Laughing gas, sweet air, protoxide of nitrogen, hyponitrous oxide, dinitrogen oxide, dinitrogen monoxide
3D model (JSmol)
|UN number||1070 (compressed)|
|Molar mass||44.013 g/mol|
|Density||1.977 g/L (gas)|
|Melting point||−90.86 °C (−131.55 °F; 182.29 K)|
|Boiling point||−88.48 °C (−127.26 °F; 184.67 K)|
|1.5 g/L (15 °C)|
|Solubility||soluble in alcohol, ether, sulfuric acid|
|Vapor pressure||5150 kPa (20 °C)|
Refractive index (nD)
|1.000516 (0 °C, 101,325 kPa)|
Std enthalpy of
|1=ATC code }}||N01AX13 (WHO)|
|Safety data sheet||Ilo.org, ICSC 0067|
|NFPA 704 (fire diamond)|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|what is ?)(|
Nitrous oxide, commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula N2O. At room temperature, it is a colourless non-flammable gas, and has a slightly sweet scent and taste. At elevated temperatures, nitrous oxide is a powerful oxidiser similar to molecular oxygen.
Nitrous oxide has significant medical uses, especially in surgery and dentistry, for its anaesthetic and pain reducing effects. Its colloquial name, "laughing gas", coined by Humphry Davy, is due to the euphoric effects upon inhaling it, a property that has led to its recreational use as a dissociative anaesthetic. It is on the World Health Organization's List of Essential Medicines. It is also used as an oxidiser in rocket propellants, and in motor racing to increase the power output of engines.
Nitrous oxide's atmospheric concentration reached 333 parts per billion (ppb) in 2020, increasing at a rate of about 1 ppb annually. It is a major scavenger of stratospheric ozone, with an impact comparable to that of CFCs. Global accounting of N2O sources and sinks over the decade ending 2016 indicates that about 40% of the average 17 TgN/yr (Teragrams of Nitrogen per year) of emissions originated from human activity, and shows that emissions growth chiefly came from expanding agriculture and industry sources within emerging economies. Being the third most important long-lived greenhouse gas, nitrous oxide also substantially contributes to global warming.
Nitrous oxide may be used as an oxidiser in a rocket motor. It has advantages over other oxidisers in that it is much less toxic, and because of its stability at room temperature it is also easier to store and relatively safe to carry on a flight. As a secondary benefit, it may be decomposed readily to form breathing air. Its high density and low storage pressure (when maintained at low temperature) enable it to be highly competitive with stored high-pressure gas systems.
In a 1914 patent, American rocket pioneer Robert Goddard suggested nitrous oxide and gasoline as possible propellants for a liquid-fuelled rocket. Nitrous oxide has been the oxidiser of choice in several hybrid rocket designs (using solid fuel with a liquid or gaseous oxidiser). The combination of nitrous oxide with hydroxyl-terminated polybutadiene fuel has been used by SpaceShipOne and others. It also is notably used in amateur and high power rocketry with various plastics as the fuel.
Nitrous oxide also may be used in a monopropellant rocket. In the presence of a heated catalyst, N2O will decompose exothermically into nitrogen and oxygen, at a temperature of approximately 1,070 °F (577 °C). Because of the large heat release, the catalytic action rapidly becomes secondary, as thermal autodecomposition becomes dominant. In a vacuum thruster, this may provide a monopropellant specific impulse (Isp) of as much as 180 s. While noticeably less than the Isp available from hydrazine thrusters (monopropellant or bipropellant with dinitrogen tetroxide), the decreased toxicity makes nitrous oxide an option worth investigating.
Nitrous oxide is said to deflagrate at approximately 600 °C (1,112 °F) at a pressure of 309 psi (21 atmospheres). At 600 psi, for example, the required ignition energy is only 6 joules, whereas N2O at 130 psi a 2,500-joule ignition energy input is insufficient.
Internal combustion engine
In vehicle racing, nitrous oxide (often referred to as just "nitrous") allows the engine to burn more fuel by providing more oxygen during combustion. The increase in oxygen allows for an increase in the injection of fuel, allowing the engine to produce more engine power. The gas is not flammable at a low pressure/temperature, but it delivers more oxygen than atmospheric air by breaking down at elevated temperatures, about 570 degrees F (~300C). Therefore, it often is mixed with another fuel that is easier to deflagrate. Nitrous oxide is a strong oxidising agent, roughly equivalent to hydrogen peroxide, and much stronger than oxygen gas.
Nitrous oxide is stored as a compressed liquid; the evaporation and expansion of liquid nitrous oxide in the intake manifold causes a large drop in intake charge temperature, resulting in a denser charge, further allowing more air/fuel mixture to enter the cylinder. Sometimes nitrous oxide is injected into (or prior to) the intake manifold, whereas other systems directly inject, right before the cylinder (direct port injection) to increase power.
The technique was used during World War II by Luftwaffe aircraft with the GM-1 system to boost the power output of aircraft engines. Originally meant to provide the Luftwaffe standard aircraft with superior high-altitude performance, technological considerations limited its use to extremely high altitudes. Accordingly, it was only used by specialised planes such as high-altitude reconnaissance aircraft, high-speed bombers and high-altitude interceptor aircraft. It sometimes could be found on Luftwaffe aircraft also fitted with another engine-boost system, MW 50, a form of water injection for aviation engines that used methanol for its boost capabilities.
One of the major problems of using nitrous oxide in a reciprocating engine is that it can produce enough power to damage or destroy the engine. Very large power increases are possible, and if the mechanical structure of the engine is not properly reinforced, the engine may be severely damaged, or destroyed, during this kind of operation. It is very important with nitrous oxide augmentation of petrol engines to maintain proper operating temperatures and fuel levels to prevent "pre-ignition", or "detonation" (sometimes referred to as "knock"). Most problems that are associated with nitrous oxide do not come from mechanical failure due to the power increases. Since nitrous oxide allows a much denser charge into the cylinder, it dramatically increases cylinder pressures. The increased pressure and temperature can cause problems such as melting the piston or valves. It also may crack or warp the piston or head and cause pre-ignition due to uneven heating.
Automotive-grade liquid nitrous oxide differs slightly from medical-grade nitrous oxide. A small amount of sulfur dioxide (SO2) is added to prevent substance abuse. Multiple washes through a base (such as sodium hydroxide) can remove this, decreasing the corrosive properties observed when SO2 is further oxidised during combustion into sulfuric acid, making emissions cleaner.
The gas is approved for use as a food additive (E number: E942), specifically as an aerosol spray propellant. Its most common uses in this context are in aerosol whipped cream canisters and cooking sprays.
The gas is extremely soluble in fatty compounds. In aerosol whipped cream, it is dissolved in the fatty cream until it leaves the can, when it becomes gaseous and thus creates foam. Used in this way, it produces whipped cream which is four times the volume of the liquid, whereas whipping air into cream only produces twice the volume. If air were used as a propellant, oxygen would accelerate rancidification of the butterfat, but nitrous oxide inhibits such degradation. Carbon dioxide cannot be used for whipped cream because it is acidic in water, which would curdle the cream and give it a seltzer-like "sparkling" sensation.
The whipped cream produced with nitrous oxide is unstable, however, and will return to a more liquid state within half an hour to one hour. Thus, the method is not suitable for decorating food that will not be served immediately.
During December 2016, some manufacturers reported a shortage of aerosol whipped creams in the United States due to an explosion at the Air Liquide nitrous oxide facility in Florida in late August. With a major facility offline, the disruption caused a shortage resulting in the company diverting the supply of nitrous oxide to medical clients rather than to food manufacturing. The shortage came during the Christmas and holiday season when canned whipped cream use is normally at its highest.
Similarly, cooking spray, which is made from various types of oils combined with lecithin (an emulsifier), may use nitrous oxide as a propellant. Other propellants used in cooking spray include food-grade alcohol and propane.
Nitrous oxide has been used in dentistry and surgery, as an anaesthetic and analgesic, since 1844. In the early days, the gas was administered through simple inhalers consisting of a breathing bag made of rubber cloth. Today, the gas is administered in hospitals by means of an automated relative analgesia machine, with an anaesthetic vaporiser and a medical ventilator, that delivers a precisely dosed and breath-actuated flow of nitrous oxide mixed with oxygen in a 2:1 ratio.
Nitrous oxide is a weak general anaesthetic, and so is generally not used alone in general anaesthesia, but used as a carrier gas (mixed with oxygen) for more powerful general anaesthetic drugs such as sevoflurane or desflurane. It has a minimum alveolar concentration of 105% and a blood/gas partition coefficient of 0.46. The use of nitrous oxide in anaesthesia, however, can increase the risk of postoperative nausea and vomiting.
Dentists use a simpler machine which only delivers an N2O/O2 mixture for the patient to inhale while conscious. The patient is kept conscious throughout the procedure, and retains adequate mental faculties to respond to questions and instructions from the dentist.
Inhalation of nitrous oxide is used frequently to relieve pain associated with childbirth, trauma, oral surgery and acute coronary syndrome (includes heart attacks). Its use during labour has been shown to be a safe and effective aid for birthing women. Its use for acute coronary syndrome is of unknown benefit.
Fifty percent nitrous oxide can be considered for use by trained non-professional first aid responders in prehospital settings, given the relative ease and safety of administering 50% nitrous oxide as an analgesic. The rapid reversibility of its effect would also prevent it from precluding diagnosis.
Recreational inhalation of nitrous oxide, with the purpose of causing euphoria and/or slight hallucinations, began as a phenomenon for the British upper class in 1799, known as "laughing gas parties".
Starting in the nineteenth century, widespread availability of the gas for medical and culinary purposes allowed the recreational use to expand greatly throughout the world. In the United Kingdom, as of 2014, nitrous oxide was estimated to be used by almost half a million young people at nightspots, festivals and parties. The legality of that use varies greatly from country to country, and even from city to city in some countries.
Widespread recreational use of the drug throughout the UK was featured in the 2017 Vice documentary Inside The Laughing Gas Black Market, in which journalist Matt Shea met with dealers of the drug who stole it from hospitals, although with nitrous oxide canisters being readily available online, the incidents of hospital theft are expected to be extremely rare.
A significant issue cited in London's press is the effect of nitrous oxide canister littering, which is highly visible and causes significant complaint from communities.
The major safety hazards of nitrous oxide come from the fact that it is a compressed liquefied gas, an asphyxiation risk and a dissociative anaesthetic.
While relatively non-toxic, nitrous oxide has a number of recognised ill effects on human health, whether through breathing it in or by contact of the liquid with skin or eyes.
Nitrous oxide is a significant occupational hazard for surgeons, dentists and nurses. Because nitrous oxide is minimally metabolised in humans (with a rate of 0.004%), it retains its potency when exhaled into the room by the patient, and can pose an intoxicating and prolonged exposure hazard to the clinic staff if the room is poorly ventilated. Where nitrous oxide is administered, a continuous-flow fresh-air ventilation system or N2O scavenger system is used to prevent a waste-gas buildup.
The National Institute for Occupational Safety and Health recommends that workers' exposure to nitrous oxide should be controlled during the administration of anaesthetic gas in medical, dental and veterinary operators. It set a recommended exposure limit (REL) of 25 ppm (46 mg/m3) to escaped anaesthetic.
Mental and manual impairment
Exposure to nitrous oxide causes short-term decreases in mental performance, audiovisual ability and manual dexterity. These effects coupled with the induced spatial and temporal disorientation could result in physical harm to the user from environmental hazards.
Neurotoxicity and neuroprotection
Like other NMDA receptor antagonists, it has been suggested that N2O produces neurotoxicity in the form of Olney's lesions in rodents upon prolonged (several hour) exposure. New research has arisen suggesting that Olney's lesions do not occur in humans, however, and similar drugs such as ketamine are now believed not to be acutely neurotoxic. It has been argued that, because N2O is rapidly expelled from the body under normal circumstances, it is less likely to be neurotoxic than other NMDAR antagonists. Indeed, in rodents, short-term exposure results in only mild injury that is rapidly reversible, and neuronal death occurs only after constant and sustained exposure. Nitrous oxide also may cause neurotoxicity after extended exposure because of hypoxia. This is especially true of non-medical formulations such as whipped-cream chargers (also known as "whippets" or "nangs"), which never contain oxygen, since oxygen makes cream rancid.
In heavy (≥400 g or ≥200 L of N
2O gas in one session) or frequent (regular, e.g. daily or weekly) users reported to poison control centers, signs of peripheral neuropathy have been noted: the presence of ataxia (gait abnormalities) or paresthesia (perception of abnormal sensations, e.g. tingling, numbness, prickling, mostly in the extremities). These are considered an early sign of neurological damage and indicates chronic toxicity.
Nitrous oxide at 75% by volume reduces ischemia-induced neuronal death induced by occlusion of the middle cerebral artery in rodents, and decreases NMDA-induced Ca2+ influx in neuronal cell cultures, a critical event involved in excitotoxicity.
Occupational exposure to ambient nitrous oxide has been associated with DNA damage, due to interruptions in DNA synthesis. This correlation is dose-dependent and does not appear to extend to casual recreational use; however, further research is needed to confirm the duration and quantity of exposure needed to cause damage.
If pure nitrous oxide is inhaled without oxygen mixed in, this can eventually lead to oxygen deprivation resulting in loss of blood pressure, fainting and even heart attacks. This can occur if the user inhales large quantities continuously, as with a strap-on mask connected to a gas canister. It can also happen if the user engages in excessive breath-holding or uses any other inhalation system that cuts off a supply of fresh air. A further risk is that symptoms of frostbite can occur on the lips, larynx and bronchi if the gas is inhaled directly from the gas container. Therefore, nitrous oxide is often inhaled from condoms or balloons.
Vitamin B12 deficiency
Long-term exposure to nitrous oxide may cause vitamin B12 deficiency. It inactivates the cobalamin form of vitamin B12 by oxidation. Symptoms of vitamin B12 deficiency, including sensory neuropathy, myelopathy and encephalopathy, may occur within days or weeks of exposure to nitrous oxide anaesthesia in people with subclinical vitamin B12 deficiency.
Symptoms are treated with high doses of vitamin B12, but recovery can be slow and incomplete.
People with normal vitamin B12 levels have stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrous oxide abuse). Vitamin B12 levels should be checked in people with risk factors for vitamin B12 deficiency prior to using nitrous oxide anaesthesia.
At room temperature (20 °C [68 °F]) the saturated vapour pressure is 50.525 bar, rising up to 72.45 bar at 36.4 °C (97.5 °F)—the critical temperature. The pressure curve is thus unusually sensitive to temperature.
As with many strong oxidisers, contamination of parts with fuels have been implicated in rocketry accidents, where small quantities of nitrous/fuel mixtures explode due to "water hammer"-like effects (sometimes called "dieseling"—heating due to adiabatic compression of gases can reach decomposition temperatures). Some common building materials such as stainless steel and aluminium can act as fuels with strong oxidisers such as nitrous oxide, as can contaminants that may ignite due to adiabatic compression.
There also have been incidents where nitrous oxide decomposition in plumbing has led to the explosion of large tanks.
Mechanism of action
The pharmacological mechanism of action of N2O in medicine is not fully known. However, it has been shown to directly modulate a broad range of ligand-gated ion channels, and this likely plays a major role in many of its effects. It moderately blocks NMDAR and β2-subunit-containing nACh channels, weakly inhibits AMPA, kainate, GABAC and 5-HT3 receptors, and slightly potentiates GABAA and glycine receptors. It also has been shown to activate two-pore-domain K+ channels. While N2O affects quite a few ion channels, its anaesthetic, hallucinogenic and euphoriant effects are likely caused predominantly, or fully, via inhibition of NMDA receptor-mediated currents. In addition to its effects on ion channels, N2O may act to imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and anxiolytic properties. Nitrous oxide is 30 to 40 times more soluble than nitrogen.
The effects of inhaling sub-anaesthetic doses of nitrous oxide have been known to vary, based on several factors, including settings and individual differences; however, from his discussion, Jay (2008) suggests that it has been reliably known to induce the following states and sensations:
- Spatial disorientation
- Temporal disorientation
- Reduced pain sensitivity
A minority of users also will present with uncontrolled vocalisations and muscular spasms. These effects generally disappear minutes after removal of the nitrous oxide source.
In rats, N2O stimulates the mesolimbic reward pathway by inducing dopamine release and activating dopaminergic neurons in the ventral tegmental area and nucleus accumbens, presumably through antagonisation of NMDA receptors localised in the system. This action has been implicated in its euphoric effects and, notably, appears to augment its analgesic properties as well.
It is remarkable, however, that in mice, N2O blocks amphetamine-induced carrier-mediated dopamine release in the nucleus accumbens and behavioural sensitisation, abolishes the conditioned place preference (CPP) of cocaine and morphine, and does not produce reinforcing (or aversive) effects of its own. Effects of CPP of N2O in rats are mixed, consisting of reinforcement, aversion and no change. In contrast, it is a positive reinforcer in squirrel monkeys, and is well known as a drug of abuse in humans. These discrepancies in response to N2O may reflect species variation or methodological differences. In human clinical studies, N2O was found to produce mixed responses, similarly to rats, reflecting high subjective individual variability.
In behavioural tests of anxiety, a low dose of N2O is an effective anxiolytic, and this anti-anxiety effect is associated with enhanced activity of GABAA receptors, as it is partially reversed by benzodiazepine receptor antagonists. Mirroring this, animals that have developed tolerance to the anxiolytic effects of benzodiazepines are partially tolerant to N2O. Indeed, in humans given 30% N2O, benzodiazepine receptor antagonists reduced the subjective reports of feeling "high", but did not alter psychomotor performance, in human clinical studies.
The analgesic effects of N2O are linked to the interaction between the endogenous opioid system and the descending noradrenergic system. When animals are given morphine chronically, they develop tolerance to its pain-killing effects, and this also renders the animals tolerant to the analgesic effects of N2O. Administration of antibodies that bind and block the activity of some endogenous opioids (not β-endorphin) also block the antinociceptive effects of N2O. Drugs that inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of N2O. Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of N2O, but these drugs have no effect when injected into the spinal cord.
Conversely, α2-adrenoceptor antagonists block the pain-reducing effects of N2O when given directly to the spinal cord, but not when applied directly to the brain. Indeed, α2B-adrenoceptor knockout mice or animals depleted in norepinephrine are nearly completely resistant to the antinociceptive effects of N2O. Apparently N2O-induced release of endogenous opioids causes disinhibition of brainstem noradrenergic neurons, which release norepinephrine into the spinal cord and inhibit pain signalling. Exactly how N2O causes the release of endogenous opioid peptides remains uncertain.
Properties and reactions
Nitrous oxide is a colourless, non-toxic gas with a faint, sweet odour.
N2O is inert at room temperature and has few reactions. At elevated temperatures, its reactivity increases. For example, nitrous oxide reacts with NaNH2 at 460 K (187 °C) to give NaN3:
- 2 NaNH2 + N2O → NaN3 + NaOH + NH3
The gas was first synthesised in 1772 by English natural philosopher and chemist Joseph Priestley who called it dephlogisticated nitrous air (see phlogiston theory) or inflammable nitrous air. Priestley published his discovery in the book Experiments and Observations on Different Kinds of Air (1775), where he described how to produce the preparation of "nitrous air diminished", by heating iron filings dampened with nitric acid.
The first important use of nitrous oxide was made possible by Thomas Beddoes and James Watt, who worked together to publish the book Considerations on the Medical Use and on the Production of Factitious Airs (1794). This book was important for two reasons. First, James Watt had invented a novel machine to produce "factitious airs" (including nitrous oxide) and a novel "breathing apparatus" to inhale the gas. Second, the book also presented the new medical theories by Thomas Beddoes, that tuberculosis and other lung diseases could be treated by inhalation of "Factitious Airs".
The machine to produce "Factitious Airs" had three parts: a furnace to burn the needed material, a vessel with water where the produced gas passed through in a spiral pipe (for impurities to be "washed off"), and finally the gas cylinder with a gasometer where the gas produced, "air", could be tapped into portable air bags (made of airtight oily silk). The breathing apparatus consisted of one of the portable air bags connected with a tube to a mouthpiece. With this new equipment being engineered and produced by 1794, the way was paved for clinical trials,[clarification needed] which began in 1798 when Thomas Beddoes established the "Pneumatic Institution for Relieving Diseases by Medical Airs" in Hotwells (Bristol). In the basement of the building, a large-scale machine was producing the gases under the supervision of a young Humphry Davy, who was encouraged to experiment with new gases for patients to inhale. The first important work of Davy was examination of the nitrous oxide, and the publication of his results in the book: Researches, Chemical and Philosophical (1800). In that publication, Davy notes the analgesic effect of nitrous oxide at page 465 and its potential to be used for surgical operations at page 556. Davy coined the name "laughing gas" for nitrous oxide.
Despite Davy's discovery that inhalation of nitrous oxide could relieve a conscious person from pain, another 44 years elapsed before doctors attempted to use it for anaesthesia. The use of nitrous oxide as a recreational drug at "laughing gas parties", primarily arranged for the British upper class, became an immediate success beginning in 1799. While the effects of the gas generally make the user appear stuporous, dreamy and sedated, some people also "get the giggles" in a state of euphoria, and frequently erupt in laughter.
The first time nitrous oxide was used as an anaesthetic drug in the treatment of a patient was when dentist Horace Wells, with assistance by Gardner Quincy Colton and John Mankey Riggs, demonstrated insensitivity to pain from a dental extraction on 11 December 1844. In the following weeks, Wells treated the first 12 to 15 patients with nitrous oxide in Hartford, Connecticut, and, according to his own record, only failed in two cases. In spite of these convincing results having been reported by Wells to the medical society in Boston in December 1844, this new method was not immediately adopted by other dentists. The reason for this was most likely that Wells, in January 1845 at his first public demonstration to the medical faculty in Boston, had been partly unsuccessful, leaving his colleagues doubtful regarding its efficacy and safety. The method did not come into general use until 1863, when Gardner Quincy Colton successfully started to use it in all his "Colton Dental Association" clinics, that he had just established in New Haven and New York City . Over the following three years, Colton and his associates successfully administered nitrous oxide to more than 25,000 patients. Today, nitrous oxide is used in dentistry as an anxiolytic, as an adjunct to local anaesthetic.
Nitrous oxide was not found to be a strong enough anaesthetic for use in major surgery in hospital settings, however. Instead, diethyl ether, being a stronger and more potent anaesthetic, was demonstrated and accepted for use in October 1846, along with chloroform in 1847. When Joseph Thomas Clover invented the "gas-ether inhaler" in 1876, however, it became a common practice at hospitals to initiate all anaesthetic treatments with a mild flow of nitrous oxide, and then gradually increase the anaesthesia with the stronger ether or chloroform. Clover's gas-ether inhaler was designed to supply the patient with nitrous oxide and ether at the same time, with the exact mixture being controlled by the operator of the device. It remained in use by many hospitals until the 1930s. Although hospitals today use a more advanced anaesthetic machine, these machines still use the same principle launched with Clover's gas-ether inhaler, to initiate the anaesthesia with nitrous oxide, before the administration of a more powerful anaesthetic.
As a patent medicine
Colton's popularisation of nitrous oxide led to its adoption by a number of less than reputable quacksalvers, who touted it as a cure for consumption, scrofula, catarrh and other diseases of the blood, throat and lungs. Nitrous oxide treatment was administered and licensed as a patent medicine by the likes of C. L. Blood and Jerome Harris in Boston and Charles E. Barney of Chicago.
Reviewing various methods of producing nitrous oxide is published.
- NH4NO3 → 2 H2O + N2O
- 2 NaNO3 + (NH4)2SO4 → Na2SO4 + 2 N2O + 4 H2O
Another method involves the reaction of urea, nitric acid and sulfuric acid:
- 2 (NH2)2CO + 2 HNO3 + H2SO4 → 2 N2O + 2 CO2 + (NH4)2SO4 + 2 H2O
- 2 NH3 + 2 O2 → N2O + 3 H2O
Hydroxylammonium chloride reacts with sodium nitrite to give nitrous oxide. If the nitrite is added to the hydroxylamine solution, the only remaining by-product is salt water. If the hydroxylamine solution is added to the nitrite solution (nitrite is in excess), however, then toxic higher oxides of nitrogen also are formed:
- NH3OHCl + NaNO2 → N2O + NaCl + 2 H2O
Treating HNO3 with SnCl2 and HCl also has been demonstrated:
- 2 HNO3 + 8 HCl + 4 SnCl2 → 5 H2O + 4 SnCl4 + N2O
- H2N2O2→ H2O + N2O
Nitrous oxide is a minor component of Earth's atmosphere and is an active part of the planetary nitrogen cycle. Based on analysis of air samples gathered from sites around the world, its concentration surpassed 330 ppb in 2017. The growth rate of about 1 ppb per year has also accelerated during recent decades. Nitrous oxide's atmospheric abundance has grown more than 20% from a base level of about 270 ppb in year 1750. Important atmospheric properties of N2O are summarized in the following table:
|Ozone depletion potential (ODP)||0.17 (CCl3F = 1)|
|Global warming potential (GWP: 100-year)||265 (CO2 = 1)|
|Atmospheric lifetime||121 years|
In October 2020 scientists published a comprehensive quantification of global N2O sources and sinks. They report that human-induced emissions increased by 30% over the past four decades and are the main cause of the increase in atmospheric concentration. The recent growth has exceeded some of the highest projected emission scenarios.
Emissions by source
As of 2010, it was estimated that about 29.5 million tonnes of N2O (containing 18.8 million tonnes of nitrogen) were entering the atmosphere each year; of which 64% were natural, and 36% due to human activity.
Most of the N2O emitted into the atmosphere, from natural and anthropogenic sources, is produced by microorganisms such as denitrifying bacteria and fungi in soils and oceans. Soils under natural vegetation are an important source of nitrous oxide, accounting for 60% of all naturally produced emissions. Other natural sources include the oceans (35%) and atmospheric chemical reactions (5%).
A 2019 study showed that emissions from thawing permafrost are 12 times higher than previously assumed.
The main components of anthropogenic emissions are fertilised agricultural soils and livestock manure (42%), runoff and leaching of fertilisers (25%), biomass burning (10%), fossil fuel combustion and industrial processes (10%), biological degradation of other nitrogen-containing atmospheric emissions (9%) and human sewage (5%). Agriculture enhances nitrous oxide production through soil cultivation, the use of nitrogen fertilisers and animal waste handling. These activities stimulate naturally occurring bacteria to produce more nitrous oxide. Nitrous oxide emissions from soil can be challenging to measure as they vary markedly over time and space, and the majority of a year's emissions may occur when conditions are favorable during "hot moments" and/or at favorable locations known as "hotspots".
Among industrial emissions, the production of nitric acid and adipic acid are the largest sources of nitrous oxide emissions. The adipic acid emissions specifically arise from the degradation of the nitrolic acid intermediate derived from nitration of cyclohexanone.
- aerobic autotrophic nitrification, the stepwise oxidation of ammonia (NH3) to nitrite (NO−2) and to nitrate (NO−3)
- anaerobic heterotrophic denitrification, the stepwise reduction of NO−3 to NO−2, nitric oxide (NO), N2O and ultimately N2, where facultative anaerobe bacteria use NO−3 as an electron acceptor in the respiration of organic material in the condition of insufficient oxygen (O2)
- nitrifier denitrification, which is carried out by autotrophic NH3-oxidising bacteria and the pathway whereby ammonia (NH3) is oxidised to nitrite (NO−2), followed by the reduction of NO−2 to nitric oxide (NO), N2O and molecular nitrogen (N2)
- heterotrophic nitrification
- aerobic denitrification by the same heterotrophic nitrifiers
- fungal denitrification
- non-biological chemodenitrification
These processes are affected by soil chemical and physical properties such as the availability of mineral nitrogen and organic matter, acidity and soil type, as well as climate-related factors such as soil temperature and water content.
Nitrous oxide has significant global warming potential as a greenhouse gas. On a per-molecule basis, considered over a 100-year period, nitrous oxide has 265 times the atmospheric heat-trapping ability of carbon dioxide (CO2). However, because of its low concentration (less than 1/1,000 of that of CO2), its contribution to the greenhouse effect is less than one third that of carbon dioxide, and also less than water vapour and methane. On the other hand, since 38% or more of the N2O entering the atmosphere is the result of human activity, control of nitrous oxide is considered part of efforts to curb greenhouse gas emissions.
A 2008 study by Nobel Laureate Paul Crutzen suggests that the amount of nitrous oxide release attributable to agricultural nitrate fertilisers has been seriously underestimated, most of which presumably, would come under soil and oceanic release in the Environmental Protection Agency data.
Nitrous oxide is released into the atmosphere through agriculture, when farmers add nitrogen-based fertilizers onto the fields, through the breakdown of animal manure. Approximately 79 percent of all nitrous oxide released in the United States came from nitrogen fertilization. Nitrous oxide is also released as a by-product of burning fossil fuel, though the amount released depends on which fuel was used. It is also emitted through the manufacture of nitric acid, which is used in the synthesis of nitrogen fertilizers. The production of adipic acid, a precursor to nylon and other synthetic clothing fibres, also releases nitrous oxide. The total amount of nitrous oxide released that is of human origins is about 40 percent.
Ozone layer depletion
Nitrous oxide has also been implicated in thinning the ozone layer. A 2009 study suggested that N2O emission was the single most important ozone-depleting emission and it was expected to remain the largest throughout the 21st century.
In the United States , possession of nitrous oxide is legal under federal law and is not subject to DEA purview. It is, however, regulated by the Food and Drug Administration under the Food Drug and Cosmetics Act; prosecution is possible under its "misbranding" clauses, prohibiting the sale or distribution of nitrous oxide for the purpose of human consumption. Many states have laws regulating the possession, sale and distribution of nitrous oxide. Such laws usually ban distribution to minors or limit the amount of nitrous oxide that may be sold without special license. For example, in the state of California, possession for recreational use is prohibited and qualifies as a misdemeanor.
In August 2015, the Council of the London Borough of Lambeth (United Kingdom ) banned the use of the drug for recreational purposes, making offenders liable to an on-the-spot fine of up to £1,000.
In New Zealand, the Ministry of Health has warned that nitrous oxide is a prescription medicine, and its sale or possession without a prescription is an offense under the Medicines Act. This statement would seemingly prohibit all non-medicinal uses of nitrous oxide, although it is implied that only recreational use will be targeted legally.
- "Nitrous oxide". https://pubchem.ncbi.nlm.nih.gov/compound/948#section=IUPAC-Name&fullscreen=true.
- Takahashi, Mitsuo; Shibasaki-Kitakawa, Naomi; Yokoyama, Chiaki; Takahashi, Shinji (1996). "Viscosity of Gaseous Nitrous Oxide from 298.15 K to 398.15 K at Pressures up to 25 MPa". Journal of Chemical & Engineering Data 41 (6): 1495–1498. doi:10.1021/je960060d. ISSN 0021-9568.
- Tarendash, Albert S. (2001). Let's review: chemistry, the physical setting (3rd ed.). Barron's Educational Series. p. 44. ISBN 978-0-7641-1664-3. https://archive.org/details/letsreviewchemis03edtare.
- PubChem. "Nitrous oxide" (in en). https://pubchem.ncbi.nlm.nih.gov/compound/948.
- "Frostbite injury: An unknown risk when using nitrous oxide as a party drug". Acta Chirurgica Belgica (Taylor & Francis on behalf of the Royal Belgian Society for Surgery) 120 (1–4): 140–143. July 2020. doi:10.1080/00015458.2020.1782160. ISSN 0001-5458. PMID 32543291.
- World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- "Nitrous Oxide (N2O) Mole Fraction". Massachusettes Institute of Technology. https://agage2.eas.gatech.edu/data_archive/data_figures/monthly/pdf/N2O_mm.pdf.
- "Trends in Atmospheric Nitrous Oxide". National Oceanic and Atmospheric Administration / Earth System Research Laboratories. https://www.esrl.noaa.gov/gmd/ccgg/trends_n2o/.
- Ravishankara, A. R.; Daniel, J. S.; Portmann, R. W. (2009). "Nitrous Oxide (N2O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century". Science 326 (5949): 123–5. doi:10.1126/science.1176985. PMID 19713491. Bibcode: 2009Sci...326..123R. https://semanticscholar.org/paper/4d99f9f4f310c42516037712b5610ffb820ad32b.
- Tian, HanqinExpression error: Unrecognized word "et". (October 2020). "A comprehensive quantification of global nitrous oxide sources and sinks" (in en). Nature 586 (7828): 248–256. doi:10.1038/s41586-020-2780-0. ISSN 1476-4687. PMID 33028999. Bibcode: 2020Natur.586..248T. https://www.nature.com/articles/s41586-020-2780-0. Retrieved 2020-11-09.
- Thompson, R. L., Lassaletta, L., Patra, P. K. (2019). "Acceleration of global N2O emissions seen from two decades of atmospheric inversion". Nat. Clim. Change 9 (12): 993–998. doi:10.1038/s41558-019-0613-7. Bibcode: 2019NatCC...9..993T. http://pure.iiasa.ac.at/id/eprint/16173/2/N2O_paper_SI_revision2_v1.docx.
- "Chapter 8". AR5 Climate Change 2013: The Physical Science Basis. pp. 677–678. https://www.ipcc.ch/report/ar5/wg1/.
- "Nitrous oxide emissions pose an increasing climate threat, study finds" (in en). phys.org. https://phys.org/news/2020-10-nitrous-oxide-emissions-pose-climate.html.
- Berger, Bruno (5 October 2007). "Is nitrous oxide safe?". Swiss Propulsion Laboratory. pp. 1–2. http://www.spl.ch/publication/SPL_Papers/N2O_safety_e.pdf. "...Self pressurizing (Vapor pressure at 20°C is ~50.1 bar...Nontoxic, low reactivity -> rel. safe handling (General safe ???)...Additional energy from decomposition (as a monopropellant: ISP of 170 s)...Specific impulse doesn't change much with O/F...[page 2] N2O is a monopropellant (as H2O2 or Hydrazine...)"
- Goddard, R. H. (1914) "Rocket apparatus" U.S. Patent 1,103,503
- Nitrous Oxide Safety. Space Propulsion Group (2012)
- Munke, Konrad (2 July 2001) Nitrous Oxide Trailer Rupture, Report at CGA Seminar "Safety and Reliability of Industrial Gases, Equipment and Facilities", 15–17 October 2001, St. Louis, Missouri
- "Scaled Composites Safety Guidelines for N2O". Scaled Composites. 17 June 2009. http://www.scaled.com/images/uploads/news/N2OSafetyGuidelines.pdf. "For example, N2O flowing at 130 psi in an epoxy composite pipe would not react even with a 2500 J ignition energy input. At 600 psi, however, the required ignition energy was only 6 J."
- FR-5904. Pratt & Whitney Aircraft.
- Cline, Allen W. (January 2000) "Engine Basics: Detonation and Pre-Ignition". CONTACT! Magazine
- "Holley performance products, FAQ for Nitrous Oxide Systems". Holley. https://www.holley.com/support/faq/?category=NOS.
- "Explora Science | Nitrous use as a propellant and in cooking" (in en-US). http://www.explora-science.net/nitrousoxide-use-as-a-propellant-and-in-cooking/.
- Dewey, Caitlin (2016-12-21). "The real reason grocery stores are running out of whipped cream this Christmas". The Washington Post. https://www.washingtonpost.com/news/wonk/wp/2016/12/21/the-real-reason-you-cant-buy-whipped-cream-this-christmas/.
- Sneader W (2005). Drug Discovery –A History. John Wiley and Sons. ISBN 978-0-471-89980-8. https://books.google.com/books?id=mYQxRY9umjcC. Retrieved 21 April 2010.
- Miller AH (1941). "Technical Development of Gas Anesthesia". Anesthesiology 2 (4): 398–409. doi:10.1097/00000542-194107000-00004.
- Divatia, Jigeeshu V.; Vaidya, Jayant S.; Badwe, Rajendra A.; Hawaldar, Rohini W. (1996). "Omission of Nitrous Oxide during Anesthesia Reduces the Incidence of Postoperative Nausea and Vomiting". Anesthesiology 85 (5): 1055–1062. doi:10.1097/00000542-199611000-00014. PMID 8916823. https://semanticscholar.org/paper/a845666e10d59515e6f6b3c524486cd501af9b80.
- Hartung, John (1996). "Twenty-Four of Twenty-Seven Studies Show a Greater Incidence of Emesis Associated with Nitrous Oxide than with Alternative Anesthetics". Anesthesia & Analgesia 83 (1): 114–116. doi:10.1213/00000539-199607000-00020.
- Tramèr, M.; Moore, A.; McQuay, H. (February 1996). "Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials". British Journal of Anaesthesia 76 (2): 186–193. doi:10.1093/bja/76.2.186. PMID 8777095.
- Council on Clinical Affairs (2013). "Guideline on use of nitrous oxide for pediatric dental patients". Reference Manual V37 6: 206–210. http://www.aapd.org/media/policies_guidelines/g_nitrous.pdf.
- Copeland, Claudia. "Nitrous Oxide Analgesia for Childbirth". http://www.pregnancy.org/article/nitrous-oxide-analgesia-child-birth.
- O'Connor RE; Brady W; Brooks SC; Diercks, D.; Egan, J.; Ghaemmaghami, C.; Menon, V.; O'Neil, B. J. et al. (2010). "Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation 122 (18 Suppl 3): S787–817. doi:10.1161/CIRCULATIONAHA.110.971028. PMID 20956226.
- Faddy, S. C.; Garlick, S. R. (2005-12-01). "A systematic review of the safety of analgesia with 50% nitrous oxide: can lay responders use analgesic gases in the prehospital setting?". Emergency Medicine Journal 22 (12): 901–908. doi:10.1136/emj.2004.020891. PMID 16299211.
- Davy, Humphry (1800). Researches, chemical and philosophical : chiefly concerning nitrous oxide, or diphlogisticated nitrous air, and its respiration. Francis A. Countway Library of Medicine. London : printed for J. Johnson, St. Paul's Church-Yard, by Biggs and Cottle, Bristol. http://archive.org/details/researcheschemic00davy.
- "Warning over laughing gas misuse". The Guardian. Press Association (London). 9 August 2014. https://www.theguardian.com/politics/2014/aug/09/warning-over-laughing-gas-misuse.
- VICE (2017-02-07), Inside The Laughing Gas Black Market, https://www.youtube.com/watch?v=gdhdAktIHtg, retrieved 2019-03-29
- "Recycling used laughing gas canisters for cash could help create a cleaner Britain" (in en-US). 2018-07-10. https://metro.co.uk/2018/07/10/recycling-used-laughing-gas-canisters-for-cash-could-help-create-a-cleaner-britain-7694925/.
- CDC.gov NIOSH Alert: Controlling Exposures to Nitrous Oxide During Anesthetic Administration. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 94-100
- "CDC – NIOSH Pocket Guide to Chemical Hazards – Nitrous oxide". https://www.cdc.gov/niosh/npg/npgd0465.html.
- Criteria for a recommended standard: occupational exposure to waste anesthetic gases and vapors. Cincinnati, OH: U.S. Department of Health, Education, and Welfare, Public Health Service, Center for Disease Control, National Institute for Occupational Safety and Health, DHEW (NIOSH) Publication No. 77B140.
- "Nitrous oxide: recreational use, regulation and harm reduction". Drugs and Alcohol Today 8 (3): 22–25. 2008-09-01. doi:10.1108/17459265200800022.
- "Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain". Neuroscience 122 (3): 609–16. 2003. doi:10.1016/j.neuroscience.2003.07.012. PMID 14622904. https://www.semanticscholar.org/paper/278210b62f0dd2ee8cafd9136bac010d8ade00e1.
- "NMDA receptor antagonist neurotoxicity and psychotomimetic activity" (in ja). Masui. The Japanese Journal of Anesthesiology 52 (6): 594–602. 2003. PMID 12854473.
- "Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats". British Journal of Pharmacology 130 (7): 1692–8. 2000. doi:10.1038/sj.bjp.0703479. PMID 10928976.
- Jevtovic-Todorovic V, Carter LB; Carter (2005). "The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to young rat brain". Neurobiology of Aging 26 (6): 947–56. doi:10.1016/j.neurobiolaging.2004.07.009. PMID 15718054. https://www.semanticscholar.org/paper/c282c0078f2129a86d3875a758c8c23b46332df0.
- Slikker, W.; Zou, X.; Hotchkiss, C. E.; Divine, R. L.; Sadovova, N.; Twaddle, N. C.; Doerge, D. R.; Scallet, A. C. et al. (2007). "Ketamine-Induced Neuronal Cell Death in the Perinatal Rhesus Monkey". Toxicological Sciences 98 (1): 145–158. doi:10.1093/toxsci/kfm084. PMID 17426105.
- Sun, Lin; Qi Li; Qing Li; Yuzhe Zhang; Dexiang Liu; Hong Jiang; Fang Pan; David T. Yew (November 2012). "Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys". Addiction Biology 19 (2): 185–94. doi:10.1111/adb.12004. PMID 23145560.
- "Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon". Annals of the New York Academy of Sciences 1053 (1): 289–300. 2005. doi:10.1111/j.1749-6632.2005.tb00036.x. PMID 16179534. Bibcode: 2005NYASA1053..289A.
- De Vasconcellos, K.; Sneyd, J. R. (2013). "Nitrous oxide: Are we still in equipoise? A qualitative review of current controversies". British Journal of Anaesthesia 111 (6): 877–85. doi:10.1093/bja/aet215. PMID 23801743.
- Middleton, Ben (2012). Physics in anaesthesia. Banbury, Oxfordshire, UK: Scion Pub. Ltd. ISBN 978-1-904842-98-9.
- van Riel, A.J.H.P. (2022). "Alarming increase in poisonings from recreational nitrous oxide use after a change in EU-legislation, inquiries to the Dutch Poisons Information Center". International Journal of Drug Policy 100: 103519. doi:10.1016/j.drugpo.2021.103519. PMID 34753046.
- Flippo, T. S.; Holder Jr, W. D. (1993). "Neurologic Degeneration Associated with Nitrous Oxide Anesthesia in Patients with Vitamin B12 Deficiency". Archives of Surgery 128 (12): 1391–5. doi:10.1001/archsurg.1993.01420240099018. PMID 8250714.
- Randhawa, G.; Bodenham, A. (1 March 2016). "The increasing recreational use of nitrous oxide: history revisited" (in en). pp. 321–324. doi:10.1093/bja/aev297. https://academic.oup.com/bja/article/116/3/321/2566058.
- Wrońska-Nofer, Teresa; Nofer, Jerzy-Roch; Jajte, Jolanta; Dziubałtowska, Elżbieta; Szymczak, Wiesław; Krajewski, Wojciech; Wąsowicz, Wojciech; Rydzyński, Konrad (1 March 2012). "Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N2O)". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 731 (1): 58–63. doi:10.1016/j.mrfmmm.2011.10.010. PMID 22085808.
- Wrońska-Nofer, Teresa; Palus, Jadwiga; Krajewski, Wojciech; Jajte, Jolanta; Kucharska, Małgorzata; Stetkiewicz, Jan; Wąsowicz, Wojciech; Rydzyński, Konrad (18 June 2009). "DNA damage induced by nitrous oxide: Study in medical personnel of operating rooms". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 666 (1–2): 39–43. doi:10.1016/j.mrfmmm.2009.03.012. PMID 19439331.
- Dangers of Nitrous Oxide. Just Say N2O
- van Amsterdam, Jan; Nabben, Ton; van den Brink, Wim (2015-10-22). "Recreational nitrous oxide use: Prevalence and risks". Regulatory Toxicology and Pharmacology 73 (3): 790–796. doi:10.1016/j.yrtph.2015.10.017. ISSN 1096-0295. PMID 26496821. https://pubmed.ncbi.nlm.nih.gov/26496821/.
- Giannini, A.J. (1999). Drug Abuse. Los Angeles: Health Information Press. ISBN 978-1-885987-11-2. https://archive.org/details/drugabuse00ajam.
- Conrad, Marcel (4 October 2006). Pernicious Anemia. http://www.emedicine.com/med/topic1799.htm. Retrieved 2 June 2008.
- Vieira, E.; Cleaton-Jones, P.; Austin, J.C.; Moyes, D.G.; Shaw, R. (1980). "Effects of low concentrations of nitrous oxide on rat fetuses". Anesthesia and Analgesia 59 (3): 175–7. doi:10.1213/00000539-198003000-00002. PMID 7189346.
- Vieira, E. (1979). "Effect of the chronic administration of nitrous oxide 0.5% to gravid rats". British Journal of Anaesthesia 51 (4): 283–7. doi:10.1093/bja/51.4.283. PMID 465253.
- Vieira, E; Cleaton-Jones, P; Moyes, D. (1983). "Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus". British Journal of Anaesthesia 55 (1): 67–9. doi:10.1093/bja/55.1.67. PMID 6821624.
- Nitrous oxide. Air Liquide Gas Encyclopedia.
- "Vaseline triggered explosion of hybrid rocket". Ukrocketman.com. http://www.ukrocketman.com/rocketry/hybridukhistory.shtml.
- "Safetygram 20: Nitrous Oxide". Airproducts.com. http://www.airproducts.com/nr/rdonlyres/8c46596e-2f7d-4895-b12a-e54cd63e1996/0/safetygram20.pdf.
- "Effects of gaseous anaesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol". Anesthesiology 93 (4): 1095–101. 2000. doi:10.1097/00000542-200010000-00034. PMID 11020766.
- "Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures". Journal of Neuroscience 18 (23): 9716–26. 1998. doi:10.1523/JNEUROSCI.18-23-09716.1998. PMID 9822732.
- "Two-pore-domain K+ channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane". Molecular Pharmacology 65 (2): 443–52. 2004. doi:10.1124/mol.65.2.443. PMID 14742687. https://semanticscholar.org/paper/bea469f6209d4dbf29e33ae167a6c7ef8f54a298.
- "Advances in Understanding the Actions of Nitrous Oxide". Anesthesia Progress 54 (1): 9–18. 2007. doi:10.2344/0003-3006(2007)54[9:AIUTAO2.0.CO;2]. PMID 17352529.
- Atkinson, Roland M.; Green, J. DeWayne; Chenoweth, Dennis E.; Atkinson, Judith Holmes (1979-10-01). "Subjective Effects of Nitrous Oxide: Cognitive, Emotional, Perceptual and Transcendental Experiences". Journal of Psychedelic Drugs 11 (4): 317–330. doi:10.1080/02791072.1979.10471415. PMID 522172.
- Walker, Diana J.; Zacny, James P. (2001-09-01). "Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers". Drug and Alcohol Dependence 64 (1): 85–96. doi:10.1016/s0376-8716(00)00234-9. PMID 11470344.
- "The differential effects of nitrous oxide and xenon on extracellular dopamine levels in the rat nucleus accumbens: a microdialysis study". Anesthesia and Analgesia 103 (6): 1459–63. 2006. doi:10.1213/01.ane.0000247792.03959.f1. PMID 17122223.
- "Effects of nitrous oxide on dopamine release in the rat nucleus accumbens and expectation of reward". Neuroscience 155 (2): 341–4. 2008. doi:10.1016/j.neuroscience.2008.05.015. PMID 18571333. https://www.hal.inserm.fr/inserm-00292354/file/Figure_1.pdf.
- "Role of dopamine mesolimbic system in opioid action of psychotropic analgesic nitrous oxide in alcohol and drug withdrawal". Clinical Neuropharmacology 19 (3): 246–51. 1996. doi:10.1097/00002826-199619030-00006. PMID 8726543.
- "Dopamine D2-like receptor in the nucleus accumbens is involved in the antinociceptive effect of nitrous oxide". Anesthesia and Analgesia 106 (6): 1904–9. 2008. doi:10.1213/ane.0b013e318172b15b. PMID 18499630.
- "Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization". Biological Psychiatry 60 (1): 49–57. 2006. doi:10.1016/j.biopsych.2005.10.007. PMID 16427030. https://www.semanticscholar.org/paper/d10874c17d0ddc206cfdf830c7370ddd08420f5f.
- "Specific blockade of morphine- and cocaine-induced reinforcing effects in conditioned place preference by nitrous oxide in mice". Neuroscience 149 (3): 477–86. 2007. doi:10.1016/j.neuroscience.2007.08.003. PMID 17905521. http://www.hal.inserm.fr/inserm-00292333/document.
- "Conditioned place aversion and self-administration of nitrous oxide in rats". Pharmacology Biochemistry and Behavior 74 (3): 623–33. 2003. doi:10.1016/S0091-3057(02)01048-1. PMID 12543228. https://www.semanticscholar.org/paper/4872b2f16a2a9ec69f52d0f5aabab812af3a768a.
- "Nitrous oxide self-administration by the squirrel monkey". The Journal of Pharmacology and Experimental Therapeutics 202 (3): 491–9. 1977. PMID 408480.
- "Psychotropic drugs used in anesthesia practice: abuse liability and epidemiology of abuse". Anesthesiology 90 (1): 269–88. 1999. doi:10.1097/00000542-199901000-00033. PMID 9915336.
- "Reinforcing effects of extended inhalation of nitrous oxide in humans". Drug and Alcohol Dependence 31 (3): 265–80. 1993. doi:10.1016/0376-8716(93)90009-F. PMID 8462415.
- "Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers". Drug and Alcohol Dependence 64 (1): 85–96. 2001. doi:10.1016/S0376-8716(00)00234-9. PMID 11470344.
- "Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors". Psychopharmacology 115 (1–2): 167–72. 1994. doi:10.1007/BF02244768. PMID 7862891. https://www.semanticscholar.org/paper/6f042c60b815a9a61d808f0913bdaa73fffcc253.
- "Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report". Pharmacology Biochemistry and Behavior 51 (4): 815–9. 1995. doi:10.1016/0091-3057(95)00039-Y. PMID 7675863. https://www.semanticscholar.org/paper/8aa3c67fe1064a205542499b778a8a903c9151c3.
- "Tolerance to nitrous oxide analgesia in rats and mice". Anesthesiology 51 (4): 309–12. 1979. doi:10.1097/00000542-197910000-00006. PMID 484891.
- "Role of brain dynorphin in nitrous oxide antinociception in mice". Pharmacology Biochemistry and Behavior 65 (2): 217–21. 2000. doi:10.1016/S0091-3057(99)00202-6. PMID 10672972. https://www.semanticscholar.org/paper/bab67d14373e7e5f03c6485e6ce47e93459eaf2a.
- Gillman M.A. [1986a]. Minireview: Analgesic [sub anaesthetic] nitrous oxide interacts with the endogenous opioid system : A review of the evidence. Life Sciences 39: l209-l22l
- (Daras, C., Cantrill, R. C., Gillman, M. A. . 3[H]-Naloxone displacement: evidence for nitrous oxide as an opioid agonist. European Journal of Pharmacology 89: 177-8.
- Ori, C., Ford-Rice, F., London, E. D. . Effects of nitrous oxide and halothane on mu and kappa opioid receptors in guinea-pig brain. Anesthesiology 70: 541-544.)
- "Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice". Anesthesiology 90 (2): 470–6. 1999. doi:10.1097/00000542-199902000-00022. PMID 9952154.
- "Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha2B adrenoceptors"]. J. Neurosci. 20 (24): 9242–51. 2000. doi:10.1523/JNEUROSCI.20-24-09242.2000. PMID 11125002.
- "Recent advances in understanding the actions and toxicity of nitrous oxide". Anaesthesia 55 (4): 311–4. 2000. doi:10.1046/j.1365-2044.2000.01463.x. PMID 10781114.
- Housecroft, Catherine E.; Sharpe, Alan G. (2008). "Chapter 15: The group 15 elements". Inorganic Chemistry (3rd ed.). Pearson. p. 464. ISBN 978-0-13-175553-6. https://archive.org/details/inorganicchemist00hous_159.
- Keys, T.E. (1941). "The Development of Anesthesia". Anesthesiology 2 (5): 552–574. doi:10.1097/00000542-194109000-00008. Bibcode: 1982AmSci..70..522D.
- McEvoy, J. G. (6 March 2015). "Gases, God and the balance of nature: a commentary on Priestley (1772) 'Observations on different kinds of air'". Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 373 (2039): 20140229. doi:10.1098/rsta.2014.0229. PMID 25750146. Bibcode: 2015RSPTA.37340229M.
- Priestley J (1776). Experiments and Observations on Different Kinds of Air. 2. http://www.erowid.org/chemicals/nitrous/nitrous_journal1.shtml.
- Davy H (1800). Researches, chemical and philosophical –chiefly concerning nitrous oxide or dephlogisticated nitrous air, and its respiration. Printed for J. Johnson. https://books.google.com/books?id=jhUAAAAAQAAJ.
- Hardman, Jonathan G. (2017). Oxford Textbook of Anaesthesia. Oxford University Press. p. 529. ISBN 9780199642045.
- Brecher EM (1972). "Consumers Union Report on Licit and Illicit Drugs, Part VI – Inhalants and Solvents and Glue-Sniffing". Consumer Reports Magazine. http://www.druglibrary.org/schaffer/Library/studies/cu/CU43.html.
- "George Poe is Dead". Washington Post. 3 February 1914. https://pqasb.pqarchiver.com/washingtonpost_historical/access/243050292.html?dids=243050292:243050292&FMT=ABS&FMTS=ABS:FT&date=FEB+03%2C+1914&author=&pub=The+Washington+Post&desc=GEORGE+POE+IS+DEAD&pqatl=google.
- Erving, H. W. (1933). "The Discoverer of Anæsthesia: Dr. Horace Wells of Hartford.". The Yale Journal of Biology and Medicine 5 (5): 421–430. PMID 21433572.
- Wells H (1847). A history of the discovery, of the application of nitrous oxide gas, ether, and other vapours, to surgical operations. J. Gaylord Wells. https://books.google.com/books?id=exNtlBi8T4EC.
- "The discovery of modern anaesthesia-contributions of Davy, Clarke, Long, Wells and Morton". Indian J Anaesth 51 (6): 472–8. 2007. http://www.ijaweb.org/text.asp?2007/51/6/472/61183.
- "Alleged Forgery". The Inter Ocean: p. 8. 1877-09-28. https://www.newspapers.com/clip/3461701/alleged_forgery/.
- "A Man of Ominous Name". The Inter Ocean. 1890-02-19. https://www.newspapers.com/clip/3461943/dr_blood_and_the_sawtelles/.
- Parmon, V. N.; Panov, G. I.; Uriarte, A.; Noskov, A. S. (2005). "Nitrous oxide in oxidation chemistry and catalysis application and production". Catalysis Today 100 (2005): 115–131. doi:10.1016/j.cattod.2004.12.012.
- Holleman, A. F.; Wiberg, E. (2001). Inorganic Chemistry. San Diego: Academic Press. ISBN 978-0-12-352651-9.
- "Nitrous oxide plant". Sanghi Organization. http://www.sanghioverseas.com/nitrous_oxide_gas_plants/nitrous_oxide_gas_plants.htm.
- "Nitrogen Family". chemistry.tutorvista.com
- "Preparation of Nitrous Oxide from Urea, Nitric Acid and Sulfuric Acid".
- "Manufacture of Nitrous Oxide by the Catalytic Oxidation of Ammonia". The Journal of the Society of Chemical Industry, Japan 64 (11): 1879–1888. 1961. doi:10.1246/nikkashi1898.64.11_1879.
- Egon Wiberg, Arnold Frederick Holleman (2001) Inorganic Chemistry, Elsevier ISBN:0-12-352651-5
- "N2O Budget". Global Carbon Project. https://www.globalcarbonproject.org/nitrousoxidebudget/index.htm.
- "Chapter 6". TAR Climate Change 2001: The Scientific Basis. p. 358. https://www.ipcc.ch/report/ar3/wg1/.
- Ravishankara, A. R.; Daniel, John S.; Portmann, Robert W. (2009-08-27), "Supporting Online Material for - Nitrous Oxide (N2O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century", Science 326 (5949): 123–125, doi:10.1126/science.1176985, PMID 19713491, Bibcode: 2009Sci...326..123R, https://www.sciencemag.org/content/suppl/2009/08/27/1176985.DC1/Ravishankara.SOM.pdf
- "Chapter 8". AR5 Climate Change 2013: The Physical Science Basis. p. 731. https://www.ipcc.ch/report/ar5/wg1/.
- U.S. Environmental Protection Agency (2010), "Methane and Nitrous Oxide Emissions from Natural Sources". Report EPA 430-R-10-001.
- "2011 U.S. Greenhouse Gas Inventory Report". U.S. Environmental Protection Agency. February 2011. http://www.epa.gov/climatechange/emissions/usinventoryreport.html.
- Sloss, Leslie L. (1992). Nitrogen Oxides Control Technology Fact Book. William Andrew. p. 6. ISBN 978-0-8155-1294-3. https://books.google.com/books?id=--C_JAU7W8QC&pg=PA6.
- McDermott-Murphy, Caitlin (6 June 2019). "No laughing matter". The Harvard Gazette. https://news.harvard.edu/gazette/story/2019/06/harvard-chemist-permafrost-n2o-levels-12-times-higher-than-expected/. Retrieved 22 July 2019.
- K. L. Denman, G. Brasseur, et al. (2007), "Couplings Between Changes in the Climate System and Biogeochemistry". In Fourth Assessment Report of the Intergovernmental Panel on Climate Change, Cambridge University Press.
- Steinfeld, H.; Gerber, P.; Wassenaar, T.; Castel, V.; Rosales, M.; de Haan, C. (2006). Livestock's long shadow: Environmental issues and options. Fao.org. http://www.fao.org/docrep/010/a0701e/a0701e00.HTM. Retrieved 2 February 2008.
- "Overview of Greenhouse Gases: Nitrous Oxide". U.S. Environmental Protection Agency. 23 December 2015. https://www3.epa.gov/climatechange/ghgemissions/gases/n2o.html.
- "Nitrous Oxide: Sources and Emissions". U.S. Environmental Protection Agency. 2006. http://www.epa.gov/nitrousoxide/sources.html.
- IPCC. 2013. Climate change: the physical basis (WG I, full report). p. 512.
- Thompson, R. L.; Lassaletta, L.; Patra, P. K.; Wilson, C.; Wells, K. C.; Gressent, A.; Koffi, E. N.; Chipperfield, M. P. et al. (2019-11-18). "Acceleration of global N 2 O emissions seen from two decades of atmospheric inversion" (in en). Nature Climate Change 9 (12): 993–998. doi:10.1038/s41558-019-0613-7. ISSN 1758-6798. Bibcode: 2019NatCC...9..993T. http://pure.iiasa.ac.at/id/eprint/16173/2/N2O_paper_SI_revision2_v1.docx.
- Molodovskaya, Marina; Warland, Jon; Richards, Brian K.; Öberg, Gunilla; Steenhuis, Tammo S. (2011). "Nitrous Oxide from Heterogeneous Agricultural Landscapes: Source Contribution Analysis by Eddy Covariance and Chambers". Soil Science Society of America Journal 75 (5): 1829. doi:10.2136/SSSAJ2010.0415. Bibcode: 2011SSASJ..75.1829M.
- Molodovskaya, M.; Singurindy, O.; Richards, B. K.; Warland, J. S.; Johnson, M.; Öberg, G.; Steenhuis, T. S. (2012). "Temporal variability of nitrous oxide from fertilized croplands: hot moment analysis". Soil Science Society of America Journal 76 (5): 1728–1740. doi:10.2136/sssaj2012.0039. Bibcode: 2012SSASJ..76.1728M. https://semanticscholar.org/paper/ba51c23c37aa3a7fb895853d77ff4ad8ceef7471.
- Singurindy, Olga; Molodovskaya, Marina; Richards, Brian K.; Steenhuis, Tammo S. (July 2009). "Nitrous oxide emission at low temperatures from manure-amended soils under corn (Zea mays L.)". Agriculture, Ecosystems & Environment 132 (1–2): 74–81. doi:10.1016/j.agee.2009.03.001.
- Mason, C.W.; Stoof, C.R.; Richards, B.K.; Das, S.; Goodale, C.L.; Steenhuis, T.S. (2017). "Hotspots of nitrous oxide emission in fertilized and unfertilized perennial grasses on wetness-prone marginal land in New York State". Soil Science Society of America Journal 81 (3): 450–458. doi:10.2136/sssaj2016.08.0249. Bibcode: 2017SSASJ..81..450M.
- Reimer R. A.; Slaten C. S.; Seapan M.; Lower M. W.; Tomlinson P. E. (1994). "Abatement of N2O emissions produced in the adipic acid industry". Environmental Progress 13 (2): 134–137. doi:10.1002/ep.670130217.
- Shimizu, A.; Tanaka, K.; Fujimori, M. (2000). "Abatement of N2O emissions produced in the adipic acid industry". Chemosphere – Global Change Science 2 (3–4): 425–434. doi:10.1016/S1465-9972(00)00024-6. Bibcode: 2000ChGCS...2..425S.
- Schneider, Lisa K.; Wüst, Anja; Pomowski, Anja; Zhang, Lin; Einsle, Oliver (2014). "Ch. 8 No Laughing Matter: The Unmaking of the Greenhouse Gas Dinitrogen Monoxide by Nitrous Oxide Reductase". in Kroneck, Peter M. H.. The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment. Metal Ions in Life Sciences. 14. Springer. pp. 177–210. doi:10.1007/978-94-017-9269-1_8. ISBN 978-94-017-9268-4.
- US Environmental Protection Agency, "Climate Change Indicators: Atmospheric Concentrations of Greenhouse Gases" Web document, accessed on 2017-02-14
- "4.1.1 Sources of Greenhouse Gases". IPCC TAR WG1 2001. http://www.grida.no/publications/other/ipcc%5Ftar/?src=/climate/ipcc_tar/wg1/247.htm.
- Crutzen, P. J.; Mosier, A. R.; Smith, K. A.; Winiwarter, W. (2008). "N2O release from agro-biofuel production negates global warming reduction by replacing fossil fuels". Atmospheric Chemistry and Physics 8 (2): 389–395. doi:10.5194/acp-8-389-2008. Bibcode: 2008ACP.....8..389C.
- "Overview of Greenhouse Gases: Nitrous Oxide Emissions". United States Environmental Protection Agency. October 6, 2016. https://19january2017snapshot.epa.gov/ghgemissions/overview-greenhouse-gases_.html.
- Grossman, Lisa (28 August 2009). "Laughing gas is biggest threat to ozone layer". New Scientist. https://www.newscientist.com/article/dn17698-laughing-gas-is-biggest-threat-to-ozone-layer.html.
- "US Nitrous Oxide Laws (alphabetically) Based on a search of online free legal databases. Conducted May 2002". Center for Cognitive Liberty and Ethics. http://www.cognitiveliberty.org/dll/N20_state_laws.htm.
- "CAL. PEN. CODE § 381b : California Code – Section 381b". Lp.findlaw.com. http://codes.lp.findlaw.com/cacode/PEN/3/1/10/s381b.
- "Lambeth Council bans laughing gas as recreational drug". BBC News. 17 August 2015. https://www.bbc.co.uk/news/uk-33955823.
- Anderton, Jim (26 June 2005). "Time's up for sham sales of laughing gas". Beehive.govt.nz. http://www.beehive.govt.nz/release/time039s-sham-sales-laughing-gas.
- "Ohio Medical". http://www.ohiomedical.com/UserFiles/File/Medical+Gas+Cylinder+Data.pdf.
- Occupational Safety and Health Guideline for Nitrous Oxide
- Paul Crutzen Interview Freeview video of Paul Crutzen Nobel Laureate for his work on decomposition of ozone talking to Harry Kroto Nobel Laureate by the Vega Science Trust.
- National Pollutant Inventory – Oxide of nitrogen fact sheet
- National Institute for Occupational Safety and Health – Nitrous Oxide
- CDC – NIOSH Pocket Guide to Chemical Hazards – Nitrous Oxide
- Nitrous Oxide FAQ
- Erowid article on Nitrous Oxide
- Nitrous oxide fingered as monster ozone slayer, Science News
- Dental Fear Central article on the use of nitrous oxide in dentistry
- Altered States Database
Original source: https://en.wikipedia.org/wiki/Nitrous oxide. Read more