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Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless
non-flammable A combustible material is something that can burn (i.e., ''combust'') in air. A combustible material is flammable if it ignites easily at ambient temperatures. In other words, a combustible material ignites with some effort and a flammable mat ...
gas Gas is one of the four fundamental states of matter (the others being solid, liquid, and plasma). A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or ...
, and has a slightly sweet scent and taste. At elevated temperatures, nitrous oxide is a powerful
oxidiser An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxid ...
similar to molecular oxygen. Nitrous oxide has significant medical uses, especially in surgery and dentistry, for its
anaesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
and pain-reducing effects. Its colloquial name, "laughing gas", coined by Humphry Davy, is due to the
euphoric Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
effects upon inhaling it, a property that has led to its
recreational use Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...
as a
dissociative Dissociatives, colloquially dissos, are a subclass of hallucinogens which distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of ...
anaesthetic. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. It is also used as an oxidiser in rocket propellants, and in motor racing to increase the power output of
engines An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy. Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power g ...
. 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 The ozone layer or ozone shield is a region of Earth's stratosphere that absorbs most of the Sun's ultraviolet radiation. It contains a high concentration of ozone (O3) in relation to other parts of the atmosphere, although still small in relat ...
, with an impact comparable to that of CFCs. Global accounting of sources and sinks over the decade ending 2016 indicates that about 40% of the average 17 TgN/yr (
teragram The kilogram (also kilogramme) is the unit of mass in the International System of Units (SI), having the unit symbol kg. It is a widely used measure in science, engineering and commerce worldwide, and is often simply called a kilo colloquially. ...
s of nitrogen per year) of emissions originated from human activity, and shows that emissions growth chiefly came from expanding
agriculture Agriculture or farming is the practice of cultivating plants and livestock. Agriculture was the key development in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that enabled people t ...
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 is used as a propellant, and has a variety of applications from rocketry to making whipped cream. It is used as a recreational drug for its potential to induce a brief "high"; most recreational users are unaware of its
neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
and potential to cause neurological damage.


Uses


Rocket motors

Nitrous oxide may be used as an
oxidiser An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxid ...
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 A hybrid-propellant rocket is a rocket with a rocket motor that uses rocket propellants in two different phases: one solid and the other either gas or liquid. The hybrid rocket concept can be traced back to the early 1930s. Hybrid rockets avo ...
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 A monopropellant rocket (or "monochemical rocket") is a rocket that uses a single chemical as its propellant. Chemical-reaction monopropellant rockets For monopropellant rockets that depend on a chemical reaction, the power for the propulsive rea ...
. In the presence of a heated catalyst, will decompose exothermically into nitrogen and oxygen, at a temperature of approximately . 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 Specific impulse (usually abbreviated ) is a measure of how efficiently a reaction mass engine (a rocket using propellant or a jet engine using fuel) creates thrust. For engines whose reaction mass is only the fuel they carry, specific impulse is ...
(''I'') of as much as 180 s. While noticeably less than the ''I'' available from hydrazine thrusters (monopropellant or
bipropellant The highest specific impulse chemical rockets use liquid propellants (liquid-propellant rockets). They can consist of a single chemical (a monopropellant) or a mix of two chemicals, called bipropellants. Bipropellants can further be divided into ...
with dinitrogen tetroxide), the decreased toxicity makes nitrous oxide an option worth investigating. Nitrous oxide is said to deflagrate at approximately at a pressure of 309 psi (21 atmospheres).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
At 600 , for example, the required ignition energy is only 6 joules, whereas 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 Engine power is the power that an engine can put out. It can be expressed in power units, most commonly kilowatt, pferdestärke (metric horsepower), or horsepower. In terms of internal combustion engines, the engine power usually describes the ' ...
. 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 In automotive engineering, an inlet manifold or intake manifold (in American English) is the part of an engine that supplies the fuel/ air mixture to the cylinders. The word ''manifold'' comes from the Old English word ''manigfeald'' (from the ...
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 World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...
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 MW 50 (Methanol-''Wasser'' 50) was a 50-50 mixture of methanol and water (German: ''Wasser'') that was often sprayed into the supercharger of World War II aircraft engines primarily for its anti-detonation effect, allowing the use of increased bo ...
, 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 () is added to prevent substance abuse.


Aerosol propellant

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 Rancidification is the process of complete or incomplete autoxidation or hydrolysis of fats and oils when exposed to air, light, moisture, or bacterial action, producing short-chain aldehydes, ketones and free fatty acids. When these processes o ...
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, 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 The Christmas season or the festive season (also known in some countries as the holiday season or the holidays) is an annually recurring period recognized in many Western and other countries that is generally considered to run from late Novemb ...
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.


Medicine

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 An anesthetic vaporizer (American English) or anaesthetic vaporiser (British English) is a device generally attached to an anesthetic machine which delivers a given concentration of a volatile anesthetic agent. It works by controlling the vap ...
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 General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced com ...
, 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 / 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 Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births glob ...
, 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. In Britain and Canada,
Entonox Nitrous oxide, is an inhaled gas used as a pain medication and together with other medications for anesthesia. Common uses include during childbirth, following trauma, and as part of end-of-life care. Onset of effect is typically within half a m ...
and Nitronox are used commonly by ambulance crews (including unregistered practitioners) as rapid and highly effective analgesic gas. 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 use

Recreational inhalation of nitrous oxide, with the purpose of causing euphoria and/or slight
hallucination A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
s, 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. 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. 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. Recreational users often misperceive nitrous oxide as a route to a "safe high", and are unaware of its potential for causing neurological damage. In Australia, recreation use became a public health concern following a rise in reported cases of neurotoxicity and a rise in emergency room admissions, and in (the state of) South Australia legislation was passed in 2020 to restrict canister sales.


Safety

Nitrous oxide is a significant
occupational hazard An occupational hazard is a hazard experienced in the workplace. This encompasses many types of hazards, including chemical hazards, biological hazards (biohazards), psychosocial hazards, and physical hazards. In the United States, the Nation ...
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 scavenger system is used to prevent a waste-gas buildup. The
National Institute for Occupational Safety and Health The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
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 A recommended exposure limit (REL) is an occupational exposure limit that has been recommended by the United States National Institute for Occupational Safety and Health. The REL is a level that NIOSH believes would be protective of worker safet ...
(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

Nitrous oxide is
neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
and long-term or habitual use can cause severe neurological damage. Like other
NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...
s, it has been suggested that produces
neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
in the form of
Olney's lesions Olney's lesions, also known as NMDA receptor antagonist neurotoxicity (NAN), are a form of potential brain damage due to drugs that have been studied experimentally and have produced neuronal damage, yet are administered by doctors to humans in the ...
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 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 charger A whipped cream charger is a steel cylinder or cartridge filled with nitrous oxide (N2O) that is used as a whipping agent in a whipped cream dispenser. The narrow end of a charger has a foil covering that is broken to release the gas. This is u ...
s (also known as "whippets" or "nangs"), which never contain oxygen, since oxygen makes cream rancid. In heavy (≥400 g or ≥200 L of gas in one session) or frequent (regular, e.g. daily or weekly) users reported to poison control centers, signs of
peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
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 Chronic toxicity, the development of adverse effects as a result of long term exposure to a contaminant or other stressor, is an important aspect of aquatic toxicology. Adverse effects associated with chronic toxicity can be directly lethal but are ...
. 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 In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate ...
.


DNA damage

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.


Oxygen deprivation

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 B deficiency

Long-term exposure to nitrous oxide may cause vitamin B deficiency. This can cause serious neurotoxicity if the user has preexisting vitamin B deficiency. It inactivates the cobalamin form of vitamin B by oxidation. Symptoms of vitamin B deficiency, including
sensory neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
, myelopathy and
encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
, may occur within days or weeks of exposure to nitrous oxide anaesthesia in people with subclinical vitamin B deficiency. Symptoms are treated with high doses of vitamin B, but recovery can be slow and incomplete. People with normal vitamin B levels have stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrous oxide abuse). Vitamin B levels should be checked in people with risk factors for vitamin B deficiency prior to using nitrous oxide anaesthesia.


Prenatal development

Several experimental studies in rats indicate that chronic exposure of pregnant females to nitrous oxide may have adverse effects on the developing fetus.


Chemical/physical risks

At room temperature () the saturated vapour pressure is 50.525 bar, rising up to 72.45 bar at —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 Hydraulic shock (colloquial: water hammer; fluid hammer) is a pressure surge or wave caused when a fluid in motion, usually a liquid but sometimes also a gas is forced to stop or change direction suddenly; a momentum change. This phenomenon com ...
"-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 In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...
of in medicine is not fully known. However, it has been shown to directly modulate a broad range of
ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
s, and this likely plays a major role in many of its effects. It moderately blocks
NMDAR The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...
and β-subunit-containing nACh channels, weakly inhibits
AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...
,
kainate Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...
, GABA and 5-HT receptors, and slightly potentiates GABA and glycine receptors. It also has been shown to activate two-pore-domain channels. While affects quite a few ion channels, its anaesthetic,
hallucinogenic Hallucinogens are a large, diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized ...
and
euphoriant Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...
effects are likely caused predominantly, or fully, via inhibition of NMDA receptor-mediated currents. In addition to its effects on ion channels, may act to imitate nitric oxide (NO) in the central nervous system, and this may be related to its analgesic and
anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
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: * Intoxication * Euphoria/dysphoria * 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.


Anxiolytic effect

In behavioural tests of anxiety, a low dose of is an effective anxiolytic, and this anti-anxiety effect is associated with enhanced activity of GABA 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 . Indeed, in humans given 30% , benzodiazepine receptor antagonists reduced the subjective reports of feeling "high", but did not alter psychomotor performance, in human clinical studies.


Analgesic effect

The analgesic effects of are linked to the interaction between the
endogenous opioid Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but t ...
system and the descending
noradrenergic Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
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 . Administration of antibodies that bind and block the activity of some endogenous opioids (not β-endorphin) also block the antinociceptive effects of . Drugs that inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of . Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of , but these drugs have no effect when injected into the spinal cord. Apart from an indirect action, nitrous oxide, like morphine also interacts directly with the endogenous opioid system by binding at opioid receptor binding sites. Conversely, α-adrenoceptor antagonists block the pain-reducing effects of when given directly to the spinal cord, but not when applied directly to the brain. Indeed, α-adrenoceptor knockout mice or animals depleted in norepinephrine are nearly completely resistant to the antinociceptive effects of . Apparently -induced release of endogenous opioids causes disinhibition of brainstem noradrenergic neurons, which release norepinephrine into the spinal cord and inhibit pain signalling. Exactly how 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. Nitrous oxide supports combustion by releasing the dipolar bonded oxygen radical, and can thus relight a glowing splint. is inert at room temperature and has few reactions. At elevated temperatures, its reactivity increases. For example, nitrous oxide reacts with at to give : : 2 + → + NaOH + The above reaction is the route adopted by the commercial chemical industry to produce azide salts, which are used as detonators.


History

The gas was first synthesised in 1772 by English
natural philosopher Natural philosophy or philosophy of nature (from Latin ''philosophia naturalis'') is the philosophical study of physics, that is, nature and the physical universe. It was dominant before the development of modern science. From the ancient wo ...
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.


Early use

The first important use of nitrous oxide was made possible by
Thomas Beddoes Thomas Beddoes (13 April 176024 December 1808) was an English physician and scientific writer. He was born in Shifnal, Shropshire and died in Bristol fifteen years after opening his medical practice there. He was a reforming practitioner and t ...
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 Factitious airs was a term used for synthetic gases which emerged around 1670 when Robert Boyle coined the term upon isolating what is now understood to be hydrogen. ''Factitious'' means "artificial, not natural", so the term means "man-made gases ...
" (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, 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 Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), a ...
. 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. One of the earliest commercial producers in the U.S. was George Poe, cousin of the poet Edgar Allan Poe, who also was the first to liquefy the gas.


Anaesthetic use

The first time nitrous oxide was used as an anaesthetic drug in the treatment of a patient was when dentist
Horace Wells Horace Wells (January 21, 1815 – January 24, 1848) was an American dentist who pioneered the use of anesthesia in dentistry, specifically the use of nitrous oxide (or laughing gas). Early life Wells was the first of three children of H ...
, with assistance by Gardner Quincy Colton and John Mankey Riggs, demonstrated insensitivity to pain from a
dental extraction A dental extraction (also referred to as tooth extraction, exodontia, exodontics, or informally, tooth pulling) is the removal of teeth from the dental alveolus (socket) in the alveolar bone. Extractions are performed for a wide variety of reaso ...
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 Boston (), officially the City of Boston, is the state capital and most populous city of the Commonwealth of Massachusetts, as well as the cultural and financial center of the New England region of the United States. It is the 24th- mo ...
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 New York, often called New York City or NYC, is the most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the most densely populated major city in the Un ...
. 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 Consumption may refer to: *Resource consumption *Tuberculosis, an infectious disease, historically * Consumption (ecology), receipt of energy by consuming other organisms * Consumption (economics), the purchasing of newly produced goods for curren ...
, 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.


Production

Reviewing various methods of producing nitrous oxide is published.


Industrial methods

Nitrous oxide is prepared on an industrial scale by careful heating of
ammonium nitrate Ammonium nitrate is a chemical compound with the chemical formula . It is a white crystalline salt consisting of ions of ammonium and nitrate. It is highly soluble in water and hygroscopic as a solid, although it does not form hydrates. It is ...
at about 250 °C, which decomposes into nitrous oxide and water vapour. : → 2 + The addition of various phosphate salts favours formation of a purer gas at slightly lower temperatures. This reaction may be difficult to control, resulting in
detonation Detonation () is a type of combustion involving a supersonic exothermic front accelerating through a medium that eventually drives a shock front propagating directly in front of it. Detonations propagate supersonically through shock waves with s ...
.


Laboratory methods

The decomposition of ammonium nitrate is also a common laboratory method for preparing the gas. Equivalently, it can be obtained by heating a mixture of sodium nitrate and
ammonium sulfate Ammonium sulfate (American English and international scientific usage; ammonium sulphate in British English); (NH4)2SO4, is an inorganic salt with a number of commercial uses. The most common use is as a soil fertilizer. It contains 21% nitrogen a ...
: :2 + () → + 2 + 4 Another method involves the reaction of urea, nitric acid and sulfuric acid: :2 (NH)CO + 2 + → 2 + 2 + (NH)SO + 2 Direct oxidation of ammonia with a manganese dioxide-
bismuth oxide Bismuth(III) oxide is perhaps the most industrially important compound of bismuth. It is also a common starting point for bismuth chemistry. It is found naturally as the mineral bismite (monoclinic) and sphaerobismoite (tetragonal, much more rare ...
catalyst has been reported: cf.
Ostwald process The Ostwald process is a chemical process used for making nitric acid (HNO3). Wilhelm Ostwald developed the process, and he patented it in 1902. The Ostwald process is a mainstay of the modern chemical industry, and it provides the main raw materi ...
. :2 + 2 → + 3
Hydroxylammonium chloride Hydroxylammonium chloride is the hydrochloric acid salt of hydroxylamine. Hydroxylamine is a biological intermediate in nitrification (biological oxidation of ammonia with oxygen into nitrite) and in anammox (biological oxidation of nitrite and am ...
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: : + → + NaCl + 2 Treating with and HCl also has been demonstrated: :2 + 8 HCl + 4 → 5 + 4 +
Hyponitrous acid Hyponitrous acid is a chemical compound with formula or HON=NOH. It is an isomer of nitramide, H2N−NO2; and a formal dimer of azanone, HNO. Hyponitrous acid forms two series of salts, the hyponitrites containing the N=NOsup>2− anion, and t ...
decomposes to NO and water with a half-life of 16 days at 25 °C at pH 1–3.Egon Wiberg, Arnold Frederick Holleman (2001) ''Inorganic Chemistry'', Elsevier :HNO→ HO + NO


Atmospheric occurrence

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 are summarized in the following table: In October 2020 scientists published a comprehensive quantification of global 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 (containing 18.8 million tonnes of nitrogen) were entering the atmosphere each year; of which 64% were natural, and 36% due to human activity.U.S. Environmental Protection Agency (2010),
Methane and Nitrous Oxide Emissions from Natural Sources
. Report EPA 430-R-10-001.
Most of the 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%). Wetlands can also be emitters of nitrous oxide. 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%).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. 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 Nitrolic acids are organic compounds with the functional group RC(NO2)=NOH. They are prepared by the reaction of nitroalkanes with base and nitrite sources: :RCH2NO2 + HNO2 → RC(NO2)=NOH + H2O The conversion was first demonstrated by V ...
intermediate derived from nitration of cyclohexanone.


Biological processes

Natural processes that generate nitrous oxide may be classified as nitrification and denitrification. Specifically, they include: * aerobic autotrophic nitrification, the stepwise oxidation of ammonia () to nitrite () and to nitrate () * anaerobic heterotrophic denitrification, the stepwise reduction of to , nitric oxide (NO), and ultimately , where facultative anaerobe bacteria use as an electron acceptor in the respiration of organic material in the condition of insufficient oxygen () * nitrifier denitrification, which is carried out by autotrophic -oxidising bacteria and the pathway whereby ammonia () is oxidised to nitrite (), followed by the reduction of to nitric oxide (NO), and molecular nitrogen () * 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. The emission of the gas to the atmosphere is limited greatly by its consumption inside the cells, by a process catalysed by the enzyme nitrous oxide reductase.


Environmental impact


Greenhouse effect

Nitrous oxide has significant
global warming potential Global warming potential (GWP) is the heat absorbed by any greenhouse gas in the atmosphere, as a multiple of the heat that would be absorbed by the same mass of carbon dioxide (). GWP is 1 for . For other gases it depends on the gas and the time ...
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 (). However, because of its low concentration (less than 1/1,000 of that of ), its contribution to the greenhouse effect is less than one third that of carbon dioxide, and also less than
water vapour (99.9839 °C) , - , Boiling point , , - , specific gas constant , 461.5 J/( kg·K) , - , Heat of vaporization , 2.27 MJ/kg , - , Heat capacity , 1.864 kJ/(kg·K) Water vapor, water vapour or aqueous vapor is the gaseous pha ...
and methane.US Environmental Protection Agency,
Climate Change Indicators: Atmospheric Concentrations of Greenhouse Gases
Web document, accessed on 2017-02-14
On the other hand, since 38% or more of the 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
fertiliser A fertilizer (American English) or fertiliser (British English; see spelling differences) is any material of natural or synthetic origin that is applied to soil or to plant tissues to supply plant nutrients. Fertilizers may be distinct from ...
s has been seriously underestimated, most of which presumably, would come under
soil Soil, also commonly referred to as earth or dirt Dirt is an unclean matter, especially when in contact with a person's clothes, skin, or possessions. In such cases, they are said to become dirty. Common types of dirt include: * Debri ...
and
ocean The ocean (also the sea or the world ocean) is the body of salt water that covers approximately 70.8% of the surface of Earth and contains 97% of Earth's water. An ocean can also refer to any of the large bodies of water into which the wo ...
ic 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, and through the breakdown of animal manure. Approximately 79 percent of all nitrous oxide released in the United States came from nitrogen fertilization. Reduction of emissions can be a hot topic in the
politics of climate change The politics of climate change results from different perspectives on how to respond to climate change. Global warming is driven largely by the Greenhouse gas emissions, emissions of greenhouse gases due to human economic activity, especially the ...
. 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 emission was the single most important ozone-depleting emission and it was expected to remain the largest throughout the 21st century.


Legality

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 ( UK) 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. In India, transfer of nitrous oxide from bulk cylinders to smaller, more transportable E-type, 1,590-litre-capacity tanks is legal when the intended use of the gas is for medical anaesthesia.


See also

* DayCent * Fink effect *
Nitrous oxide fuel blend Nitrous oxide fuel blend propellants are a class of liquid rocket propellants that were intended in the early 2010s to be able to replace hydrazine as the standard storable rocket propellent in some applications. In nitrous-oxide fuel blends, ...


References


External links


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.

* ttps://www.cdc.gov/niosh/topics/nitrousoxide/ 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
{{DEFAULTSORT:Nitrous Oxide 5-HT3 antagonists Aerosol propellants Dissociative drugs E-number additives Euphoriants GABAA receptor positive allosteric modulators Gaseous signaling molecules General anesthetics Glycine receptor agonists Greenhouse gases Industrial gases Industrial hygiene Inhalants Nitrogen oxides Monopropellants Nicotinic antagonists Nitrogen cycle NMDA receptor antagonists Rocket oxidizers Trace gases World Health Organization essential medicines Neurotoxins