Nitrous oxide

• 1. Introduction

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  Nitrous oxide, also called dinitrogen oxide, dinitrogen monoxide, laughing gas or simply nitrous, is a colourless gas with a faint, slightly sweet scent and taste. By 2020, every billion molecules of air held 333 of its molecules, and that number keeps climbing. The same compound sits in dentists' surgeries, racing engines and cans of whipped cream. How did a gas that makes people giggle become a medicine, a fuel additive and a pantry ingredient? Why did it take decades for doctors to trust it against pain? And why do climate scientists now treat this sweet-smelling vapour as a problem worth tracking year by year?

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• 2. Factitious Airs

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  In 1772, the English natural philosopher and chemist Joseph Priestley made the gas for the first time. He called it dephlogisticated nitrous air, or sometimes inflammable nitrous air, names that belong to the old phlogiston theory of burning. He described his recipe in the book Experiments and Observations on Different Kinds of Air, published in 1775. Iron filings, dampened with nitric acid, were heated to produce what he called nitrous air diminished.

  Two decades later, Thomas Beddoes and James Watt joined forces on a 1794 book titled Considerations on the Medical Use and on the Production of Factitious Airs. Watt had invented a machine for making these artificial airs, nitrous oxide among them, along with a breathing apparatus to inhale them. His machine had three parts. A furnace burned the starting material, a water vessel with a spiral pipe washed impurities from the gas, and a gasometer filled portable bags made of airtight oily silk. The breathing apparatus was simply one of those bags joined by a tube to a mouthpiece. Beddoes supplied the medical theory, which held that tuberculosis and other lung diseases could be treated by inhaling such airs.

  In 1798 Beddoes founded the Pneumatic Institution for Relieving Diseases by Medical Airs in Hotwells, Bristol. In the basement, a large machine produced gases under the supervision of a young Humphry Davy. Davy was encouraged to experiment with new gases for patients to inhale, and nitrous oxide became his first important project. He published his findings in Researches, Chemical and Philosophical in 1800. On page 465 he noted the gas's pain-relieving effect, and on page 556 he suggested it might be used in surgical operations. Davy also coined the name laughing gas.

  Beginning in 1799, laughing gas parties became an immediate success, mainly among the British upper class. The gas generally left users looking stuporous, dreamy and sedated, though some got the giggles and erupted in laughter. One of the earliest commercial producers in the United States was George Poe, cousin of the poet Edgar Allan Poe, who was also the first to liquefy the gas. Even so, after Davy's discovery that the gas could relieve a conscious person of pain, another 44 years passed before doctors tried it for anaesthesia.

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• 3. The Dentist's Gamble

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  On the 11th of December 1844, the dentist Horace Wells, assisted by Gardner Quincy Colton and John Mankey Riggs, showed that a patient could feel no pain during a dental extraction. In the following weeks Wells treated the first 12 to 15 patients with the gas in Hartford, Connecticut. By his own record, he failed in only two cases. He reported these results to the medical society in Boston in December 1844.

  Yet in January 1845, Wells gave his first public demonstration to the medical faculty in Boston, and it was partly unsuccessful. His colleagues came away doubtful about its efficacy and safety. That failure is most likely why other dentists did not adopt the method at once. Not until 1863 did it come into general use, when Colton began using it in all of his Colton Dental Association clinics, newly established in New Haven and New York City. Over the following three years, Colton and his associates gave nitrous oxide to more than 25,000 patients.

  Colton's success drew in less reputable operators. Quacksalvers touted the gas as a cure for consumption, scrofula, catarrh and other diseases of the blood, throat and lungs. C. L. Blood and Jerome Harris in Boston, and Charles E. Barney of Chicago, administered and licensed nitrous oxide treatment as a patent medicine.

  Surgeons wanted something stronger, because nitrous oxide proved too weak for major operations in hospitals. Diethyl ether, a more potent anaesthetic, was demonstrated and accepted in October 1846, and chloroform followed in 1847. Then, in 1876, Joseph Thomas Clover invented the gas-ether inhaler, which supplied nitrous oxide and ether together. The operator controlled the exact mixture. Hospitals began every anaesthetic with a mild flow of nitrous oxide and gradually increased the dose of ether or chloroform. Many kept using Clover's device until the 1930s, and today's machines still follow the same principle.

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• 4. How It Eases Pain

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  Modern hospitals deliver nitrous oxide through an automated relative analgesia machine. It pairs an anaesthetic vaporiser with a medical ventilator and supplies a breath-actuated flow of nitrous oxide mixed with oxygen in a 2:1 ratio. The gas is a weak general anaesthetic, so it is rarely used alone. It serves instead as a carrier gas, mixed with oxygen, for stronger drugs such as sevoflurane or desflurane. Its minimum alveolar concentration is 105 percent and its blood/gas partition coefficient is 0.46. Using it in anaesthesia can raise the risk of postoperative nausea and vomiting.

  Dentists use a simpler machine that delivers only a gas and oxygen mixture. It must be a recognised, purpose-designed relative analgesic flowmeter, with at least 30 percent oxygen at all times and no more than 70 percent nitrous oxide. The patient stays conscious and can answer the dentist's questions and instructions. In dentistry the gas works as an anxiolytic, an adjunct to local anaesthetic.

  Beyond the dental chair, inhaled nitrous oxide is used frequently to relieve pain from childbirth, trauma, oral surgery and acute coronary syndrome, which includes heart attacks. Its use during labour has been shown to be safe and effective, while its benefit for acute coronary syndrome is unknown. In Canada and the UK, ambulance crews commonly carry Entonox and Nitronox as rapid analgesic gas. A 50 percent mixture can even be considered for trained non-professional first aid responders. Its effect reverses quickly, so it would not stand in the way of diagnosis.

  How the gas does all this is still not fully known. It acts on a broad range of ligand-gated ion channels. It moderately blocks NMDA receptors, weakly inhibits several other receptor types and slightly boosts GABA and glycine receptors. Its anaesthetic, hallucinogenic and euphoric effects probably come mainly from blocking NMDA receptor currents. The gas is also 30 to 40 times more soluble than nitrogen.

  Its calming effect looks tied to GABA receptors. Animals that have grown tolerant to the anti-anxiety effects of benzodiazepines are partly tolerant to nitrous oxide too. In people given a 30 percent dose, drugs that block benzodiazepine receptors reduced reports of feeling high but did not change psychomotor performance.

  The pain relief runs through a different route, linking the body's own opioid system to noradrenergic neurons that descend toward the spine. Animals made tolerant to morphine are also tolerant to the gas's pain-reducing effect. The leading idea is that the gas triggers release of endogenous opioids, which frees brainstem noradrenergic neurons to release norepinephrine into the spinal cord and dampen pain signals. Exactly how the gas prompts that opioid release remains uncertain.

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• 5. Fuel and Froth

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  In a 1914 patent, the American rocket pioneer Robert Goddard proposed nitrous oxide and gasoline as possible propellants for a liquid-fuelled rocket. At elevated temperatures the gas acts as a powerful oxidiser, much like molecular oxygen. Compared with other oxidisers it is far less toxic and more stable at room temperature, which makes it easier to store and safer to carry on a flight. SpaceShipOne and other hybrid rockets have paired it with hydroxyl-terminated polybutadiene fuel, and amateur rocketeers pair it with various plastics.

  At a heated catalyst temperature of 577 C, the gas can also decompose by itself into nitrogen and oxygen, working as a monopropellant. In a vacuum thruster this can reach a specific impulse of up to 180 seconds. That falls well short of hydrazine thrusters, but the lower toxicity makes it a worthwhile option. Ignition depends sharply on pressure. At 600 C and 309 psi, or 21 atmospheres, ignition takes only 6 joules. At 130 psi, even 2,500 joules is not enough.

  In motor racing, nitrous oxide boosts engine power by supplying extra oxygen, so the engine can burn more fuel. Stored as a compressed liquid, it evaporates in the intake manifold, and the expansion sharply cools the charge. A denser charge lets more air and fuel enter the cylinder. During World War II, the Luftwaffe used a system called GM-1 to boost aircraft engines at extreme altitude. Only specialised planes carried it, such as high-altitude reconnaissance aircraft, high-speed bombers and interceptors. Some also carried MW 50, a water and methanol injection system.

  The danger for engines is pressure more than raw power, since the gas packs a much denser charge into the cylinder. The extra pressure and heat can melt, crack or warp the piston, valve and cylinder head. Automotive-grade nitrous oxide differs slightly from the medical kind, because a small amount of sulfur dioxide is added to discourage abuse.

  In the kitchen, the gas carries the food additive code E942 and serves as an aerosol propellant. In a pressurised whipped cream canister it dissolves in the fatty cream until the cream leaves the can. There it turns to gas and forms foam, producing whipped cream four times the volume of the liquid, where whipping in air yields only twice the volume. Carbon dioxide cannot do the job, because it is acidic in water and would curdle the cream. Unlike air, nitrous oxide also slows rancidification of the butterfat. The extra-frothed cream is unstable, though, and returns to liquid within half an hour to an hour. Some cooking sprays, made from oils with lecithin as an emulsifier, use the gas too, while others use food-grade alcohol or propane.

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• 6. Party Gas

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  In the UK in 2014, almost half a million young people were estimated to use nitrous oxide at nightspots, festivals and parties. From the 19th century onward, wide availability for medical and culinary purposes let recreational use expand across the globe. The 2017 Vice documentary Inside The Laughing Gas Black Market followed journalist Matt Shea as he met dealers who stole the gas from hospitals. In London, press coverage has focused on discarded canisters, whose litter is highly visible and draws many complaints from communities.

  Law has struggled to keep up. In August 2015, the Council of the London Borough of Lambeth banned recreational use, with on-the-spot fines of up to £1,000. The Psychoactive Substances Act 2016 made it illegal to produce, supply, import or export the gas for recreational use. In September 2023, the UK Government announced a tougher step. From the 8th of November 2023, possession became illegal too, and the gas became a Class C drug under the Misuse of Drugs Act 1971. Possession can carry up to two years in prison or an unlimited fine.

  Other places draw the line differently. In Australia, recreational use became a public health concern after a rise in reports of neurotoxicity and emergency room admissions, and South Australia passed legislation in 2020 to restrict canister sales. The New Zealand Ministry of Health warns that the gas is a prescription medicine under the Medicines Act. Possession is legal under United States federal law and outside DEA purview, but the Food and Drug Administration can pursue misbranding charges for sale meant for human use. In California, recreational possession is a misdemeanor. In India, moving the gas from bulk cylinders into smaller E-type tanks of 1,590 litres is legal when intended for medical anaesthesia.

  In 2024, under the street name Galaxy Gas, nitrous oxide exploded in popularity among young people, partly driven by TikTok trends.

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• 7. Hidden Hazards

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  Heavy users, meaning 400 grams or 200 litres of gas in one session, and frequent users, meaning daily or weekly, have reported signs of peripheral neuropathy to poison control centers. These include ataxia, a change in gait, and paresthesia, such as tingling or numbness in the limbs. Whipped-cream chargers, nicknamed whippits or nangs, contain no oxygen, so extended use can also cause neurological harm through hypoxia. Inhaling pure gas, as with a strap-on mask or prolonged breath-holding, can deprive the body of oxygen. The result can be low blood pressure, fainting and even heart attacks.

  The deeper chemical culprit is vitamin B12. The gas inactivates the cobalamin form of the vitamin by oxidation. People with a hidden deficiency can develop sensory neuropathy, myelopathy and encephalopathy within days or weeks of nitrous oxide anaesthesia. High doses of B12 treat the symptoms, but recovery can be slow and incomplete. People with normal levels have enough stores that a single exposure is insignificant, unless use is repeated and prolonged. For that reason, anyone with risk factors for deficiency should have B12 levels checked before anaesthesia.

  Hospital staff face their own exposure. Humans metabolise only 0.004 percent of the gas, so a patient exhales nearly all of it into the room. In a poorly ventilated clinic, surgeons, dentists and nurses can be intoxicated and face chronic exposure. The National Institute for Occupational Safety and Health set a recommended exposure limit of 25 ppm, or 46 mg/m3, for escaped anaesthetic. Occupational exposure has been linked to DNA damage, though the link depends on dose and does not appear to extend to casual recreational use. Studies in rats also suggest that chronic exposure of pregnant females may harm the developing fetus.

  In rodents, prolonged exposure over several hours is believed to produce Olney's lesions, as other NMDA receptor antagonists do. Because the gas leaves the body quickly, it is less likely to be neurotoxic than those drugs. A rodent model even hints at a possible role in treating stroke, where 75 percent gas by volume reduced neuronal death after blockage of the middle cerebral artery.

  The physical hazards are just as real. Industrial makers heat ammonium nitrate to about 250 C, and the reaction can be hard to control, sometimes ending in detonation. At 20 C the saturated vapour pressure is 50.525 bar, rising to 72.45 bar at the critical temperature of 36.4 C. Contaminated parts have been implicated in rocketry accidents, where small fuel and gas mixtures explode with a water-hammer effect called dieseling. Stainless steel and aluminium can act as fuels beside such a strong oxidiser, and decomposition in plumbing has even blown up large tanks.

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• 8. Atmospheric Footprint

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  From a base level of about 270 ppb in 1750, nitrous oxide has risen by more than 20 percent, reaching 339 ppb in 2025. The growth rate of about 1 ppb per year has also accelerated in recent decades. The IPCC reported in 2022 that synthetic fertilizers, manure, farming and fossil fuel burning drove the 31.0 ppb rise, about 10 percent, between 1980 and 2019.

  The gas ranks as the third most important greenhouse gas, with a 100-year global warming potential of 273 times that of carbon dioxide and an atmospheric lifetime of 116 years, give or take 9. Humans emit an amount with a greenhouse effect of about 3 billion tonnes of carbon dioxide each year. For comparison, humans emitted 37 billion tonnes of actual carbon dioxide in 2019, and methane equal to 9 billion tonnes. It also thins the ozone layer, with an ozone depletion potential of 0.017 against 1 for CCl3F. A 2009 study named it the single most important ozone-depleting emission, expected to stay the largest through the 21st century.

  About 40 percent of the 17.0 million tonnes of nitrogen emitted each year in 2007-2016 came from people. Soils under natural vegetation account for 60 percent of natural emissions, the oceans for 35 percent and atmospheric chemical reactions for 5 percent. Microorganisms such as denitrifying bacteria and fungi make most of it. Among human sources, fertilised soils and livestock manure supply 42 percent, and fertiliser runoff and leaching 25 percent. Biomass burning and fossil fuel combustion with industry each add 10 percent, the breakdown of other nitrogen emissions adds 9 percent and human sewage adds 5 percent. Nitric acid and adipic acid production are the largest industrial sources. Adipic acid is a precursor to nylon and other synthetic fibres.

  The gas may also have played a part in the past. A rise in atmospheric nitrous oxide has been implicated as a possible contributor to the extremely intense warming of the Cenomanian-Turonian boundary event. Measuring today's emissions from soil is hard, because they vary markedly across time and space. The majority of a year's emissions may occur in short "hot moments" and at particular "hotspots".

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