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

Am J Addict. 2016 Aug;25(5):358-69. doi: 10.1111/ajad.12372. Epub 2016 Apr 1.


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).

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Behavior, Addictive
  • Humans
  • Neurologic Examination
  • Nitrous Oxide* / metabolism
  • Nitrous Oxide* / pharmacology
  • Substance-Related Disorders* / complications
  • Substance-Related Disorders* / diagnosis
  • Substance-Related Disorders* / physiopathology
  • Substance-Related Disorders* / psychology
  • Vitamin B 12 Deficiency / etiology
  • Vitamin B 12 Deficiency / prevention & control


  • Nitrous Oxide