Recreational nitrous oxide use in Europe: situation, risks, responses

Key findings

Nitrous oxide is a gas that is inhaled recreationally for its rapid but short-lived feelings of euphoria, relaxation, calmness, and sense of detachment.

While it has been used for almost 250 years, its use has increased in some European countries since 2010. This became a particular concern from around 2017–18, when it became available in more shops and in larger quantities.

The popularity of nitrous oxide is explained by its easy availability, low price, short-lived effects, and the general perception by users that it is a relatively safe and socially acceptable drug.

 Read all key findings  

Background

For almost 250 years, nitrous oxide, commonly known as laughing gas, has been inhaled for its rapid but short-lived feelings of euphoria, relaxation, calmness, and sense of detachment.

Despite this long-standing use, the popularity of the gas has varied greatly, with perhaps three notable periods of interest as a recreational drug.

The first was shortly after its discovery in 1772, when it was used by the British upper class at ‘laughing gas parties’ and as a source of amusement at fairs and music halls.

The second was from the late 1960s. An important driver was the growing use of the gas in dentistry to relieve pain and reduce anxiety, that spilled out into the emerging drug cultures. This is perhaps best documented in the United States. Only a few people used it, as it was relatively difficult to obtain in anything other than large cylinders. It was mostly used with a face mask or from filling a plastic bag that was placed over the head — a cumbersome and dangerous way of using — may have also played a role in limiting its initial spread. Soon, injures from this led to the use of party balloons that were filled from cylinders — making it easier to use, and more appealing.

By the early 1970s, it was being used by university students and at music festivals for 0.25¢ a balloon. Students sourced it either from cylinders, cans of whipped cream — and perhaps most importantly — small cartridges of the gas supposed to be used to make whipped cream, but that were sourced from head shops. A study of around 500 medical and dental students at one US university between 1976 and 1978 found that 16% (84) had used nitrous oxide recreationally. Of these, around 30% had used cylinders and almost 50% had used whipped cream cans or cartridges.

Since then, the use of nitrous oxide bubbled away in the background as a ‘cheap’ legal high. The occasional report of injury or deaths — usually caused by asphyxiation as a result of using a face-mask or plastic bag — sometimes leading to concerns and discussions on regulatory responses.

The third period begins around 2010 — although its origins likely date to the 1990s, where interest was (re)kindled first in the party scene and raves, and then music festivals and clubs.

What distinguishes the current period from the first two is that nitrous oxide is now widely available. It is cheap and easier to buy and to use. Key to its growing popularity has been the widespread availability of the small, inexpensive cartridges of nitrous oxide used to make whipped cream. These are used to fill party balloons, from which the gas is then inhaled. There is also a perception that nitrous oxide is safe. It is easy to buy the cartridges from legitimate sources, including convenience stores, supermarkets and online suppliers. In addition, a profitable and expanding supply chain has developed, with specialised internet stores directly promoting the gas for its recreational use or offering it under the guise of its use to make whipped cream. It is also the availability of cartridges in large quantities that is responsible for increase in use. In some areas, social media plays an important role in advertising and selling the drug. Use by more young people, including teenagers inexperienced with drug use, also characterises this current period.

Most people use small quantities of nitrous oxide occasionally, perhaps one to three balloons in a session, a few times a year. Although it is not possible to define a ‘safe’ level of use, and this kind of consumption will not be risk free, this appears to pose limited health risks in comparison to more intensive patters of use. There is also a smaller, but significant, increase in the number of people who use greater quantities of the gas more frequently and for longer periods of time. Some develop problematic use as a result. The short-lived effects of the gas are often cited as a reason for further use in the same session. It is unclear what dose causes chronic toxicity, although the greater the amount used, the greater the risk. Most poisoning cases involve regular or heavy use, at least over a few months (see box below).

This increased use has become a particular concern from around 2017–18. Greater visibility and awareness is partly responsible for this. Suppliers also started selling larger cylinders of the gas, deliberately targeting the recreational market — making the gas significantly cheaper and promoting broader, as well as more regular and heavier, use.

Mirroring this is a small but significant increase in reports of poisonings to poison centres. In Denmark, cases rose from 16 in 2015, to 62 in 2019, 90 in 2020, and 73 in 2021. In France, 134 cases were reported in 2020 — up from 46 in 2019 and 10 in 2017. While in the Netherlands, cases rose from 13 in 2015 to 128 in 2019, 144 in 2020, and 98 in 2021.

More generally, the renewed interest in nitrous oxide in Europe and elsewhere has seen an increase in cases reported in the medical literature (Figure 1).

 

The source data for this graphic is available in the table at the bottom of this page.

In both cases, much of this is neurotoxicity, often related to regular or heavier use. Large cylinders can also cause severe frostbite (burns caused by exposure to freezing) and lung injuries due to their high pressure. While car accidents caused by driving either intoxicated or while trying to fill balloons have significantly increased in at least in the Netherlands. Littering of used cartridges and balloons have also been highlighted as issues.

Despite this, our understanding of the use, risks, and effective responses are limited, partly because this level of recreational use is relatively new.

Finally, nitrous oxide is a potent greenhouse gas and major cause of the destruction of the ozone layer. The contribution from recreational use is minor compared to other sources, but requires research.

Situation and risks

Use and acute effects

Most people get their nitrous oxide from small cartridges of the gas called ‘whipped cream chargers’. Other English names for the cartridges include ‘canisters’, ‘bulbs’, and 'whippets' (after one of the original major brand names from the 1930s) (Figure 2). These are small pressurised metal cartridges containing 8 grams of liquid nitrous oxide that release around 4 litres of gas when opened. They are intended for use with whipped cream dispensers in the home and by the food industry to make whipped cream, desserts, foams, as well as infuse flavours into drinks.

For recreational use, the cartridges are opened using an empty whipped cream dispenser. This has a holder for the cartridge, and screwing the holder into the dispenser causes a sharp pin to pierce the foil cap at the narrow end of the cartridge, releasing the gas into the dispenser (causing a hissing sound). A balloon is placed over the end of the nozzle of the dispenser. Pressing the lever of the dispenser releases the gas into the balloon. The gas is then inhaled from the balloon, and either exhaled directly to the air or rebreathed into the balloon for extra effect.

Figure 2. A ‘cracker’ used to open nitrous oxide cartridges without the need for a whipped cream dispenser, and balloon

Source: drugsinfo.nl – Trimbos-Instituut.

A cheaper, portable, and more discreet way to use the gas without a whipped cream dispenser is to use a ‘cracker’. This is a pocket-sized cylindrical metal device composed of a holder for the cartridge and a lid. Inserting a cartridge into the holder and screwing on the lid clockwise pushes a pin into the foil cap, piercing it — or ‘cracking’ it open. A balloon is placed over the lid, and turning it anti-clockwise releases the gas into the balloon (Figure 2). Crackers get freezing cold when the nitrous oxide is released into the balloon and may cause cold burns to the hands. A rubber insulating sleeve around the cracker or wearing gloves can prevent this.

Most users use one 8-gram cartridge per balloon, and perhaps 1 to 3 cartridges in a session. Some regular and heavier users may add two cartridges to a balloon or use much greater quantities in a session, either from cartridges or cylinders. In the Netherlands, the sale of ‘extra-large balloons’ (30 cm) may lead to larger amounts of the gas being used compared with the usual balloon size (22 cm).

Rarely, users may connect a cylinder of nitrous oxide to a tube from which they inhale, or use a face mask or plastic bag which is placed over the head to give a longer-lasting supply of the gas. In some cases, 8-gram cartridges have also been used with bags. This poses an extremely high risk of life-threatening hypoxia and death from asphyxiation. Similarly, release of the gas into an enclosed space without adequate ventilation, such as a car, can also be fatal. While these are extremely uncommon ways of using the gas, they are a frequent feature of the deaths from accidental asphyxiation reported in the medical literature.

A few people inhale the gas directly from whipped cream dispensers, crackers, cartridges or cylinders. This poses an extremely high risk of severe cold burns and lung injury. The gas is freezing when it is released from these containers (−40 to −55 °C). Within seconds, it can burn the nose, lips, mouth, throat, vocal cords and lungs. In some cases, the swelling can obstruct the airway, which can be life-threatening and require urgent medical treatment to prevent suffocation. The gas is also under high pressure and can rupture lung tissue when inhaled directly. Cylinders are under much greater pressure than cartridges and therefore pose a higher risk of pressure injuries. Releasing the nitrous oxide into a balloon first helps to warm the gas and normalise the pressure before inhaling. Even so, rare cases of burns to the throat have been reported after inhaling from a balloon.

According to the Danish Poison Centre, the recent switch from cartridges to larger cylinders has led to an increase in frostbite and lung injuries.

The effects of the gas are very rapid, but short-acting. They start almost immediately, peak at about 10-30 seconds after inhalation, and end within 1-5 minutes.

The subjective effects combine feelings of euphoria, relaxation, calmness and distortions of perception, such as sensation, time and space. The euphoria may be accompanied by giggling or laughter. The distortions may affect hearing and sight. The effects are described as a ‘dreamy’ state, ‘psychedelic-like’, or as a general feeling of detachment ('dissociation'). Occasionally, hallucinations are reported, particularly with longer periods of exposure to the gas.

Common adverse effects from using small amounts include dizziness, light-headedness, disorientation, headache and a generalised tingling sensation. Nausea and fainting may also occur, as may temporary loss of coordination and balance. In some cases, users may vomit, which poses a risk of aspiration (breathing the vomit into the lungs) if consciousness is reduced. Some of the effects are from hypoxia caused by a temporary lack of oxygen, which may also cause seizures.

The adverse effects are generally minor and resolve within a short period of time after the user stops breathing the gas. However, some effects, such as light-headedness, dizziness and general impairment, can continue for 30 minutes or so. Using larger amounts of gas in a single session causes a higher number of these adverse effects.

Acute poisoning requiring medical treatment is relatively uncommon. Typically, it involves short-lived disorientation, and injuries from falls caused by fainting or loss of coordination and balance while intoxicated. Occasionally, hallucinations may also require treatment.

Due to disorientation and general impairment, people using nitrous oxide should not drive, ride bikes or scooters or operate machinery. Some people do not view using nitrous oxide while driving as dangerous. In the Netherlands, the number of incidents involving nitrous oxide and driving increased by 80 % between 2019 and 2021 (2 652 to 4 860 incidents). Some incidents relate to driving while intoxicated; others to filling balloons while driving. However, proving use of the gas is difficult in these cases.

Deaths involving nitrous oxide are rare. In most cases, the cause is accidental asphyxiation from breathing the gas using a mask or plastic bag over the head without sufficient oxygen. Deaths may also occur from using the gas in a confined space, such as a car.

More frequent, heavier use of nitrous oxide increases the risk of serious harms such as neurotoxicity. Larger cylinders also pose a greater risk of severe frostbite injuries, typically a result of clamping the cylinder between the thighs while filling the balloons. As the gas is released from the tank to fill the balloon, the cylinder walls can cool down to freezing, especially if the gas is used rapidly. This causes the skin and underlying tissue in contact with the tank to freeze. Users may not be aware of the injury because of the analgesic effect of the nitrous oxide and possibly the cold itself. They are also unlikely to be aware of the severity of the burn, as, initially, the wounds may be like first-degree burns involving mild redness or second-degree burns with blisters. Over the next few days, they can progress to severe third-degree burns.

Early assessment and treatment is essential and may require referral to specialist burn centres. In some cases, treatment may involve multiple surgeries and skin transplantation. Over a five-month period between January and June 2019, 19 patients requiring specialist care for burns caused by cylinders were reported in the Netherlands. Doctors have highlighted issues such as a delay in presentation and referral, which may be partly due to unfamiliarity with this new type of injury and embarrassment on the part of the patient.

The gas may also be used with other substances, such as alcohol, cannabis and MDMA, to enhance their effect or produce different effects. Using other drugs may impair judgement in terms of the amount of nitrous oxide used or 'how to use it without causing injury'.

There is a risk of additive depressant effects when nitrous oxide is used with drugs having a central depressant action. These include alcohol, benzodiazepines and opioids. The extent to which nitrous oxide is used with other depressants is unknown.

The gas causes fires to burn hotter, faster and more intensely. People must not smoke when using the gas and must avoid other sources of ignition.

Chronic effects

Nitrous oxide causes dose-dependent chronic toxicity, with regular and heavy use posing the greatest risk. Overall, how the gas causes these effects is not fully understood. The irreversible inactivation of vitamin B12 in the body plays an important role. It has also been suggested that effects on the N-methyl-D-aspartate (NMDA) glutamate receptor may be involved. Other contributing factors may include hypoxia and acidosis (overproduction of acid, which builds up in the blood and other parts of the body) from using the gas without oxygen.

Vitamin B12 is an essential vitamin, meaning that the body cannot make it itself and it must come from the diet. Sources include meat, fish, dairy or use of a vitamin supplement. Among other functions, vitamin B12 is needed for healthy nerve functioning and for making DNA. Some vegetarians and vegans in particular may have subclinical vitamin B12 deficiency, which may predispose them to a greater risk of chronic toxicity.

The most significant chronic effect of nitrous oxide is neurotoxicity, discussed below. In addition, psychiatric symptoms such as altered mental state, hallucinations, psychotic episodes and mood disturbances have been reported, typically in patients with neurotoxicity. The gas may also cause disorders of the blood, such as anaemia. Finally, rare cases of thrombosis (where a blood clot forms) and embolism (where a clot blocks normal blood flow) as well as heart attacks have been reported recently in heavy users. These and other less common adverse effects are discussed in the full report.

In addition to the effects caused by nitrous oxide itself, frequent, repeated hypoxia may also cause a range of harms. These include brain damage that can result in cognitive impairment that affect a person's everyday life, such as difficulty in concentrating, remembering, learning new things, or making decisions.

Neurotoxicity

Nitrous oxide damages the peripheral and central nervous system. How it causes this neurotoxicity is not fully understood, but it involves inactivation of vitamin B12 and is dose dependent. Cases were first described in the late 1970s in dentists who frequently used the gas recreationally or were exposed to it through work.

The signs and symptoms of neurotoxicity can be highly variable and sometimes vague and subtle. Patients may say their legs ‘feel funny’ or are ‘clumsy’ (uncoordinated). Initially, symptoms usually include paraesthesia — which means abnormal sensations, typically tingling or pricking (‘pins and needles’), in the hands, arms, legs or feet, and which can also occur in other parts of the body. This may be caused by damage to the peripheral sensory nerves (nerves responsible for transmitting sensations, such as pain and touch, to the brain) and can progress to numbness. Damage may also involve nerves that are responsible for controlling muscles, leading to muscle weakness, loss of balance and difficulty in walking. Reflex responses may be decreased or absent. The damage can involve both the peripheral nervous system and central nervous system, especially the spinal cord. Some cases involve urinary incontinence or retention, constipation and sexual dysfunction. Damage may progress to an inability to walk. In rare cases, the damage is severe enough to cause paraplegia (paralysis of the lower body and legs).

Many of the cases reported to poison centres from 2017 onwards involve neurotoxicity of varying severity. For example, in France during 2020, 58 % (n = 73) of 126 cases had sensory or motor problems, particularly paraesthesia but also problems with balance and walking. Most were in heavy users, who had been using the gas for periods ranging from a few weeks to several years. Use varied from 50 cartridges in an evening to more than 600 cartridges per day. Some reported using more than one 0.56 kg cylinder a day. Five were hospitalised for neurological issues. Meanwhile, in the Netherlands, 64 young adults were treated for a partial spinal cord injury caused by nitrous oxide use between 2018 and 2019.

Usually, the damage is at least partially reversible, especially if identified and treated early. Some individuals may be left with sensory or functional damage. Rare cases of permanent paralysis have been reported. Sometimes, patients stop treatment, so the long-term outcome is unknown.

There are no established treatment guidelines. Treatment involves stopping nitrous oxide use, supplementation with vitamin B12 and methionine, and supportive therapy including physiotherapy. However, studies are needed to identify the most effective treatments. If nitrous oxide use is not stopped, vitamin B12 supplementation may not prevent further damage or improve outcomes.

Prevalence

Information on the prevalence of nitrous oxide use in Europe is limited. Most general population surveys ask about volatile substance use, rather than nitrous oxide specifically. However, recent representative surveys have examined this issue in response to increased use in some countries, including France, Denmark and the Netherlands. Information is also available from England and Wales in the United Kingdom. Targeted surveys of clubbers, for example, typically find higher levels of regular use than in the general population.

In the Netherlands, the 2020 general population survey for adults aged 18 and older found that nitrous oxide use in the last 12 months was highest among young adults aged 18-19 years (14.5 %) and 20-24 years (12.1 %). This is six times higher than in the entire adult population (2.1 %). Meanwhile, use by 12- to 16-year-olds in the last 12 months was 6.7 %, with 11.7 % of 15- and 16-year-olds using the gas. In Denmark, a 2019 survey found that lifetime use in young people aged 15-25 years was 13.5 %, while 6.5 % used in the last 12 months. In France, a 2021 survey of students aged 14-15 found a 5.5 % reported lifetime use of the gas.

The level of use often varies within a country. For example, in Denmark, lifetime use was four times greater in the Copenhagen area than in North Jutland.

Separately, use in young people in England and Wales appears to have been established for a longer period than in other countries in Europe, with information on prevalence dating back to 2013. In that year, 7.6 % of those aged 16-24 years used in the last 12 months, while in 2019-20, 8.7 % reported using nitrous oxide in the last 12 months — equivalent to just over half a million people. This makes nitrous oxide the second most commonly used drug after cannabis, with use in that age group 3.5 times higher than in the entire adult population (2.4 %). Use had remained at the same level for the previous four years.

Typically, surveys find that more males than females use the gas, with some estimates suggesting the rate is around 30 to 50 % higher.

Nitrous oxide is typically used with friends, but it may also be used alone, especially with heavier use. It is used in a range of settings, including outside in public spaces (such as parks), in parked cars (so-called car parties), at home, at private parties, in nightclubs and at music concerts and festivals.

In some areas, the use of nitrous oxide outside has raised concerns over littering from discarded used cartridges and balloons. Noise nuisance has also been highlighted; this may be from the hissing sound from the release of gas from a cylinder and from a relatively large number of people gathering. These issues can have social, environmental and financial impacts — for example, the costs associated with cleaning up, while loud gatherings may intimidate some people.

Availability and supply

The availability and supply of the nitrous oxide used recreationally in Europe is not well understood, nor is the size and scale of the market.

Much of the gas is sourced from the small 8-gram cartridges that are used to make whipped cream. These can be bought from shops on the high street, such as supermarkets, convenience stores (night shops) and kiosks, as well as online. In France, the increased availability of nitrous oxide from 2017 coincided with the sale of cartridges in convenience stores, bars and nightclubs. In Denmark, until recent legislation, cartridges were sold in boxes of 10-100 in kiosks. It is unlikely that this is solely for making whipped cream.

Larger cylinders, also intended for food preparation, can be purchased from legitimate suppliers, although some companies may limit sales to registered businesses. Medicinal nitrous oxide is a prescription-only medicine, normally only administered by health care professionals.

Other companies specifically supply nitrous oxide to the recreational market. Some do this under the guise of supplying for culinary uses, typically whipped cream. The source of the nitrous oxide is unclear, but in some cases it appears that it was intended for food preparation.

In the Netherlands, suppliers openly advertise and promote the gas for recreational use, describing it with terms such as ‘laughing gas’ or ’party gas’. This includes distributing adverts through letterbox drops and handouts, as well as advertising online. They sell 8-gram cartridges, larger cylinders and related equipment, including crackers, balloons and fruit flavourings for them, and pressure regulators for larger cylinders. Some sell ‘starter packages’ of 10 cartridges with balloons and a cracker. Orders can be made online or by phone; payment is by card or cash. Delivery in discreet packaging can be on the same day (in some cases within 30 minutes) or the next day depending on location. Some sites offer delivery to other countries in Europe. A risk assessment in the Netherlands in 2019 found that there is some level of criminal involvement in the trade.

A recent innovation in the recreational market, since around 2017, is the sale of larger cylinders. These range from 0.58 to 15 kg, supplying almost 300 litres to just over 5 000 litres of the gas respectively. This has made the gas cheaper to use; it may also promote wider use, as well as more frequent and prolonged, heavy use (Table 1). The greater availability of cylinders may also promote riskier ways of using the gas and lead to more burns and lung injuries.

Table 1. Cylinder sizes and cost of nitrous oxide offered by retailers in the Netherlands. Volume of gas is calculated based on the density of gas 1.799 g/L at 25 °C and 1 bar (Haynes, 2014)

Cylinder size (kg)	Volume of gas (L)	Cylinder price (€)	Price per litre (€)	Number of balloons	Price per balloon (€)
0.008	4	0.50	0.13	1	0.50
0.58	322	28	0.09	80	0.35
2	1 112	40	0.04	278	0.14
10	5 559	160	0.03	1 390	0.12

The 0.58 and 2 kg cylinders appear to be the most popular with users. Of particular note are the 0.58 kg cylinders that contain more than 300 litres of the gas. This is sufficient for around 80 balloons and is 25 % cheaper than using ‘traditional’ 8-gram cartridges. The cylinders are relatively discreet and portable, providing an ‘all in one’ solution for filling large numbers of balloons rapidly. The balloon is placed over the nozzle, and turning the nozzle opens the gas valve, allowing the required volume to be dispensed (Figure 3). In addition, unlike larger cylinders, the 0.58 kg cylinders are disposable and retailers do not require a security deposit, making them more attractive to younger users. During 2022, retailers have introduced similar disposable 2 kg cylinders.

Figure 3. Disposable 0.58 kg nitrous oxide cylinders discarded in the street – Liverpool, United Kingdom, September 2022. Photos were taken on a Sunday morning and presumably discarded after being used on the previous Saturday night

Source: Michael Evans-Brown and Harry Evans-Brown.

Two large-scale seizures involving such cylinders have recently been reported by police in France. In December 2021, seven tonnes were seized (3.5 million litres), while in August 2022, almost 15 tonnes were seized (7.6 million litres).

In the Netherlands and the United Kingdom, at least, the financial interests of those selling nitrous oxide for recreational use appear to play an important role in promoting the use of the gas.

In addition, illicit markets have developed in some countries, with ‘street-level dealers’ selling nitrous oxide. Social media is also used to promote and sell the gas. In some cases, the supply has moved from shops to social media following measures to restrict the supply of the gas.

The social supply of the gas between friends and other close social networks also plays an essential role in the distribution of the gas.

The safety and quality of nitrous oxide products inhaled for recreational use in Europe has not been assessed. In most cases, sellers use products intended for food preparation. Those supplying the recreational market claim it is ‘food grade’ or ‘medical grade’, although these claims have not been checked. Food grade nitrous oxide is not intended to be inhaled. Concerns from the possible presence of oils used as coatings or lubricants during the manufacture of cartridges have been noted. As has the potential risk of met-al particles breaking off from cartridges when they are opened, which could be inhaled. Such injuries have not been reported to date.

COVID-19 pandemic

The effect of the COVID-19 pandemic on nitrous oxide use is unclear. When lockdown measures closed nightlife venues, use may have reduced in some people attending these venues. Conversely, it appears that some users started to use nitrous oxide more frequently at home. Possible reasons for this include disruptions to the illicit drug market as well as boredom, anxiety, and stress experienced during the pandemic. The ease of availability from bricks and mortar shops and online suppliers may be linked to this. Home delivery despite the lockdown measures appeared to have played an important role in maintaining or increasing use in some cases. A report from French Poison Centres notes that many of the 134 cases during 2020 started or increased their use during the first lockdown, as it was easy to buy and get delivered.

Pharmacology

How nitrous oxide produces its effects is complex and not fully understood. The gas affects several networks in the central nervous system (brain and spinal cord), such as those regulating pain, perception, anxiety, mood and emotion, behaviour, and reward. These involve glutamate, opioid, noradrenaline, and γ-aminobutyric acid (GABA) neurotransmitters, among others. Importantly, some effects from the recreational use of nitrous oxide arise from hypoxia caused by inhaling the gas and displacement of oxygen — unlike medical nitrous oxide, which is always given as a mixture with oxygen. Nitrous oxide is not metabolised (broken down) by the body, but instead exhaled un-changed by the lungs.

Many of the major effects of nitrous oxide, such as analgesia, anaesthesia, dissociation, as well as reward and behavioural effects, appear to include blocking the actions of the N-methyl-D-aspartate (NMDA) glutamate receptor. This receptor is involved in many processes that modify sensations and perceptions of pain, euphoria, and the effects of dissociative anaesthetics in general.

The analgesic effects of nitrous oxide are also believed to involve the opioid system, including the endorphins. The gas causes their release in certain brain regions, which in turn activates other neurotransmitter pathways, including noradrenaline, that is thought to reduce the reception of pain messages originating from the body.

The anxiolytic effect of nitrous oxide has some similarities with those induced by benzodiazepines, and likely involves activation of the gamma-aminobutyric acid type A (GABAA) receptor through the benzodiazepine binding site, which has a calming effect on many parts of the brain.

The abuse liability and dependence potential of nitrous oxide is not well understood. The gas does have reinforcing properties, which may involve blocking the NMDA receptor. Some users engage in frequent and heavy use, which meets the criteria for sub-stance dependence and substance use disorder. Despite limited understanding of the mechanisms, some users may develop drug dependence and problematic use. The short-lived effects of the gas are often cited as a reason for repeated use in the same session.

Legitimate uses

Nitrous oxide has important, wide-ranging, medical, industrial, commercial, and scientific uses. It is widely used as an analgesic and anaesthetic in medicine. The gas is classed as a dissociative anaesthetic, with the World Health Organization listing it as an essential medicine. It is a prescription-only medicine, administered by inhalation. Mixed with oxygen, nitrous oxide is used for short-term pain relief and to reduce anxiety during childbirth, dental procedures, emergency treatment of injuries, and as part of end-of-life care. It is also used as a surgical anaesthetic.

Nitrous oxide is also extensively used as a food additive, and particularly as an aerosol propellant used to make whipped cream. It is also used as a refrigerant, leak detecting agent, oxidising agent, chemical reagent, in semiconductor manufacturing, and to make electrical, electronic, and optical equipment, as well as an additive to fuels in car racing.

Environmental concerns

Littering of used cartridges, balloons, and cylinders has been highlighted as an issue in some areas. The cartridges and cylinders are steel, which can be recycled. Used cylinders pose a risk of explosion during waste processing if discarded in general waste. Discarded balloons break down slowly in the environment and can be eaten by wildlife, who can suffocate.

Nitrous oxide is a potent greenhouse gas: 300 times more powerful than carbon dioxide. It is also a major cause of the destruction of the ozone layer. Global emissions of the gas are increasing as a result of human activities that stimulate its production, especially large-scale farming with synthetic fertilisers and cattle ranching. It is the third most important greenhouse gas, after carbon dioxide and methane. Currently, the impact from increased recreational use on the environment is unknown. While its contribution is minor compared to other sources, as nitrous oxide is exhaled unchanged from the lungs into the atmosphere, the environmental impact requires research.

Responses

This final part examines some of the response measures taken to reduce the availability, use and harms, caused by nitrous oxide.

The use of a substance in a new geographical area or new groups of users is always a cause of concern for public health. This is because the population will have little or no experience with its effects and how to use it. Similar concerns apply to new ways of using a substance, new products, or new patterns of use. While some risks might be known, others are unknown, and some are unknowable until larger numbers of people have been exposed to the substance. These issues all apply to the increased recreational use of nitrous oxide seen in some parts of Europe, especially since 2017.

Developing and implementing responses to nitrous oxide, whether at EU, national, local or individual level, involves three basic steps:

1. Identify the nature of the problems to be addressed.
2. Select potentially effective interventions to tackle these problems.
3. Implement, monitor and evaluate the impact of these interventions.

General information on these steps, and advice for designing, targeting and implementing effective responses, are available in the EMCDDA’s publication: Health and social responses to drug problems: A European guide.

Nitrous oxide can be considered as a new psychoactive substance. However, its widespread legitimate uses and availability, makes monitoring it through the Early Warning System difficult. In addition, its use as a medicine precludes risk assessment at EU level. No guidelines on responses exist at European level.

Countries experiencing issues with nitrous oxide have typically strengthened monitoring in order to better understand the nature of the problem and the risks. This includes studying the prevalence and use in the general population and ‘at risk’ user groups, as well as their perspectives. It also includes studying the markets and harms.

In some cases, formal risk assessment to identify, describe, and estimate the magnitude of the public health and social risks from nitrous oxide has been used to inform the type of responses that are likely to be most effective. In addition, continued monitoring of the situation and evaluation of response measures has been used to inform the need for changes to the existing approach as well as additional responses.

Monitoring systems, including early warning systems, may need to be developed or adapted to monitor nitrous oxide use and harms. Standardised case definitions and classification systems may need to be developed. Better clinical coding is also needed. This allows better diagnosis and treatment, as well as understanding and quantification of the issue. It also allows the number of cases or rate of events identified in one time or place to be compared with the number or rate from another time or place.

Poison centres, hospital emergency departments, specialist neurology and burns centres, and the police all play a key role in identifying, monitoring, and responding to the increase in harms caused by nitrous oxide. As do outreach and street-work agencies, and drug prevention and harm reduction services. Working with these agencies as well as people who use nitrous oxide helps understand use and harms, and inform development of effective responses.

It is important to recognise that the vast majority of people do not use nitrous oxide. Those that do typically use relatively small amounts infrequently. Use may also vary significantly within a country. Most use of nitrous oxide is by young people, including teenagers. It is important to avoid normalising and unintentionally promoting its use. Therefore, targeted and environmental interventions should be considered rather than general information or warning campaigns.

Targeted health promotion, including risk communication, should provide timely, clear, credible, and consistent evidence-based messages that raise awareness, understanding, and practical actions that can be taken. This may include communications with users as well as parents and guardians, and should come from trusted sources.

Simple, evidence-based, harm reduction advice may help prevent both common adverse effects and the more serious risks linked to nitrous oxide. It can also be used to inform people what to do in an emergency, and how to seek additional information and help. Existing resources commonly:

• Explain what the gas is, how it is used, its effects, unwanted adverse effects, and other risks;
• Explain why inhaling from a balloon, rather than a cartridge or cylinder, reduces the risk of burns, lung injuries, and asphyxiation;
• Advise that people sit in a safe environment before inhaling the gas, as this helps prevent injuries from falls caused by fainting or loss of co-ordination and balance while intoxicated;
• Highlight the dangers of driving, or riding a bike or scooter, while intoxicated. The apparent perception that you can drive safely while using the gas may also need to be addressed;
• Highlight the dangers of using other drugs, including alcohol, at the same time;
• Explain the need for urgent medical care for burns;
• Highlight the risks of chronic toxicity from frequent and heavy use; especially important are messages on identifying the early signs of nerve damage and the need to obtain medical care as soon a possible;
• Advise what to do in an emergency;
• Direct people to further information, treatment, and services.

In addition, awareness and understanding of the issue, as well as evidence-based training materials for healthcare professionals, drug workers, social workers, and the police may need to be developed.

Any response to nitrous oxide needs to consider the widespread legitimate uses of the gas by industry, healthcare, and consumers. Currently, there are few, if any, alternatives to the gas for these uses. Awareness of this issue, discussions, and consultation will be required with these partners.

In some countries, the availability of nitrous oxide to consumers has been restricted. Although this may be an approach to limiting availability and use, the impact of these measures needs to be carefully monitored to assess their effectiveness and avoid the risk of unintended negative consequences.

Responses taken include:

• Restricting the maximum quantity of cartridges that can be supplied at any one time;
• Age-restricted sales, typically to those aged 18 and over. Require the display of a notice on premises that details the offence of selling to under 18s. Requiring age verification in both bricks and mortar shops and online;
• Restricting sales of nitrous oxide products during the night (such as between 10pm and 5am). This may include online sales too;
• Preventing nitrous oxide products being visible or accessible to the public in retail stores;
• Prohibiting the sale of nitrous oxide by bars and clubs. In addition, sales have been banned in shops selling alcohol, tobacco products, or electronic cigarettes;
• Requiring warning labels on nitrous oxide products. This includes the 8-gram cartridges that are the most common source of the gas. Warnings may also provide contact details for poison centres;
• Requiring record keeping of sales to verify legal sales have been implemented;
• Prohibiting sale of crackers and balloons when intended to be used with nitrous;
• Strengthening legislation around safe transport and storage of nitrous oxide

In some cases, existing legislation and voluntary measures may help reduce the availability and harmful use of the gas for recreational use.

This may include EU and national legislation, such as the REACH and CLP Regulations that require appropriate labelling and packaging of nitrous oxide products, including their hazards. It may also include food additive legislation and consumer protection and product safety legislation. Separately, medicines containing nitrous oxide are regulated under medicines legislation and are classed as prescription-only medicines.

Most recreational use is from 8-gram cartridges. These are typically associated with relatively low levels of use and limited harms. Restricting the availability of these cartridges may cause a switch to larger volume cylinders. This may lead to overall greater levels of harms from more frequent and heavy use, burns, and risk of asphyxiation. The recent introduction of disposable larger cylinders to the recreational market highlights this potential. As such, some countries have restricted the sale of cylinders to consumers. Simultaneously, measures to prevent diversion and theft of cylinders from the legitimate supply chain, as well as healthcare facilities and other sites, such as restaurants, have also been taken.

Similarly, the substitution with more harmful drugs, including those that are more readily available to this age group, especially teenagers, should be considered. These may include deodorants, spray paints, or other sources of volatile substances.

Responses should also consider how some retailers currently exploit existing legislation (loopholes). One particular issue dating back to the 1970s is selling the gas under the guise of being used to make whipped cream.

In the United Kingdom, prohibiting the sale of nitrous oxide for recreational use appears to have had no impact on prevalence, which has remained stable and at higher levels for almost a decade. Recently, and similar to other counties, larger cylinders, such as the 0.58 kg cylinders, are also sold on the recreational market.

In some countries, the market for recreational nitrous oxide is lucrative. This appears to play an important part in driving its availability and ‘innovations’ such as larger cylinders.

Restricting supply may lead to involvement of criminal organisations. This may increase theft and diversion from the legitimate supply chain. It may also lead to homemade or illicit production of nitrous oxide. Methods on the internet, including do-it-yourself videos, pose a high risk of explosion and contamination with nitrogen oxides that cause lung toxicity, which could be life-threatening.

Many of the chronic effects caused by nitrous oxide are linked to the irreversible inactivation of vitamin B12. More people, particularly young people, are choosing vegetarian and vegan diets that are poor in this vitamin. Low-levels of the vitamin increases the risk of chronic toxicity, particularly nerve damage. Due to this, the level of vitamin B 12 deficiencies in this group and risk of chronic toxicity may need to be assessed. Supplementation with vitamin B12 while continuing to use nitrous oxide does not appear to stop chronic toxicity.

Littering of used cartridges, balloons, and cylinders has been highlighted as an issue in some areas. Importantly, canisters and cylinders are steel which can be recycled; although not all areas recycle steel. Evidence-based interventions to reduce littering exist, although their application to nitrous oxide litter will need to be assessed. Among other factors, interventions that motivate a sense of responsibility to the community may help.

Finally, our understanding of the use, harms, and effective responses are limited, partly because this level of recreational use is relatively new. Research is needed in areas such as epidemiology, supply, pharmacology, toxicology, as well as the effectiveness of treatments and response measures.

Further resources

• Read the full report: 'Recreational use of nitrous oxide — a growing concern for Europe'
• 25 years of early warning and response to new psychoactive substances in Europe

Source tables

Source table for Figure 1: Number of reports related to serious harms involving nitrous oxide use in the PubMed database, 1978–2022 (August). Increased awareness of the chronic harms of nitrous oxide may have contributed to this increase

Year	Number of case reports
1978	5
1979	2
1980	1
1981	1
1982	2
1983	3
1984	1
1985	1
1986	1
1988	3
1989	1
1991	1
1992	1
1995	1
1996	1
1997	2
1998	2
2000	1
2001	2
2003	2
2004	2
2005	1
2006	2
2007	5
2008	1
2009	1
2010	3
2011	6
2012	3
2013	6
2014	4
2015	6
2016	5
2017	8
2018	15
2019	17
2020	22
2021	29
2022	15