Background
Commonly known as laughing gas, ‘nangs’ or ‘whippits.’ It belongs to the inhalant class of drugs.
Can be purchased by anyone 18 or older, typically labeled ‘for food purposes only.’
Legally used in clinical settings like dentist, fuel booster in car racing, and whipped cream propellant
Increasingly popular as recreational substance in teenagers and young adults.
In the USA, 13 million people report using it in their lifetime.
Marked increase in Mortality Rate in the US from 2010-2023: 0.01/100,000 population to 0.06/100,000 population (600% increase)
Pharmacology/Pharmacokinetics
Inhalational anesthetic, analgesic and anxiolytic, rapid onset and disappearing within minutes
Interacts with opioid system, and also is an NMDA antagonist which can cause dopamine disinhibition
This is the main target for anesthetic effect
Abused for its euphoric and hallucinogenic effect lasting 5-20 seconds.
Chronic use associated with neurologic sequalae including neuronal demyelination, Vitamin B12 deficiency causing subacute combined spinal cord degeneration
Inactivates co-factor cobalamin and ultimately leads to disrupted DNA/RNA methylation needed for myelin sheath, blockade of NMDA receptors, and accumulation of reactive oxygen species, in addition to a cascade of metabolic effects that contribute to neurotoxicity.
Gait instability, limb or generalized weakness, paresthesias are initial symptoms
Psychiatric manifestations: hallucinations, anxiety, depression, delirium, memory impairment
Hematologic sequalae are also possible: megaloblastic/pernicious anemias, myelosuppression
Also associated with pulmonary embolism, central venous sinus thrombosis, and DVT
Medical Management
Usual ED supportive care for acute overdose although unlikely given short duration of effects: ABC’s, hemodynamic support
Lesions can be seen on spinal cord MRI
Indirect biomarkers can provide clues that individual may be abusing: Vitamin B12, plasma homocysteine, plasma MMA
For chronic use, treatment involves permanent cessation of nitrous use and high dose IM vitamin B12; prognosis for full recovery of neuropathies is poor
Naltrexone may be helpful in cases of chronic abuse
Withdrawal
No specific withdrawal syndrome reported
References
1. Allan J, Cameron J, Bruno J. A Systematic Review of Recreational Nitrous Oxide Use: Implications for Policy, Service Delivery and Individuals. International Journal of Environmental Research and Public Health. 2022;19(18):11567. doi:10.3390/ijerph191811567
2.Brunt TM, van den Brink W, van Amsterdam J. Mechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review. Int J Mol Sci. 2022;23(23):14747. doi:10.3390/ijms232314747
3. Garakani A, Jaffe RJ, Savla D, et al. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature. The American Journal on Addictions. 2016;25(5):358-369. doi:10.1111/ajad.12372
4. Gernez E, Lee GR, Niguet JP, Zerimech F, Bennis A, Grzych G. Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism. Toxics. 2023;11(12):962. doi:10.3390/toxics11120962
5. Vohra V. Notes from the Field: Recreational Nitrous Oxide Misuse — Michigan, 2019–2023. MMWR Morb Mortal Wkly Rep. 2025;74. doi:10.15585/mmwr.mm7412a3
6. Yockey RA, Hoopsick RA. US Nitrous Oxide Mortality. JAMA Netw Open. 2025;8(7):e2522164. doi:10.1001/jamanetworkopen.2025.22164
7. Zaloum SA, Mair D, Paris A, et al. Tackling the growing burden of nitrous oxide-induced public health harms. The Lancet Public Health. 2025;10(3):e257-e263. doi:10.1016/S2468-2667(24)00298-6