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Laughing Gas Linked to Myeloneuropathy in Young Asian Males

Researchers have found a predominance of young Asian males among patients who developed myeloneuropathy after recreational use of nitrous oxide (N2O), commonly called 'laughing gas'. 

The study was the largest clinical case series of recreational users of nitrous oxide to date, and seemed to confirm previous suspicions that ethnicity may predispose to neurological damage.

The team studied a series of 119 young people with probable (39) or confirmed (80) myeloneuropathy caused by laughing gas use who presented to NHS teaching hospitals in three of the UK's largest cities: London (56), Birmingham (35), and Manchester (28), between 2014 and 2022. Nearly half of the cases (57) were seen within the last 12 months of the study period, apparently also confirming recent reports of an increase in N2O-related neurological damage, in spite of reportedly falling use.

The study, published online in the Journal of Neurology, Neurosurgery & Psychiatry , found "a predominance of young Asian men" among the cases with N2O-related neurological side effects. 

Most cases were young, in keeping with previous reports, the team said, with an average age of 22 (range 14-39). They noted that nitrous oxide is the second most commonly used recreational drug among 16- to 24-year-olds in the UK. Overall, three-quarters of the patients were male, though in East London this proportion dropped to two-thirds.

Over half of the patients (57%; 68) were of Asian or Asian British ethnicity, with the highest proportion in East London (73%; 41), followed by Birmingham (54%) and Manchester (29%). The researchers contrasted these numbers with population proportions of Asian or Asian British in the same areas according to the latest (2021) National Census data, at 45%, 31%, and 21%, respectively.

Findings May Suggest Genetic Susceptibility

"Asian or Asian British individuals presenting with N2O-related harm appear to be over-represented relative to the proportion of the population that is Asian or Asian British in each region," the researchers said. "This may indicate genetic susceptibility to the nerve damage caused by exposure to the gas, or other, as yet unidentified, social factors." 

The team also noted that users who reported regular N2O consumption on a weekly basis displayed "blood markers indicating that vitamin B12 wasn't functioning normally", and this was the cause of the nerve damage. B12 injections are the main treatment for toxicity, "although these probably only work if nitrous oxide use is discontinued", they said.

Follow up information was available for only 38 patients, but all bar four of them had ongoing symptoms.

Further Investigation 'Urgently Required'

"The possibility that genetic variation affects proteins in relevant metabolic pathways and predisposes individuals to adverse outcomes has been previously raised and should be further investigated," the researchers urged. 

The public health issue "urgently requires more research into the threshold quantity of N2O necessary to consume to cause neurological damage, the natural history of N2O-myeloneuropathy, and optimal treatment," they added.

The paper noted that since the research was accepted, the UK Government had moved to 'ban' retail sales of nitrous oxide. This would involve bringing it into the scope of the Misuse of Drugs Act 1971, and was in part because of concerns that recreational use contributes to anti-social behaviour. As reported by Medscape News UK, this was despite advice against legislation from the Advisory Council on the Misuse of Drugs in its N20 harms assessment report earlier this year. 

However, the study's authors recommended that "Manufacturers and sellers of nitrous oxide should be held accountable for the apparent increase in harm through policy implementation and/or legislation."

The Preventive Neurology Unit is funded by the Barts Charity. DM leads a medical student-run unpaid campaign, 'N2O: Know the Risks', which provides educational teaching sessions in East London on the risks of nitrous oxide.