Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review
The recreational use of nitrous oxide (N<sub>2</sub>O) has increased over the years. At the same time, more N<sub>2</sub>O intoxications are presented to hospitals. The incidental use of N<sub>2</sub>O is relatively harmless, but heavy, frequent and chronic use co...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14747 |
| _version_ | 1797463129683132416 |
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| author | Tibor M. Brunt Wim van den Brink Jan van Amsterdam |
| author_facet | Tibor M. Brunt Wim van den Brink Jan van Amsterdam |
| author_sort | Tibor M. Brunt |
| collection | DOAJ |
| description | The recreational use of nitrous oxide (N<sub>2</sub>O) has increased over the years. At the same time, more N<sub>2</sub>O intoxications are presented to hospitals. The incidental use of N<sub>2</sub>O is relatively harmless, but heavy, frequent and chronic use comes with considerable health risks. Most importantly, N<sub>2</sub>O can inactivate the co-factor cobalamin, which, in turn, leads to paresthesia’s, partial paralysis and generalized demyelinating polyneuropathy. In some patients, these disorders are irreversible. Several metabolic cascades have been identified by which N<sub>2</sub>O can cause harmful effects. Because these effects mostly occur after prolonged use, it raises the question of whether N<sub>2</sub>O has addictive properties, explaining its prolonged and frequent use at high dose. Several lines of evidence for N<sub>2</sub>O’s dependence liability can be found in the literature, but the underlying mechanism of action remains controversial. N<sub>2</sub>O interacts with the opioid system, but N<sub>2</sub>O also acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, by which it can cause dopamine disinhibition. In this narrative review, we provide a detailed description of animal and human evidence for N<sub>2</sub>O-induced abuse/dependence and for N<sub>2</sub>O-induced neurotoxicity. |
| first_indexed | 2024-03-09T17:46:17Z |
| format | Article |
| id | doaj.art-3710467e2e8143a5a6bce0d548d1a0e5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:46:17Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3710467e2e8143a5a6bce0d548d1a0e52023-11-24T11:07:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231474710.3390/ijms232314747Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative ReviewTibor M. Brunt0Wim van den Brink1Jan van Amsterdam2Department of Psychiatry, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The NetherlandsDepartment of Psychiatry, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The NetherlandsDepartment of Psychiatry, Amsterdam UMC, Location Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The NetherlandsThe recreational use of nitrous oxide (N<sub>2</sub>O) has increased over the years. At the same time, more N<sub>2</sub>O intoxications are presented to hospitals. The incidental use of N<sub>2</sub>O is relatively harmless, but heavy, frequent and chronic use comes with considerable health risks. Most importantly, N<sub>2</sub>O can inactivate the co-factor cobalamin, which, in turn, leads to paresthesia’s, partial paralysis and generalized demyelinating polyneuropathy. In some patients, these disorders are irreversible. Several metabolic cascades have been identified by which N<sub>2</sub>O can cause harmful effects. Because these effects mostly occur after prolonged use, it raises the question of whether N<sub>2</sub>O has addictive properties, explaining its prolonged and frequent use at high dose. Several lines of evidence for N<sub>2</sub>O’s dependence liability can be found in the literature, but the underlying mechanism of action remains controversial. N<sub>2</sub>O interacts with the opioid system, but N<sub>2</sub>O also acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, by which it can cause dopamine disinhibition. In this narrative review, we provide a detailed description of animal and human evidence for N<sub>2</sub>O-induced abuse/dependence and for N<sub>2</sub>O-induced neurotoxicity.https://www.mdpi.com/1422-0067/23/23/14747nitrous oxideN<sub>2</sub>Odependenceneurotoxicitycobalamindopamine |
| spellingShingle | Tibor M. Brunt Wim van den Brink Jan van Amsterdam Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review International Journal of Molecular Sciences nitrous oxide N<sub>2</sub>O dependence neurotoxicity cobalamin dopamine |
| title | Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review |
| title_full | Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review |
| title_fullStr | Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review |
| title_full_unstemmed | Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review |
| title_short | Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review |
| title_sort | mechanisms involved in the neurotoxicity and abuse liability of nitrous oxide a narrative review |
| topic | nitrous oxide N<sub>2</sub>O dependence neurotoxicity cobalamin dopamine |
| url | https://www.mdpi.com/1422-0067/23/23/14747 |
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