Laughing gas, or nitrous oxide, is often seen as a ‘soft’ drug. However, an emerging epidemic of neurological harm from the gas warrants a preventive public health approach. Devan Mair and Professor Alastair Noyce explain why
Profile: Devan Mair
Devan Mair is a medical student at Barts and the London School of Medicine, Queen Mary University of London and has a Masters in Neuroscience and Translational Medicine.
He leads N2O: Know The Risks; a student-run campaign that provides interactive workshops to young people in East London on the neurological risks of nitrous oxide.
Profile: Professor Alastair Noyce
Professor Alastair Noyce is a consultant neurologist and professor of neurology and neuroepidemiology at the Preventive Neurology Unit at the Wolfson Institute of Population Health, Queen Mary University of London.
He has seen many patients with nitrous oxide-related myeloneuropathy, leading the way with national guidelines for neurologists on management.
Nitrous oxide: a substance of many names
Gas-and-air, laughing gas, Entonox, NOS, N2O, balloons, nangs, canisters, Smartwhips, Fastgas, Goldwhips, cream chargers, whippits. Believe it or not, this is a non-exhaustive list of synonyms for the same thing; nitrous oxide. This colourless and odourless gas is used medically for anaesthesia and industrially in whipped cream propellant and in improving combustion engine performance in cars (made famous in the Fast and the Furious movie franchise).
Image: A three litre can of recreational nitrous oxide. Credit Xofc (CC BY-SA 4.0) https://creativecommons.org/licenses/by-sa/4.0/legalcode
Perhaps one of the most common modern uses of nitrous oxide is as a recreational drug. The effects of nitrous oxide include mood changes (hence the laughing), perceptual changes such as hallucinations, and dizziness.
The biochemical nature of these psychotropic effects is not well understood, although N2O is known to interact with N-methyl-Daspartate (NMDA) and opioid receptors.1
Nitrous oxide is the second most used drug among 16 to 24-year-olds in the UK, partially due to the ease of acquisition in the UK from corner shops and online vendors.
The drug comes in various preparations; canisters, 600g cylinders (approximately equivalent to 72-80 canisters), and supersize 2kg cylinders (approximately 500 canisters). The high from nitrous oxide is short-lived, so people often use many.
Nitrous oxide can cause spinal cord damage
However, an increase in recreational use has been accompanied by a simultaneous rise in cases of nitrous oxide-related myeloneuropathy. This condition particularly affects the spinal cord, causing subacute combined degeneration of the posterior dorsal columns. Across the UK, as well as globally, the reports have surged of young people having trouble walking, loss of sensation, and weakness after using nitrous oxide.
This sort of nerve damage occurs through the loss of myelin. Nitrous oxide causes a functional B12 deficiency, with the gas inactivating the vitamin which prevents the normal formation of myelin. The spinal cord and peripheral nerves are thought to be stripped of their myelin sheath, reducing ordinary saltatory conduction of impulses and resulting in debilitating symptoms.
Some of the symptoms of nitrous oxide-related myeloneuropathy might be surprising. Sensory loss such as loss of fine touch, and pins and needles are common, and often co-incident with loss of balance and weakness. Some patients become wheelchair-bound. However, dysautonomia is frequent, causing unexpected symptoms in young individuals, such as constipation, bladder incontinence, and erectile dysfunction.
Lhermitte’s phenomenon and pseudoathetosis also occur – the former involving an electric shock sensation when moving the neck, and the latter involving involuntary slow writhing movements.2 Similar symptoms can occur in a range of other neurological conditions. However, with the increasing incidence of nitrous oxide-related myeloneuropathy, it must be considered a top clinical differential in those with signs of demyelinating disease.
Image: Nitrous oxide whippits used recreationally as a drug by Dutch youngsters near a school, Utrecht, 2017. Credit: Hansmuller (CC BY-SA 4.0) https://creativecommons.org/licenses/by-sa/4.0/legalcode
Ideally, users get help as soon as possible. At the Royal London Hospital in East London, there is one case of nitrous oxide-related myeloneuropathy approximately every nine days.3 Staff at this site set up a management pathway to better diagnose and treat these cases. Diagnosis of subacute combined degeneration is conclusively made by MRI, however, B12 levels and markers of B12 metabolism (i.e. testing if B12 is inactivated) are recommended. Treatment consists of B12 intramuscular injections that are started as soon as possible and are only thought to work if consumption of nitrous oxide is halted. Recovery is variable; some recover with few residual symptoms, while others have long-term problems with sensation and strength.
The law surrounding nitrous oxide
In the UK, nitrous oxide is illegal to give away or sell for recreational means under the Psychoactive Substances Act 2016. This has not stopped sales under the guise of catering purposes. In 2021, the government commissioned an expert panel on nitrous oxide for the Advisory Council on the Misuse of Drugs (ACMD). In March 2023, this ACMD panel advised in favour of preventive measures to minimise the health effects of nitrous oxide on young people but advised against the complete prohibition of nitrous oxide over concerns of ostracising and criminalising young people. Soon after, the government decided to classify nitrous oxide as a Class C drug to be controlled under the Misuse of Drugs Act 1971.
Image: Devan Mair presenting a recent N2O: Know The Risks workshop.
Our contribution; greater scientific and community awareness
Until recently, treatment of nitrous oxide-related myeloneuropathy was not standardised. The management pathway at the Royal London Hospital has now been adopted into the national guidelines for the Association of British Neurologists to work to achieve standardisation. However, much awareness is still needed among healthcare professionals regarding the presentation and treatment of nitrous oxide-related nerve damage.
There is still much to be researched in this field. Some key questions include: Is there a safe amount of nitrous oxide to consume that will not cause nerve damage?; Is there a level of addiction to nitrous oxide?; and Are there specific genetic and dietary factors that make certain groups at higher risk of nitrous oxide-related myeloneuropathy? While improving treatment is essential, in this area prevention is paramount.
This is a largely avoidable harm that can likely be minimised through effective education and increased awareness in young people. Part of our work has involved setting up a campaign to raise awareness of the risks of nitrous oxide. N2O: Know The Risks provides interactive workshops to young people in East London, aiming to provide education on how nitrous oxide can cause spinal cord damage. Although workshops have so far been delivered to over a thousand young people, the need for more awareness is greater than ever. We hope that the readers of Aether can take away some key points from the NERVE acronym on the action card that we hand out during these workshops – information that might help anyone who might be using nitrous oxide.
Image: A recent N2O: Know The Risks workshop with young people in East London.
N2O: Know The Risks action cards given to young people after an interactive workshop on the neurological risks of nitrous oxide.
1) GILLMAN, M. A. 2021. Opioid Properties of Nitrous Oxide and Ketamine Contribute to Their Antidepressant Actions. Int J Neuropsychopharmacol. England.
2) KEDDIE, S., ADAMS, A., KELSO, A. R. C., TURNER, B., SCHMIERER, K., GNANAPAVAN, S., MALASPINA, A., GIOVANNONI, G., BASNETT, I. & NOYCE, A. J. 2018. No laughing matter: subacute degeneration of the spinal cord due to nitrous oxide inhalation. J Neurol, 265, 1089-1095.
3) PARIS, A., LAKE, L., JOSEPH, A., WORKMAN, A., WALTON, J., HAYTON, T., EVANGELOU, N., LILLEKER, J. B., AYLING, R. M., NICHOLL, D. & NOYCE, A. J. 2023. Nitrous oxide-induced subacute combined degeneration of the cord: diagnosis and treatment. Pract Neurol.
Barts and the London School of Medicine,
Queen Mary University of London.
Professor Alastair Noyce
Wolfson Institute of Population Health,
Queen Mary University of London.