Does vitamin B12 deficiency explain psychiatric symptoms in recreational nitrous oxide users? A narrative review

Abstract

Background Recreational use of nitrous oxide (N₂O) is associated with many side effects, of which neurological complications are most common. Nitrous oxide abuse is also associated with psychiatric symptoms, but these have received less attention so far. Vitamin B12 deficiency may play a role in the development of these psychiatric symptoms.

Aims To explore the relationship among the occurrence of recreational nitrous oxide-induced psychiatric symptoms, accompanying neurological symptoms, vitamin B12 status and choice of treatment.

Methods A retrospective search for case reports was conducted across multiple databases (Pubmed, Embase, Web of Science, PsycINFO and CINAHL). Keywords included variants of “nitrous oxide”, “case report” and “abuse”. No restrictions to language or publication date were applied.

Results The search retrieved 372 articles. A total of 25 case reports were included, representing 31 patients with psychiatric complications following nitrous oxide abuse. The most often reported symptoms were: hallucinations (n = 16), delusions (n = 11), and paranoia (n = 11). When neurological symptoms were present, patients were treated more frequently with vitamin B12 supplementation.

Conclusions This review highlights the need to recognize that psychiatric symptoms may appear in association with nitrous oxide use. Approximately half of the cases that presented with nitrous oxide-induced psychiatric complaints did not show neurological symptoms, and their vitamin B12 concentration was often within the hospital's reference range. Psychiatrists and emergency physicians should be aware of isolated psychiatric symptoms caused by recreational nitrous oxide abuse. We suggest asking all patients with new psychiatric symptoms about nitrous oxide use and protocolizing the management of nitrous oxide-induced psychiatric symptoms.

Keywords:

• Nitrous oxide
• laughing gas
• whippets
• psychiatry
• vitamin B12

Acknowledgements

The authors thank Drs. Rumia Bose, MBBS (Psychiatrist at Mondriaan, Institute of Mental Health, the Netherlands) for commenting on the draft version of our manuscript. Drs. Rumia Bose has no conflict of interest to declare.

Author contributions

All authors contributed to the study conception and design. M.C. Paulus, A.M. Wijnhoven, G.C. Maessen and S.R. Blankensteijn contributed to the data collection, the analysis of the results and to the writing of the first draft of the manuscript. All authors commented on previous versions of the manuscript, and read and approved the final manuscript. M.A.G. van der Heyden supervised the project.

Disclosure statement

The authors report no conflict of interest.