The hidden burden of laughing gas

The frequent presence of silver canisters, or “whippits,” on our streets (even during the covid-19 lockdown) is a visible mark of the increasing incidence of nitrous oxide (N2O) or laughing gas misuse. 

N2O is a colourless gas that has long been pharmaceutically indicated for general anaesthesia and analgesia [1]. The sale of N2O in canisters, as a liquefied compressed gas, is permitted if they are designed and intended to be sold as a food additive (for example, a propellant for whipped cream) for commercial purposes. As a result, N2O canisters are readily available to purchase on the internet (via eBay and Amazon, for example) or via street dealers. The supply of N2O as a recreational drug is illegal under the UK’s Psychoactive Substances Act 2016, however, this has not acted as a deterrent in illicit drug use.

The misuse of laughing gas is “no laughing matter.” Its misuse in high doses has been associated with dose-dependent psychiatric, haematological, and neurological adverse effects and even death. Adverse effects include pulmonary embolism and deep vein thrombosis, skin hyperpigmentation, and more serious neurological damage such as paraplegia. Neurological damage associated with N2O is linked to the inactivation of vitamin B12 (cyanocobalamin) and functional B12 deficiency, leading to the methylation of myelin proteins, which, in turn, causes demyelination within the central and peripheral nervous system. These adverse effects are manifested as subacute combined degeneration (pernicious azotaemia), toxic myelopathy including subacute cervical myelopathy and generalised demyelinated polyneuropathy, and T2 signal hyperintensity in the spinal cord

These adverse events are even more concerning when the prevalence and usage trends of N2O are considered. The 2019 Global Drug Survey reported that N2O  was one of the top 10 most popular drugs used by respondents in the previous year. Similarly, the 2018/2019 Crime Survey for England and Wales reported that among 16 to 24 year olds in the UK, 8.7% (around 552 000 individuals) had used N2O in the past year. In this age group, N2O was the second most popular substance behind cannabis. Survey respondents reported obtaining N2O from friends, family members, dealers, shops, and the internet. Approximately, a quarter of respondents said that it would be easy to obtain N2O in less than 24 hours. 

A report for the All Party Parliamentary Group on new psychoactive substances and volatile substances showed that, after volatile substances, pupils’ early experience of drug use (11 years old and younger) was most likely to involve N2O. Similarly, a 2017 study on drug use and misuse across seven universities in Wales showed that the most commonly used drugs were cannabis, followed by ecstasy, cocaine, and N2O. Its popularity is likely to be linked to its short duration of action and ease of access. 

Despite the scarcity of information on the economic and health burden of N2O, a number of unsafe practices of N2O use have been reported, including inhaling it directly from the nozzle of a whipped cream dispenser, plastic bags, or directly from an N2O tank. There are also the risks of frequent dosing due to its short duration of action and poly-substance misuse with N2O. Reported deaths have been caused by sudden cardiac arrhythmias and/or asphyxiation. When the Office for National Statistics compiled drug related deaths involving N2O in England and Wales they found that on average, five people died from N2O per year between 2013 and 2017, with a total of 29 people dying between 2010 and 2017.

The number of patients presenting to healthcare services with neurological damage due to N2O consumption is expected to rise. The puzzling loophole within this current state of affairs is that N2O misuse is controlled under the Psychoactive Substances Act 2016, and yet N2O canisters or “whippets” are readily available to purchase on the internet. It is clear that the lack of clarity around the regulation of these drugs’ supply and use needs to be imminently addressed. 

Additional harms from N2O have been potentially exacerbated by the disruption of drug markets during the covid-19 pandemic. This disturbance has created notable shifts in drug consumption trends, with the shortages of certain illicit drugs leading to increasing consumption of more accessible substances. Since N2O is legally available via online outlets, it could present a viable alternative for people who use drugs. Many commentators have also expressed fears that the impact of lockdown and its attendant mental health stresses will lead to an increase in harmful use of drugs and alcohol. Finally, it is important to note that since N2O is administered by inhalation, with large amounts possibly leading to hypoxia, it thus risks making users develop possible additional complications if they are infected with the coronavirus. 

Tighter regulations around the sale of N2O online need to be imposed by the government. We would suggest that this should include the provision of identification at purchase, raising the age of sale to people aged over 25, restricting quantities per purchase, and prosecuting those suppliers who are targeting sales of N2O canisters for recreational purposes. In conjunction with tighter regulations on the sale of N2O, a harm reduction programme led by healthcare professionals, and with a specific focus on N2O misuse in young people, needs to be developed and implemented nationally.

  1. British Pharmacopoeia 2020 (online) – Volume II – Monographs: Medicinal and Pharmaceutical Substances – Nitrous Oxide (Ph. Eur. monograph 0416).

Amira Guirguis is a pharmacist and the MPharm programme director at Swansea University Medical School. Her research has included in-field drug detection and classification, harm reduction via pharmacist-led “Drug Checking,” drug education, and public health interventions related to substance misuse.

Competing interests: Amira Guirguis receives and has received funding from grant awarding bodies for drug detection research.

Luigi Martini is the chief scientist at the Royal Pharmaceutical Society. He has a keen interest in pharmacists playing a role in drug education and public health interventions related to substance misuse.

Competing interests: None to declare

Mair Davies is the former director for Wales at the Royal Pharmaceutical Society. She is also keen for pharmacists to play a part in drug education and public health interventions related to substance misuse.

Competing interests: None to declare.