell RHB, Riegert D, Levitt A, Schaffer A, Belo S, Iazzetta J, Detzler G, Choi M, Choi S, Herrmann N, McIntyre RS, MacIntosh BJ, Orser BA, Goldstein BI (2023) Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: focus on cerebrovascular target engagement. Bipolar Disord 25(3):221–232. https://doi.org/10.1111/bdi.13288CrossRefPubMed Kim WSH, Dimick MK, Omrin D, Mitchell RHB, Riegert D, Levitt A, Schaffer A, Belo S, Iazzetta J, Detzler G, Choi M, Choi S, Herrmann N, McIntyre RS, MacIntosh BJ, Orser BA, Goldstein BI (2023) Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: focus on cerebrovascular target engagement. Bipolar Disord 25(3):221–232. https://​doi.​org/​10.​1111/​bdi.​13288CrossRefPubMed
30.
go back to reference Knuf K, Maani CV (2023) Nitrous oxide. StatPearls. StatPearls Publishing, Treasure Island Knuf K, Maani CV (2023) Nitrous oxide. StatPearls. StatPearls Publishing, Treasure Island
38.
go back to reference Nagele P, Palanca BJ, Gott B, Brown F, Barnes L, Nguyen T, Xiong W, Salloum NC, Espejo GD, Lessov-Schlaggar CN, Jain N, Cheng WWL, Komen H, Yee B, Bolzenius JD, Janski A, Gibbons R, Zorumski CF, Conway CR (2021) A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression. Sci Transl Med 13(597):ebe1376. https://doi.org/10.1126/scitranslmed.abe1376CrossRef Nagele P, Palanca BJ, Gott B, Brown F, Barnes L, Nguyen T, Xiong W, Salloum NC, Espejo GD, Lessov-Schlaggar CN, Jain N, Cheng WWL, Komen H, Yee B, Bolzenius JD, Janski A, Gibbons R, Zorumski CF, Conway CR (2021) A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression. Sci Transl Med 13(597):ebe1376. https://​doi.​org/​10.​1126/​scitranslmed.​abe1376CrossRef
40.
go back to reference Nunn JF (1984) Interaction of nitrous oxide and vitamin B12. Trends Pharmacol Sci 5:225–227CrossRef Nunn JF (1984) Interaction of nitrous oxide and vitamin B12. Trends Pharmacol Sci 5:225–227CrossRef
44.
46.
go back to reference Tian H, Xu R, Canadell JG, Thompson RL, Winiwarter W, Suntharalingam P, Davidson EA, Ciais P, Jackson RB, Janssens-Maenhout G, Prather MJ, Regnier P, Pan N, Pan S, Peters GP, Shi H, Tubiello FN, Zaehle S, Zhou F, Arneth A, Battaglia G, Berthet S, Bopp L, Bouwman AF, Buitenhuis ET, Chang J, Chipperfield MP, Dangal SRS, Dlugokencky E, Elkins JW, Eyre BD, Fu B, Hall B, Ito A, Joos F, Krummel PB, Landolfi A, Laruelle GG, Lauerwald R, Li W, Lienert S, Maavara T, MacLeod M, Millet DB, Olin S, Patra PK, Prinn RG, Raymond PA, Ruiz DJ, van der Werf GR, Vuichard N, Wang J, Weiss RF, Wells KC, Wilson C, Yang J, Yao Y (2020) A comprehensive quantification of global nitrous oxide sources and sinks. Nature 586(7828):248–256. https://doi.org/10.1038/s41586-020-2780-0CrossRefPubMed Tian H, Xu R, Canadell JG, Thompson RL, Winiwarter W, Suntharalingam P, Davidson EA, Ciais P, Jackson RB, Janssens-Maenhout G, Prather MJ, Regnier P, Pan N, Pan S, Peters GP, Shi H, Tubiello FN, Zaehle S, Zhou F, Arneth A, Battaglia G, Berthet S, Bopp L, Bouwman AF, Buitenhuis ET, Chang J, Chipperfield MP, Dangal SRS, Dlugokencky E, Elkins JW, Eyre BD, Fu B, Hall B, Ito A, Joos F, Krummel PB, Landolfi A, Laruelle GG, Lauerwald R, Li W, Lienert S, Maavara T, MacLeod M, Millet DB, Olin S, Patra PK, Prinn RG, Raymond PA, Ruiz DJ, van der Werf GR, Vuichard N, Wang J, Weiss RF, Wells KC, Wilson C, Yang J, Yao Y (2020) A comprehensive quantification of global nitrous oxide sources and sinks. Nature 586(7828):248–256. https://​doi.​org/​10.​1038/​s41586-020-2780-0CrossRefPubMed
47.
go back to reference Wagner SA, Clark MA, Wesche DL, Doedens DJ, Lloyd AW (1992) Asphyxial deaths from the recreational use of nitrous oxide case reports. J Forensic Sci 37(4):1008–1015CrossRefPubMed Wagner SA, Clark MA, Wesche DL, Doedens DJ, Lloyd AW (1992) Asphyxial deaths from the recreational use of nitrous oxide case reports. J Forensic Sci 37(4):1008–1015CrossRefPubMed
Metadata
Title
The boon and bane of nitrous oxide
Authors
Golo Kronenberg
Georgios Schoretsanitis
Erich Seifritz
Sebastian Olbrich
Publication date
13-04-2024
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Psychiatry and Clinical Neuroscience
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-024-01801-3