Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature

Amir Garakani, Robert J. Jaffe, Dipal Savla, Alison K. Welch, Caroline A. Protin, Ethan O. Bryson, David M. McDowell

Research output: Contribution to journalReview articlepeer-review

184 Scopus citations


Background/Objectives: Nitrous oxide (N2O) 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 N2O 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 N2O were excluded as were commentaries or personal essays. Clinical presentation, frequency of N2O 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 N2O 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 N2O abuse was correlated with low or low-normal Vitamin B12 (cyanocobalamin) levels (N = 52) and occasionally elevated homocysteine and methylmalonic acid. Conclusions/Scientific Significance: N2O 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 N2O and be able to identify potential N2O abuse. (Am J Addict 2016;25:358–369).

Original languageEnglish (US)
Pages (from-to)358-369
Number of pages12
JournalAmerican Journal on Addictions
Issue number5
StatePublished - Aug 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Clinical Psychology
  • Psychiatry and Mental health


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