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Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature: Toxic Effects of Nitrous Oxide Abuse

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Garakani, Amir, Jaffe, Robert J., Savla, Dipal, Welch, Alison K., Protin, Caroline A., Bryson, Ethan O., McDowell, David M.·2016·The American Journal on Addictions
DOI 10.1111/ajad.12372
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Abstract

BACKGROUND/OBJECTIVES: Nitrous oxide (N2 O) is known to have abuse potential, although debate regarding the toxic effects of such abuse continues. Our objective was to review the case literature and present the neurologic, psychiatric and medical consequences of N2 O abuse. METHODS: A systematic literature review was completed for case reports using keywords "nitrous oxide" with "abuse/abusing" or "misuse/misusing" or "overuse/overusing" or "addiction." Non-English-language cases and cases not involving direct toxic effects of N2 O were excluded as were commentaries or personal essays. Clinical presentation, frequency of N2 O abuse, laboratory studies, imaging, ancillary tests, treatments and outcomes were collected from case reports. RESULTS: Our review returned 335 Pubmed, 204 Web of Science, 73 PsycINFO, 6 CINAHL, 55 EMBASE and 0 Grey Literature results, and after exclusion and removal of duplicates, 91 individual cases across 77 publications were included. There were also 11 publications reporting 29 cases of death related to N2 O abuse. The majority of cases (N = 72) reported neurologic sequelae including myeloneuropathy and subacute combined degeneration, commonly (N = 39) with neuroimaging changes. Psychiatric (N = 11) effects included psychosis while other medical effects (N = 8) included pneumomediastinum and frostbite. Across all cases N2 O abuse was correlated with low or low-normal Vitamin B12 (cyanocobalamin) levels (N = 52) and occasionally elevated homocysteine and methylmalonic acid. CONCLUSIONS/SCIENTIFIC SIGNIFICANCE: N2 O abuse represents a significant problem because of the difficulty involved with identification and the toxicity related to chronic abuse including possible death. Health professionals should be aware of the toxic effects of N2 O and be able to identify potential N2 O abuse. (Am J Addict 2016;25:358-369).

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  • Concerns regarding toxicity and abuse risk, which mostly occur with chronic, high-dose recreational usage, have somewhat obscured promising initial findings of N2O.

    “Concerns regarding toxicity and abuse risk, which mostly occur with chronic, high-dose recreational usage, have somewhat obscured promising initial findings [128].”

    From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [128]

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Authors
Garakani, A., Jaffe, R. J., Savla, D., Welch, A. K., Protin, C. A., Bryson, E. O., & McDowell, D. M.
Affiliations
  • Silver Cross Hospital (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Penn State Milton S. Hershey Medical Center (US)
Corresponding author
Garakani, Amir
ORCID
Venue
The American Journal on Addictions
Publisher
Wiley
Published
2016-04-01
Volume
25
Issue
5
Pages
358-369
ISSN
1055-0496 (ISSN-L)
DOI
10.1111/ajad.12372
OpenAlex
W2328547952
Cited by
279
References
0
Citations by year
2026: 24 · 2025: 36 · 2024: 28 · 2023: 45 · 2022: 36 · 2021: 40 · 2020: 21 · 2019: 26 · 2018: 12 · 2017: 8 · 2016: 3
FWCI
2.53
Type
journal article
Language
en
Open access
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
Locations
  • American Journal on Addictions (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
  • Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
nitrous oxide abuse, neurotoxicity, myeloneuropathy, subacute combined degeneration, psychosis, pneumomediastinum, frostbite, vitamin B12 deficiency, vitamin B12, homocysteine, methylmalonic acid, substance abuse
MeSH terms
Humans, Neurologic Examination, Nitrous Oxide, Vitamin B 12 Deficiency, Behavior, Addictive, Substance-Related Disorders

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