View source for Nitrous oxide

{{Short description|Colourless non-flammable gas}}
{{see also|Recreational use of nitrous oxide}}
{{Redirect|N2O|3=Nitrous oxide (disambiguation)|4=and|5=N2O (disambiguation)}}
{{Redirect|Laughing gas}}
{{Distinguish|text=[[nitric oxide]] ({{chem|NO}}), [[nitrogen dioxide]] ({{chem|NO|2}}), or generic nitrogen oxide pollutants [[NOx]]}}
{{Use British English|date=December 2018}}
{{Use dmy dates|date=December 2018}}
{{Chembox
| Verifiedfields = changed
| Watchedfields  = changed
| verifiedrevid  = 477162830
| ImageFile_Ref  = {{chemboximage|correct|??}}
| Name           = 
| ImageFile      = Nitrous-oxide-2D-VB.svg
| ImageName      = Nitrous oxide's canonical forms
| ImageFile1     = Nitrous-oxide-dimensions-3D-balls.png
| ImageName1     = Ball-and-stick model with bond lengths
| ImageFile2     = Nitrous-oxide-3D-vdW.png
| ImageSize2     = 150px
| ImageName2     = Space-filling model of nitrous oxide
| SystematicName = Oxodiazen-2-ium-1-ide
| IUPACName      = Nitrous oxide<ref>{{Cite web|url=https://www.degruyter.com/database/IUPAC/entry/iupac.compound.948/html|title=[Nitrous oxide]|website=Degruyter.com|access-date=24 July 2022}}</ref> ''(not recommended)''<br />Dinitrogen oxide<ref>[[IUPAC nomenclature of inorganic chemistry 2005]]. [http://old.iupac.org/publications/books/rbook/Red_Book_2005.pdf PDF], p. 317.</ref> ''(alternative name)''
| OtherNames     = Laughing gas, sweet air, nitrous, nos, protoxide of nitrogen, hyponitrous oxide, dinitrogen oxide, dinitrogen monoxide
| Section1       = {{Chembox Identifiers
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = K50XQU1029
| InChI1 = 1/N2O/c1-2-3
| InChIKey1 = GQPLMRYTRLFLPF-UHFFFAOYAP
| SMILES = N#[N+][O-]
| SMILES1 = [N-]=[N+]=O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/N2O/c1-2-3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GQPLMRYTRLFLPF-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 10024-97-2
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 923
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1234579
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB06690
| PubChem = 948
| InChI = 1/N2O/c1-2-3
| UNNumber = 1070 (compressed)<br />2201 (liquid)
| RTECS = QX1350000
| MeSHName =
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17045
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00102
| Beilstein = 8137358
| Gmelin = 2153410
 }}
| Section2       = {{Chembox Properties
| Formula = {{chem|N|2|O}}
| MolarMass = 44.013 g/mol
| Appearance = colourless gas
| Density = 1.977 g/L (gas)
| MeltingPtC = −90.86
| MeltingPt_notes =
| BoilingPtC = −88.48
| BoilingPt_notes =
| Solubility = 1.5 g/L (15 °C)
| SolubleOther = soluble in [[ethanol|alcohol]], [[diethyl ether|ether]], [[sulfuric acid]]
| LogP = 0.35
| RefractIndex = 1.000516 (0 °C, 101.325 kPa)
| Viscosity = 14.90 μPa·s<ref name="TakahashiShibasaki-Kitakawa1996">{{cite journal|last1=Takahashi|first1=Mitsuo|last2=Shibasaki-Kitakawa|first2=Naomi|last3=Yokoyama|first3=Chiaki|last4=Takahashi|first4=Shinji|title=Viscosity of Gaseous Nitrous Oxide from 298.15 K to 398.15 K at Pressures up to 25 MPa|journal=Journal of Chemical & Engineering Data|volume=41|issue=6|year=1996|pages=1495–1498|issn=0021-9568|doi=10.1021/je960060d}}</ref>
| VaporPressure = 5150 kPa (20 °C)
| HenryConstant =
| AtmosphericOHRateConstant =
| MagSus = −18.9·10<sup>−6</sup> cm<sup>3</sup>/mol
 }}
| Section3       = {{Chembox Structure
| MolShape = linear, ''C''{{ssub|∞v}}
| Dipole = 0.166 [[Debye|D]]
 }}
| Section4       = 
| Section5       = {{Chembox Thermochemistry
| DeltaHf = +82.05 kJ/mol
| Entropy = 219.96 J/(K·mol)
 }}
| Section6       = {{Chembox Pharmacology
| ATCCode_prefix = N01
| ATCCode_suffix = AX13
| AdminRoutes = [[Inhalation]]
| Bioavail =
| Metabolism = 0.004%
| HalfLife = 5 minutes
| ProteinBound =
| Excretion = [[Respiratory]]
| Legal_status = <!-- All U.S. states except for [[California]] allow nitrous oxide as an [[anaesthetic]]. Also used in the [[United Kingdom]] and [[Australia]]. -->
| Legal_US =
| Legal_US_comment =
| Legal_UK =
| Legal_AU =
| Legal_CA =
| Pregnancy_category =
| Pregnancy_AU =
 }}
| Section7       = {{Chembox Hazards
| ExternalSDS = [http://www.inchem.org/documents/icsc/icsc/eics0067.htm Ilo.org], ICSC 0067
| GHSPictograms = {{GHS gas cylinder}} {{GHS flame over circle}}
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|270|280|281}}
| PPhrases = {{P-phrases|220|244|282|336|317|370+376|403|410+403}}
| MainHazards =
| NFPA-H = 2
| NFPA-F = 0
| NFPA-R = 0
| NFPA-S = OX
| FlashPt = Nonflammable
| LD50 =
| PEL =
 }}
| Section8       = {{Chembox Related
| OtherFunction = [[Nitric oxide]]<br />[[Dinitrogen trioxide]]<br />[[Nitrogen dioxide]]<br />[[Dinitrogen tetroxide]]<br />[[Dinitrogen pentoxide]]
| OtherFunction_label = [[nitrogen]] [[oxide]]s
| OtherCompounds = [[Ammonium nitrate]]<br />[[Azide]]
 }}
}}

'''Nitrous oxide''' (dinitrogen oxide or dinitrogen monoxide), commonly known as '''laughing gas''', '''nitrous''', '''nitro''', or '''nos''',<ref>{{cite book |title=Let's review: chemistry, the physical setting |edition=3rd |first1=Albert S. |last1=Tarendash |publisher=Barron's Educational Series |year=2001 |isbn=978-0-7641-1664-3 |page=[https://archive.org/details/letsreviewchemis03edtare/page/44 44] |url=https://archive.org/details/letsreviewchemis03edtare |url-access=registration }}</ref> is a [[chemical compound]], an [[Nitrogen oxide|oxide of nitrogen]] with the [[Chemical formula|formula]] {{chem|N|2|O}}. At room temperature, it is a colourless [[Flammability#Definitions|non-flammable]] [[gas]], and has a slightly sweet scent and taste.<ref>{{Cite web |last=PubChem |title=Nitrous oxide |url=https://pubchem.ncbi.nlm.nih.gov/compound/948 |access-date=2022-03-29 |website=pubchem.ncbi.nlm.nih.gov |language=en}}</ref> At elevated temperatures, nitrous oxide is a powerful [[Oxidising agent|oxidiser]] similar to molecular oxygen.

Nitrous oxide has significant [[Nitrous oxide (medication)|medical uses]], especially in [[surgery]] and [[dentistry]], for its [[Anesthesia|anaesthetic]] and [[Analgesic|pain-reducing]] effects.<ref name="ACB 2020">{{cite journal |author1-last=Quax |author1-first=Marcel L. J. |author2-last=Van Der Steenhoven |author2-first=Timothy J. |author3-last=Bronkhorst |author3-first=Martinus W. G. A. |author4-last=Emmink |author4-first=Benjamin L. |date=July 2020 |title=Frostbite injury: An unknown risk when using nitrous oxide as a party drug |journal=Acta Chirurgica Belgica |publisher=[[Taylor & Francis]] on behalf of the Royal Belgian Society for Surgery |volume=120 |issue=1–4 |pages=140–143 |doi=10.1080/00015458.2020.1782160 |issn=0001-5458 |pmid=32543291 |s2cid=219702849}}</ref> Its colloquial name, "laughing gas", coined by [[Humphry Davy]], is due to the [[Euphoria|euphoric]] effects upon inhaling it, a property that has led to its [[Recreational use of nitrous oxide|recreational use]] as a [[Dissociative drug|dissociative]] anaesthetic.<ref name="ACB 2020"/> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | publisher = World Health Organization | location = Geneva | hdl-access=free }}</ref> It is also used as an oxidiser in [[rocket propellant]]s, and in [[auto racing|motor racing]] to increase the [[engine power|power output]] of [[petrol engine|engines]].

Nitrous oxide's atmospheric concentration reached 333&nbsp;[[Parts-per notation|parts per billion]] (ppb) in 2020, increasing at a rate of about 1&nbsp;ppb annually.<ref name="agage" /><ref name="noaaesrl" />  It is a major scavenger of [[ozone layer|stratospheric ozone]], with an impact comparable to that of [[chlorofluorocarbon|CFCs]].<ref name="sciozo"/>  Global accounting of {{chem|N|2|O}} sources and sinks over the decade ending 2016 indicates that about 40% of the average 17&nbsp;TgN/yr ([[Megatonne|teragram]]s, or million metric tons, of nitrogen per year) of emissions originated from human activity, and shows that emissions growth chiefly came from expanding [[agriculture]].<ref name="HTian">{{cite journal |last1=Tian |first1=Hanqin |last2=Xu |first2=Rongting |last3=Canadell |first3=Josep G. |last4=Thompson |first4=Rona L. |last5=Winiwarter |first5=Wilfried |last6=Suntharalingam |first6=Parvadha |last7=Davidson |first7=Eric A. |last8=Ciais |first8=Philippe |last9=Jackson |first9=Robert B. |last10=Janssens-Maenhout |first10=Greet |display-authors=et al. |date=October 2020 |title=A comprehensive quantification of global nitrous oxide sources and sinks |url=https://www.nature.com/articles/s41586-020-2780-0 |url-status=bot: unknown |journal=Nature |language=en |volume=586 |issue=7828 |pages=248–256 |bibcode=2020Natur.586..248T |doi=10.1038/s41586-020-2780-0 |issn=1476-4687 |pmid=33028999 |hdl=1871.1/c74d4b68-ecf4-4c6d-890d-a1d0aaef01c9 |s2cid=222217027 |archive-url=https://web.archive.org/web/20201203131716/https://www.nature.com/articles/s41586-020-2780-0 |archive-date=3 December 2020 |access-date=2020-11-09|hdl-access=free }}</ref><ref>{{cite journal |author=Thompson, R. L. |author2=Lassaletta, L. |author3=Patra, P. K. |display-authors=et al. |title=Acceleration of global N<sub>2</sub>O emissions seen from two decades of atmospheric inversion |journal=Nat. Clim. Change |year=2019 |volume=9 |issue=12 |pages=993–998 |doi=10.1038/s41558-019-0613-7|bibcode=2019NatCC...9..993T |s2cid=208302708 |url=http://pure.iiasa.ac.at/id/eprint/16173/2/N2O_paper_SI_revision2_v1.docx}}</ref>  Being the third most important [[greenhouse gas]], nitrous oxide also substantially contributes to [[global warming]].<ref name="ipccar5">{{cite book |url=https://www.ipcc.ch/report/ar5/wg1/ |contribution= Chapter 8 |title=AR5 Climate Change 2013: The Physical Science Basis |pages=677–678}}</ref><ref name="physorg">{{cite news |title=Nitrous oxide emissions pose an increasing climate threat, study finds |language=en |work=phys.org |url=https://phys.org/news/2020-10-nitrous-oxide-emissions-pose-climate.html |access-date=2020-11-09}}</ref>

Nitrous oxide is used as a [[propellent|propellant]], and has a variety of applications from [[Rocket|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]] and potential to cause neurological damage.<ref name=nangs/>

==Uses==

===Rocket motors===
Nitrous oxide may be used as an [[oxidizing agent|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 temperatures) enable it to be highly competitive with stored high-pressure gas systems.<ref>{{cite web|author=Berger, Bruno |date=5 October 2007 |url=http://www.spl.ch/publication/SPL_Papers/N2O_safety_e.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.spl.ch/publication/SPL_Papers/N2O_safety_e.pdf |archive-date=2022-10-09 |url-status=live |title=Is nitrous oxide safe? |publisher=Swiss Propulsion Laboratory |pages=1–2 |quote=...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] N{{ssub|2}}O is a monopropellant (as H{{ssub|2}}O{{ssub|2}} or Hydrazine...)}}</ref>

In a 1914 patent, American rocket pioneer [[Robert Goddard]] suggested nitrous oxide and gasoline as possible propellants for a liquid-fuelled rocket.<ref>Goddard, R. H. (1914) "Rocket apparatus" {{US patent|1103503}}</ref> 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 rocketry|amateur]] and [[high power rocket]]ry with various plastics as the fuel.

Nitrous oxide also may be used in a [[monopropellant rocket]]. In the presence of a heated [[catalyst]], {{chem|N|2|O}} will decompose exothermically into nitrogen and oxygen, at a temperature of approximately {{convert|1070|F}}.<ref>[http://spg-corp.com/nitrous-oxide-safety.html Nitrous Oxide Safety]. Space Propulsion Group (2012)</ref> 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]] (''I''{{ssub|sp}}) of as much as 180 s. While noticeably less than the ''I''{{ssub|sp}} available from [[hydrazine]] thrusters (monopropellant or [[Bipropellant rocket|bipropellant]] with [[dinitrogen tetroxide]]), the decreased toxicity makes nitrous oxide an option worth investigating.

Nitrous oxide is said to [[deflagration|deflagrate]] at approximately {{convert|600|C}} at a pressure of 309&nbsp;psi (21&nbsp;atmospheres).<ref name="Munke">Munke, Konrad (2 July 2001) [http://hobbyspace.com/AAdmin/archive/SpecialTopics/Misc/eindhoven.pdf Nitrous Oxide Trailer Rupture], Report at CGA Seminar "Safety and Reliability of Industrial Gases, Equipment and Facilities", 15–17 October 2001, St. Louis, Missouri</ref> At 600&nbsp;{{abbr|psi|pounds per square inch}}, for example, the required ignition energy is only 6&nbsp;joules, whereas {{chem|N|2|O}} at 130&nbsp;psi a 2,500-joule ignition energy input is insufficient.<ref>{{cite web|url=http://www.scaled.com/images/uploads/news/N2OSafetyGuidelines.pdf |title=Scaled Composites Safety Guidelines for {{chem|N|2|O}} |publisher=Scaled Composites |date=17 June 2009 |archive-url=https://web.archive.org/web/20110712044612/http://www.scaled.com/images/uploads/news/N2OSafetyGuidelines.pdf |access-date=29 December 2013 |archive-date=12 July 2011 |quote=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.}}</ref><ref>[http://hobbyspace.com/AAdmin/archive/SpecialTopics/Misc/pratt-explosion.pdf FR-5904]. Pratt & Whitney Aircraft.</ref>

===Internal combustion engine===
{{Main|Nitrous oxide engine}}

In vehicle [[racing]], nitrous oxide (often called "[[Nitrous oxide engine|nitrous]]") allows the engine to burn more fuel by providing more oxygen during combustion. The increase in oxygen allows 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 [[heat of vaporization|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 engine]]s. 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]], [[schnellbomber|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 (engine)|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 type of operation. It is important with nitrous oxide augmentation of [[petrol engine]]s to maintain proper [[operating temperature]]s and fuel levels to prevent "[[pre-ignition]]",<ref>Cline, Allen W. (January 2000) [http://www.contactmagazine.com/Issue54/EngineBasics.html "Engine Basics: Detonation and Pre-Ignition"]. ''CONTACT!'' Magazine</ref> 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 pistons or valves. It also may crack or warp the piston or cylinder 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]] ({{chem|SO|2}}) is added to prevent substance abuse.<ref name="Automotive gas">{{cite web|url=https://www.holley.com/support/faq/?category=NOS |work=Holley |title=Holley performance products, FAQ for Nitrous Oxide Systems |access-date=18 December 2013}}</ref>

===Aerosol propellant===
[[File:N2O whippets.jpg|thumb|right|Food-grade {{chem|N|2|O}} [[whipped-cream charger]]s]]
The gas is approved for use as a [[food additive]] ([[E number|E&nbsp;number]]: E942), specifically as an [[Aerosol spray#Aerosol propellants|aerosol spray propellant]]. Its most common uses in this context are in aerosol [[whipped cream]] canisters and [[cooking spray]]s.

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, and will return to a more liquid state within half an hour to one hour.<ref>{{Cite web|url=http://www.explora-science.net/nitrousoxide-use-as-a-propellant-and-in-cooking/|title=Explora Science {{!}} Nitrous use as a propellant and in cooking|language=en-US|access-date=2019-02-19|archive-date=27 February 2019|archive-url=https://web.archive.org/web/20190227015310/http://www.explora-science.net/nitrousoxide-use-as-a-propellant-and-in-cooking/}}</ref> Thus, the method is not suitable for decorating food that will not be served immediately.

In 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.<ref>{{cite news |last=Dewey |first=Caitlin |url=https://www.washingtonpost.com/news/wonk/wp/2016/12/21/the-real-reason-you-cant-buy-whipped-cream-this-christmas/ |title=The real reason grocery stores are running out of whipped cream this Christmas |newspaper=[[The Washington Post]] |date=2016-12-21 |access-date=2016-12-22 }}</ref>

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 [[ethanol|alcohol]] and [[propane]].

===Medicine===
{{Main|Nitrous oxide (medication)}}
[[File:N2O Medical Tanks.jpg|thumb|right|upright|Medical-grade {{chem|N|2|O}} tanks used in [[dentistry]]]]

Nitrous oxide has been used in dentistry and surgery, as an anaesthetic and analgesic, since 1844.<ref name="Drug discovery">{{cite book|url=https://books.google.com/books?id=mYQxRY9umjcC |author=Sneader W |title=Drug Discovery –A History |chapter=Systematic Medicine |pages=74–87 |date=2005 |publisher=John Wiley and Sons |isbn=978-0-471-89980-8}}</ref> In the early days, the gas was administered through simple inhalers consisting of a breathing bag made of rubber cloth.<ref name="use in dentistry">{{cite journal|author=Miller AH |title=Technical Development of Gas Anesthesia |journal=Anesthesiology |volume=2 |issue=4 |pages=398–409 |year=1941 |doi=10.1097/00000542-194107000-00004|s2cid=71117361 |doi-access=free }}</ref> 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 and oxygen|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 can increase the risk of postoperative nausea and vomiting.<ref>{{Cite journal|last1=Divatia|first1=Jigeeshu V.|last2=Vaidya|first2=Jayant S.|last3=Badwe|first3=Rajendra A.|last4=Hawaldar|first4=Rohini W.|title=Omission of Nitrous Oxide during Anesthesia Reduces the Incidence of Postoperative Nausea and Vomiting|journal=Anesthesiology|volume=85|issue=5|pages=1055–1062|doi=10.1097/00000542-199611000-00014|pmid=8916823|year=1996|s2cid=41549796|url=https://semanticscholar.org/paper/a845666e10d59515e6f6b3c524486cd501af9b80}}</ref><ref>{{Cite journal|last=Hartung|first=John|title=Twenty-Four of Twenty-Seven Studies Show a Greater Incidence of Emesis Associated with Nitrous Oxide than with Alternative Anesthetics|journal=Anesthesia & Analgesia|volume=83|issue=1|pages=114–116|doi=10.1213/00000539-199607000-00020|year=1996}}</ref><ref>{{Cite journal|last1=Tramèr|first1=M.|last2=Moore|first2=A.|last3=McQuay|first3=H.|date=February 1996|title=Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials|journal=British Journal of Anaesthesia|volume=76|issue=2|pages=186–193|pmid=8777095|doi=10.1093/bja/76.2.186|doi-access=free}}</ref>

Dentists use a simpler machine which only delivers an {{chem|N|2|O}}/{{chem|O|2}} mixture for the patient to inhale while conscious but must still be a recognised purpose designed dedicated relative analgesic flowmeter with a minimum 30% of oxygen at all times and a maximum upper limit of 70% nitrous oxide. The patient is kept conscious throughout the procedure, and retains adequate mental faculties to respond to questions and instructions from the dentist.<ref>{{Cite journal|last=Council on Clinical Affairs|date=2013|title=Guideline on use of nitrous oxide for pediatric dental patients|url=http://www.aapd.org/media/policies_guidelines/g_nitrous.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.aapd.org/media/policies_guidelines/g_nitrous.pdf |archive-date=2022-10-09 |url-status=live|journal=Reference Manual V37|volume=6|pages=206–210}}</ref>

Inhalation of nitrous oxide is used frequently to relieve pain associated with [[childbirth]], [[Physical trauma|trauma]], [[dentistry|oral surgery]] and [[acute coronary syndrome]] (including heart attacks). Its use during labour has been shown to be a safe and effective aid for birthing women.<ref>{{cite web |last=Copeland |first=Claudia |url=http://www.pregnancy.org/article/nitrous-oxide-analgesia-child-birth |title=Nitrous Oxide Analgesia for Childbirth |website=Pregnancy.org  |archive-url=https://web.archive.org/web/20110525080809/http://www.pregnancy.org/article/nitrous-oxide-analgesia-child-birth |archive-date=25 May 2011 }}</ref> Its use for acute coronary syndrome is of unknown benefit.<ref name="AHA10">{{cite journal|author=O'Connor RE |title=Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care |journal=Circulation |volume=122 |issue=18 Suppl 3 |pages=S787–817 |year=2010 |pmid=20956226 |doi=10.1161/CIRCULATIONAHA.110.971028 |author2=Brady W |author3=Brooks SC |last4=Diercks |first4=D. |last5=Egan |first5=J. |last6=Ghaemmaghami |first6=C. |last7=Menon |first7=V. |last8=O'Neil |first8=B. J. |last9=Travers |first9=A. H. |last10=Yannopoulos |display-authors=8 |doi-access=free }}</ref>

In Britain and Canada, [[Nitrous oxide (medication)|Entonox]] 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.<ref>{{Cite journal|last1=Faddy|first1=S. C.|last2=Garlick|first2=S. R.|date=2005-12-01|title=A systematic review of the safety of analgesia with 50% nitrous oxide: can lay responders use analgesic gases in the prehospital setting?|journal=Emergency Medicine Journal|volume=22|issue=12|pages=901–908|doi=10.1136/emj.2004.020891|pmc=1726638|pmid=16299211}}</ref>

===Recreational use===
{{main|Recreational use of nitrous oxide}}
[[File:Doctor and Mrs Syntax, with a party of friends, experimentin Wellcome L0022227.jpg|thumb|[[Aquatint]] depiction of a laughing gas party in the nineteenth century, by [[Thomas Rowlandson]]]]
[[File:Ban of Nitrous oxide use.jpg|thumb|Street sign indicating ban of nitrous oxide use near the Poelestraat in [[Groningen]]]]
[[File:Nitrous oxide whippits used recreationally as a drug by Dutch youngsters near a school, Utrecht, 2017 - 1.jpg|thumb|[[Whipped-cream charger|Whippit]] remnants (the small steel canisters) of recreational drug use, the Netherlands, 2017]]

[[recreational use of nitrous oxide|Recreational inhalation of nitrous oxide]], with the purpose of causing [[euphoria (emotion)|euphoria]] and/or slight [[hallucination]]s, began as a phenomenon for the British upper class in 1799, known as "laughing gas parties".<ref>{{Cite book|last=Davy|first=Humphry|url=http://archive.org/details/researcheschemic00davy|title=Researches, chemical and philosophical: chiefly concerning nitrous oxide, or diphlogisticated nitrous air, and its respiration|date=1800|publisher=London : printed for J. Johnson, St. Paul's Church-Yard, by Biggs and Cottle, Bristol|others=Francis A. Countway Library of Medicine}}</ref>

Starting in the 19th century, the widespread availability of the gas for medical and culinary purposes allowed for recreational use to expand greatly globally. In the UK as of 2014, nitrous oxide was estimated to be used by almost half a million young people at nightspots, festivals and parties.<ref>{{cite news | title = Warning over laughing gas misuse | url = https://www.theguardian.com/politics/2014/aug/09/warning-over-laughing-gas-misuse | date = 9 August 2014 | work = [[The Guardian]] |location=London |agency=[[Press Association]] | access-date = 9 August 2014}}</ref>

Widespread recreational use of the drug throughout the UK was featured in the 2017 [[Vice Media|Vice]] documentary ''Inside The Laughing Gas Black Market'', in which journalist [[Matt Shea (documentary filmmaker)|Matt Shea]] met with dealers of the drug who stole it from hospitals.<ref>{{Citation|last=VICE|title=Inside The Laughing Gas Black Market|date=2017-02-07|url=https://www.youtube.com/watch?v=gdhdAktIHtg| archive-url=https://ghostarchive.org/varchive/youtube/20211029/gdhdAktIHtg| archive-date=2021-10-29|access-date=2019-03-29}}{{cbignore}}</ref>

A significant issue cited in London's press is the effect of nitrous oxide canister littering, which is highly visible and causes significant complaints from communities.<ref>{{Cite web|url=https://metro.co.uk/2018/07/10/recycling-used-laughing-gas-canisters-for-cash-could-help-create-a-cleaner-britain-7694925/|title=Recycling used laughing gas canisters for cash could help create a cleaner Britain|date=2018-07-10|website=Metro|language=en-US|access-date=2019-07-15}}</ref>

While casual use of nitrous oxide is understood by most recreational users to be a route to a "safe high", many are unaware that excessive consumption has the potential to cause neurological harm which, if left untreated, can result in permanent neurological damage.<ref>{{cite news |title=Nitrous oxide: Laughing gas users risk spine damage, say doctors |url=https://www.bbc.co.uk/news/health-64718233 |access-date=26 March 2023}}</ref> 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.<ref name=nangs/>

==Safety==

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 (architecture)|ventilation system]] or {{chem|N|2|O}} [[scavenger system]] is used to prevent a waste-gas buildup.{{cn|date=August 2022}}

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.<ref>[https://www.cdc.gov/niosh/docs/94-100/ 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</ref> It set a [[recommended exposure limit]] (REL) of 25 [[Parts-per notation|ppm]] (46&nbsp;mg/m<sup>3</sup>) to escaped anaesthetic.<ref>{{Cite web|title =NIOSH Pocket Guide to Chemical Hazards – Nitrous oxide|url = https://www.cdc.gov/niosh/npg/npgd0465.html|website = CDC|access-date = 2015-11-21}}</ref>

===Mental and manual impairment===
Exposure to nitrous oxide causes short-term decreases in mental performance, audiovisual ability and manual dexterity.<ref>[https://www.cdc.gov/niosh/docs/1970/77-140.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.</ref> These effects coupled with the induced spatial and temporal disorientation could result in physical harm to the user from environmental hazards.<ref name="Mike Jay 22–25"/>

===Neurotoxicity and neuroprotection===
Nitrous oxide is [[neurotoxic]] and there is evidence that medium or long-term habitual consumption of significant quantities can cause neurological harm with the potential for permanent damage if left untreated.<ref name=nangs>{{cite journal |vauthors=Evans EB, Evans MR |title=Nangs, balloons and crackers: Recreational nitrous oxide neurotoxicity |journal=Aust J Gen Pract |volume=50 |issue=11 |pages=834–838 |date=November 2021 |pmid=34713284 |doi=10.31128/AJGP-10-20-5668 |s2cid=240153502 |type=Review|doi-access=free }}</ref><ref>{{cite news |title=Nitrous oxide: Laughing gas users risk spine damage, say doctors |url=https://www.bbc.co.uk/news/health-64718233 |access-date=26 March 2023}}</ref>

Like other [[NMDA receptor antagonist]]s, it has been suggested that {{chem|N|2|O}} produces [[neurotoxicity]] in the form of [[Olney's lesions]] in rodents upon prolonged (several hour) exposure.<ref name="pmid14622904">{{cite journal |year=2003|title=Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain|journal=Neuroscience|volume=122|issue=3|pages=609–16|doi=10.1016/j.neuroscience.2003.07.012|pmid=14622904|vauthors=Jevtovic-Todorovic V, Beals J, Benshoff N, Olney JW|s2cid=9407096|url=https://www.semanticscholar.org/paper/278210b62f0dd2ee8cafd9136bac010d8ade00e1}}</ref><ref name="pmid12854473">{{cite journal|year=2003|title=NMDA receptor antagonist neurotoxicity and psychotomimetic activity|journal=Masui. The Japanese Journal of Anesthesiology|language=ja|volume=52|issue=6|pages=594–602|pmid=12854473|vauthors=Nakao S, Nagata A, Masuzawa M, Miyamoto E, Yamada M, Nishizawa N, Shingu K}}</ref><ref name="pmid10928976">{{cite journal |year=2000|title=Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats|journal=British Journal of Pharmacology|volume=130|issue=7|pages=1692–8|doi=10.1038/sj.bjp.0703479|pmc=1572233|pmid=10928976 |vauthors=Jevtovic-Todorovic V, Benshoff N, Olney JW}}</ref><ref name="pmid15718054">{{cite journal|last2=Carter|year=2005|title=The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to young rat brain|journal=Neurobiology of Aging|volume=26|issue=6|pages=947–56|doi=10.1016/j.neurobiolaging.2004.07.009|pmid=15718054|author=Jevtovic-Todorovic V, Carter LB|s2cid=25095727|url=https://www.semanticscholar.org/paper/c282c0078f2129a86d3875a758c8c23b46332df0}}</ref>
It has been argued that, because {{chem|N|2|O}} is rapidly expelled from the body under normal circumstances, it is less likely to be neurotoxic than other NMDAR antagonists.<ref name="pmid16179534">{{cite journal |year=2005|title=Potentially neuroprotective and therapeutic properties of nitrous oxide and xenon|journal=Annals of the New York Academy of Sciences|volume=1053|issue=1|pages=289–300|bibcode=2005NYASA1053..289A|doi=10.1111/j.1749-6632.2005.tb00036.x|pmid=16179534 |vauthors=Abraini JH, David HN, Lemaire M|s2cid=34160112}}</ref> 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.<ref name="pmid14622904" /> Nitrous oxide also may cause neurotoxicity after extended exposure because of [[hypoxia (medical)|hypoxia]]. This is especially true of non-medical formulations such as [[whipped-cream charger]]s (also known as "whippets" or "nangs"),<ref>{{cite journal|pmid=23801743|doi=10.1093/bja/aet215|year=2013|last1=De Vasconcellos|first1=K.|title=Nitrous oxide: Are we still in equipoise? A qualitative review of current controversies|journal=British Journal of Anaesthesia|volume=111|issue=6|pages=877–85|last2=Sneyd|first2=J. R.|doi-access=free}}</ref> which never contain oxygen, since oxygen makes cream rancid.<ref name="Middleton 2012 p.">{{cite book|title=Physics in anaesthesia|last=Middleton|first=Ben|publisher=Scion Pub. Ltd|year=2012|isbn=978-1-904842-98-9|location=Banbury, Oxfordshire, UK}}</ref>

In heavy (≥400 g or ≥200 L of {{N2O}} gas in one session) or frequent (regular, i.e., 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]].<ref>{{cite journal|doi=10.1016/j.drugpo.2021.103519|year=2022|last1=van Riel|first1=A.J.H.P.|title=Alarming increase in poisonings from recreational nitrous oxide use after a change in EU-legislation, inquiries to the Dutch Poisons Information Center|journal=International Journal of Drug Policy|volume=100|page=103519|pmid=34753046|doi-access=free}}</ref>

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 Ca<sup>2+</sup> influx in neuronal cell cultures, a critical event involved in [[excitotoxicity]].<ref name="pmid16179534" />

===DNA damage===
Occupational exposure to ambient nitrous oxide has been associated with DNA damage, due to interruptions in DNA synthesis.<ref>{{cite web |last1=Randhawa |first1=G. |last2=Bodenham |first2=A. |title=The increasing recreational use of nitrous oxide: history revisited |url=https://academic.oup.com/bja/article/116/3/321/2566058 |journal=British Journal of Anaesthesia |volume=116 |issue=3 |pages=321–324 |language=en |doi=10.1093/bja/aev297 |pmid=26323292 |date=1 March 2016}}</ref> This correlation is dose-dependent<ref>{{cite journal |last1=Wrońska-Nofer |first1=Teresa |last2=Nofer |first2=Jerzy-Roch |last3=Jajte |first3=Jolanta |last4=Dziubałtowska |first4=Elżbieta |last5=Szymczak |first5=Wiesław |last6=Krajewski |first6=Wojciech |last7=Wąsowicz |first7=Wojciech |last8=Rydzyński |first8=Konrad |title=Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N<sub>2</sub>O) |journal=Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis |date=1 March 2012 |volume=731 |issue=1 |pages=58–63 |doi=10.1016/j.mrfmmm.2011.10.010 |pmid=22085808 }}</ref><ref>{{cite journal |title=DNA damage induced by nitrous oxide: Study in medical personnel of operating rooms |journal=Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis |date=18 June 2009 |volume=666 |issue=1–2 |pages=39–43 |doi=10.1016/j.mrfmmm.2009.03.012 |pmid=19439331 |last1=Wrońska-Nofer |first1=Teresa |last2=Palus |first2=Jadwiga |last3=Krajewski |first3=Wojciech |last4=Jajte |first4=Jolanta |last5=Kucharska |first5=Małgorzata |last6=Stetkiewicz |first6=Jan |last7=Wąsowicz |first7=Wojciech |last8=Rydzyński |first8=Konrad }}</ref> 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, oxygen deprivation can occur, resulting in low 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.<ref>[http://justsayn2o.com/nitrous.dangers.html#oxygendep Dangers of Nitrous Oxide]. Just Say N2O</ref> 

===Vitamin B{{ssub|12}} deficiency===

Long-term exposure to nitrous oxide may cause [[Vitamin B12 deficiency|vitamin B{{ssub|12}} deficiency]].  This can cause serious neurotoxicity if the user has preexisting vitamin B{{ssub|12}} deficiency.<ref>{{Cite journal|last2=Holder|first2=W. D. Jr.|year=1993|title=Neurologic Degeneration Associated with Nitrous Oxide Anesthesia in Patients with Vitamin B12 Deficiency|journal=Archives of Surgery|volume=128|issue=12|pages=1391–5|doi=10.1001/archsurg.1993.01420240099018|pmid=8250714|last1=Flippo|first1=T. S.}}</ref> It inactivates the cobalamin form of vitamin B{{ssub|12}} by oxidation. Symptoms of vitamin B{{ssub|12}} deficiency, including [[Peripheral neuropathy|sensory neuropathy]], [[myelopathy]] and [[encephalopathy]], may occur within days or weeks of exposure to nitrous oxide anaesthesia in people with subclinical vitamin B{{ssub|12}} deficiency.

Symptoms are treated with high doses of vitamin B{{ssub|12}}, but recovery can be slow and incomplete.<ref>{{cite book |last=Giannini |first=A.J. |year=1999 |title=Drug Abuse |place=Los Angeles |publisher=Health Information Press |isbn=978-1-885987-11-2 |url-access=registration |url=https://archive.org/details/drugabuse00ajam }}</ref>

People with normal vitamin B{{ssub|12}} levels have stores to make the effects of nitrous oxide insignificant, unless exposure is repeated and prolonged (nitrous oxide abuse). Vitamin B{{ssub|12}} levels should be checked in people with risk factors for vitamin B{{ssub|12}} deficiency prior to using nitrous oxide anaesthesia.<ref>{{Cite web |last=Conrad |first=Marcel |title=Pernicious Anemia |website=Medscape |date=4 October 2006 |url=http://www.emedicine.com/med/topic1799.htm |access-date=2 June 2008}}</ref>

===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.<ref name="Vieira1980">{{cite journal|pmid=7189346 |year=1980 |last1=Vieira |first1=E. |last2=Cleaton-Jones |first2=P. |last3=Austin |first3=J.C. |last4=Moyes |first4=D.G. |last5=Shaw |first5=R. |title=Effects of low concentrations of nitrous oxide on rat fetuses |volume=59 |issue=3 |pages=175–7 |journal=Anesthesia and Analgesia |doi=10.1213/00000539-198003000-00002|s2cid=41966990 |doi-access=free }}</ref><ref>{{cite journal|pmid=465253 |year=1979 |last1=Vieira |first1=E. |title=Effect of the chronic administration of nitrous oxide 0.5% to gravid rats |volume=51 |issue=4 |pages=283–7 |journal=British Journal of Anaesthesia |doi=10.1093/bja/51.4.283|doi-access=free }}</ref><ref>{{cite journal|pmid=6821624 |year=1983 |last1=Vieira |first1=E |last2=Cleaton-Jones |first2=P |last3=Moyes |first3=D. |title=Effects of low intermittent concentrations of nitrous oxide on the developing rat fetus |volume=55 |issue=1 |pages=67–9 |journal=British Journal of Anaesthesia |doi=10.1093/bja/55.1.67|doi-access=free }}</ref>

===Chemical/physical risks===
At room temperature ({{Convert|20|C|disp=sqbr}}) the saturated vapour pressure is 50.525 bar, rising up to 72.45&nbsp;bar at {{convert|36.4|C}}—the [[Critical point (thermodynamics)|critical temperature]]. The pressure curve is thus unusually sensitive to temperature.<ref>[http://encyclopedia.airliquide.com/encyclopedia.asp?LanguageID=11&CountryID=19&Formula=&GasID=55&UNNumber= Nitrous oxide] {{Webarchive|url=https://web.archive.org/web/20160330004038/http://encyclopedia.airliquide.com/encyclopedia.asp?LanguageID=11&CountryID=19&Formula=&GasID=55&UNNumber= |date=30 March 2016 }}. Air Liquide Gas Encyclopedia.</ref>

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).<ref>{{cite web|url=http://www.ukrocketman.com/rocketry/hybridukhistory.shtml |title=Vaseline triggered explosion of hybrid rocket |publisher=Ukrocketman.com}}</ref> 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.<ref>{{cite web|url=http://www.airproducts.com/nr/rdonlyres/8c46596e-2f7d-4895-b12a-e54cd63e1996/0/safetygram20.pdf |archive-url=https://web.archive.org/web/20060901093045/http://www.airproducts.com/nr/rdonlyres/8c46596e-2f7d-4895-b12a-e54cd63e1996/0/safetygram20.pdf |archive-date=1 September 2006 |title=Safetygram 20: Nitrous Oxide |publisher=Airproducts.com}}</ref>

There also have been incidents where nitrous oxide decomposition in plumbing has led to the explosion of large tanks.<ref name="Munke" />

==Mechanism of action==
The pharmacological [[mechanism of action]] of {{chem|N|2|O}} in medicine is not fully known. However, it has been shown to directly modulate a broad range of [[ligand-gated ion channel]]s, and this likely plays a major role in many of its effects. It moderately blocks [[NMDA receptor|NMDAR]] and [[CHRNB2|β{{ssub|2}}-subunit]]-containing [[nicotinic acetylcholine receptor|nACh channels]], weakly inhibits [[AMPA receptor|AMPA]], [[kainate receptor|kainate]], [[GABAA-rho receptor|GABA{{ssub|C}}]] and [[5-HT3 receptor|5-HT{{ssub|3}} receptors]], and slightly potentiates [[GABAA receptor|GABA{{ssub|A}}]] and [[glycine receptor]]s.<ref name="pmid11020766">{{cite journal|vauthors=Yamakura T, Harris RA |title=Effects of gaseous anaesthetics nitrous oxide and xenon on ligand-gated ion channels. Comparison with isoflurane and ethanol |journal=Anesthesiology |volume=93 |issue=4 |pages=1095–101 |year=2000 |pmid=11020766 |doi=10.1097/00000542-200010000-00034|s2cid=4684919 }}</ref><ref name="pmid9822732">{{cite journal |vauthors=Mennerick S, Jevtovic-Todorovic V, Todorovic SM, Shen W, Olney JW, Zorumski CF |title=Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures |journal=Journal of Neuroscience |volume=18 |issue=23 |pages=9716–26 |year=1998 |pmid=9822732 |pmc=6793274 |doi=10.1523/JNEUROSCI.18-23-09716.1998 }}</ref> It also has been shown to activate [[Two-pore-domain potassium channel|two-pore-domain {{chem|K|+}} channels]].<ref name="pmid14742687">{{cite journal |vauthors=Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP |title=Two-pore-domain K<sup>+</sup> channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane |journal=Molecular Pharmacology |volume=65 |issue=2 |pages=443–52 |year=2004 |pmid=14742687 |doi=10.1124/mol.65.2.443|s2cid=7762447 }}</ref> While {{chem|N|2|O}} 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.<ref name="pmid11020766" /><ref name="pmid17352529">{{cite journal|vauthors=Emmanouil DE, Quock RM |title=Advances in Understanding the Actions of Nitrous Oxide |journal=Anesthesia Progress |volume=54 |issue=1 |pages=9–18 |year=2007 |pmid=17352529 |pmc=1821130 |doi=10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2}}</ref> In addition to its effects on ion channels, {{chem|N|2|O}} may act to imitate [[nitric oxide]] (NO) in the central nervous system, and this may be related to its [[analgesic]] and [[anxiolytic]] properties.<ref name="pmid17352529" /> 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;<ref>{{Cite journal|last1=Atkinson|first1=Roland M.|last2=Green|first2=J. DeWayne|last3=Chenoweth|first3=Dennis E.|last4=Atkinson|first4=Judith Holmes|date=1979-10-01|title=Subjective Effects of Nitrous Oxide: Cognitive, Emotional, Perceptual and Transcendental Experiences|journal=Journal of Psychedelic Drugs|volume=11|issue=4|pages=317–330|doi=10.1080/02791072.1979.10471415|pmid=522172}}</ref><ref>{{Cite journal|last1=Walker|first1=Diana J.|last2=Zacny|first2=James P.|date=2001-09-01|title=Within- and between-subject variability in the reinforcing and subjective effects of nitrous oxide in healthy volunteers|journal=Drug and Alcohol Dependence|volume=64|issue=1|pages=85–96|doi=10.1016/s0376-8716(00)00234-9|pmid=11470344}}</ref> however, from his discussion, Jay (2008)<ref name="Mike Jay 22–25">{{Cite journal|vauthors=Jay M |date=2008-09-01|title=Nitrous oxide: recreational use, regulation and harm reduction|journal=Drugs and Alcohol Today|volume=8|issue=3|pages=22–25|doi=10.1108/17459265200800022}}</ref> 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.<ref name="Mike Jay 22–25"/>

===Anxiolytic effect===
In behavioural tests of [[anxiety]], a low dose of {{chem|N|2|O}} is an effective anxiolytic, and this anti-anxiety effect is associated with enhanced activity of GABA{{ssub|A}} receptors, as it is partially reversed by [[GABAA receptor|benzodiazepine receptor]] [[receptor antagonist|antagonists]]. Mirroring this, animals that have developed tolerance to the anxiolytic effects of [[benzodiazepine]]s are partially tolerant to {{chem|N|2|O}}.<ref name="emmanouil">{{cite journal|title=Nitrous oxide anxiolytic effect in mice in the elevated plus maze: mediation by benzodiazepine receptors |vauthors=Emmanouil DE, Johnson CH, Quock RM |journal=Psychopharmacology |volume=115 |issue=1–2 |pages=167–72 |year=1994 |doi=10.1007/BF02244768 |pmid=7862891|s2cid=21652496 |url=https://www.semanticscholar.org/paper/6f042c60b815a9a61d808f0913bdaa73fffcc253 }}</ref> Indeed, in humans given 30% {{chem|N|2|O}}, benzodiazepine receptor antagonists reduced the subjective reports of feeling "high", but did not alter [[psychomotor learning|psychomotor]] performance, in human clinical studies.<ref name="zacny">{{cite journal|title=Flumazenil may attenuate some subjective effects of nitrous oxide in humans: a preliminary report |vauthors=Zacny JP, Yajnik S, Coalson D, Lichtor JL, Apfelbaum JL, Rupani G, Young C, Thapar P, Klafta J |journal=Pharmacology Biochemistry and Behavior |volume=51 |issue=4 |pages=815–9 |year=1995 |doi=10.1016/0091-3057(95)00039-Y |pmid=7675863|s2cid=39068081 |url=https://www.semanticscholar.org/paper/8aa3c67fe1064a205542499b778a8a903c9151c3 }}</ref><ref>{{Cite journal |last=Gillman |first=Mark Akfred |date=2022 |title=What is better for psychiatry: Titrated or fixed concentrations of nitrous oxide? |journal=Front. Psychiatry |volume=13 |issue=773190 |pages=460–3|doi=10.3389/fpsyt.2022.773190 |pmid=36072452 |pmc=9441863 |doi-access=free }}</ref>

===Analgesic effect===
The analgesic effects of {{chem|N|2|O}} are linked to the interaction between the [[Opioid#Endogenous opioids|endogenous opioid]] system and the descending [[Norepinephrine|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 {{chem|N|2|O}}.<ref>{{cite journal|title=Tolerance to nitrous oxide analgesia in rats and mice |vauthors=Berkowitz BA, Finck AD, Hynes MD, Ngai SH |journal=Anesthesiology |volume=51 |issue=4 |pages=309–12 |year=1979 |doi=10.1097/00000542-197910000-00006 |pmid=484891|s2cid=26281498 |doi-access=free }}</ref> Administration of [[antibodies]] that bind and block the activity of some endogenous opioids (not [[Beta-Endorphin|β-endorphin]]) also block the antinociceptive effects of {{chem|N|2|O}}.<ref name="branda">{{cite journal|title=Role of brain dynorphin in nitrous oxide antinociception in mice |vauthors=Branda EM, Ramza JT, Cahill FJ, Tseng LF, Quock RM |journal=Pharmacology Biochemistry and Behavior |volume=65 |pages=217–21 |year=2000 |doi=10.1016/S0091-3057(99)00202-6 |pmid=10672972 |issue=2|s2cid=1978597 |url=https://www.semanticscholar.org/paper/bab67d14373e7e5f03c6485e6ce47e93459eaf2a }}</ref> Drugs that inhibit the breakdown of endogenous opioids also potentiate the antinociceptive effects of {{chem|N|2|O}}.<ref name="branda" /> Several experiments have shown that opioid receptor antagonists applied directly to the brain block the antinociceptive effects of {{chem|N|2|O}}, but these drugs have no effect when injected into the [[spinal cord]].

Apart from an indirect action, nitrous oxide, like morphine <ref>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</ref> also interacts directly with the endogenous opioid system by binding at opioid receptor binding sites.<ref>(Daras, C., Cantrill, R. C., Gillman, M. A. [1983]. 3[H]-Naloxone displacement: evidence for nitrous oxide as an opioid agonist. European Journal of Pharmacology 89: 177-8.</ref><ref>Ori, C., Ford-Rice, F., London, E. D. [1989]. Effects of nitrous oxide and halothane on mu and kappa opioid receptors in guinea-pig brain. Anesthesiology 70: 541-544.)</ref>

Conversely, [[alpha-2 adrenergic receptor|α{{ssub|2}}-adrenoceptor]] antagonists block the pain-reducing effects of {{chem|N|2|O}} when given directly to the spinal cord, but not when applied directly to the brain.<ref name="guo">{{cite journal|title=Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice |vauthors=Guo TZ, Davies MF, Kingery WS, Patterson AJ, Limbird LE, Maze M |journal=Anesthesiology |volume=90 |issue=2 |pages=470–6 |year=1999 |pmid=9952154 |doi=10.1097/00000542-199902000-00022|doi-access=free }}</ref> Indeed, [[alpha-2B adrenergic receptor|α{{ssub|2B}}-adrenoceptor]] knockout mice or animals depleted in [[norepinephrine]] are nearly completely resistant to the antinociceptive effects of {{chem|N|2|O}}.<ref>{{cite journal|title=Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]{{ssub|2B}} adrenoceptors |vauthors=Sawamura S, Kingery WS, Davies MF, Agashe GS, Clark JD, Koblika BK, Hashimoto T, Maze M |journal=J. Neurosci. |volume=20 |issue=24 |pages=9242–51 |year=2000 |pmid=11125002 |pmc=6773006 |doi=10.1523/JNEUROSCI.20-24-09242.2000 }}</ref> Apparently {{chem|N|2|O}}-induced release of endogenous opioids causes disinhibition of [[brainstem]] noradrenergic neurons, which release norepinephrine into the spinal cord and inhibit pain signalling.<ref name="pmid10781114">{{cite journal|vauthors=Maze M, Fujinaga M |title=Recent advances in understanding the actions and toxicity of nitrous oxide |journal=Anaesthesia |volume=55 |issue=4 |pages=311–4 |year=2000 |pmid=10781114 |doi=10.1046/j.1365-2044.2000.01463.x|s2cid=39823627 |doi-access=free }}</ref> Exactly how {{chem|N|2|O}} causes the release of endogenous opioid peptides remains uncertain.

==Properties and reactions==
Nitrous oxide is a colourless gas with a faint, sweet odour.

Nitrous oxide supports combustion by releasing the [[Coordinate covalent bond|dipolar bonded]] oxygen radical, and can thus relight a glowing [[Splint (laboratory equipment)|splint]].

{{chem|N|2|O}} is inert at room temperature and has few reactions. At elevated temperatures, its reactivity increases. For example, nitrous oxide reacts with {{chem|link=Sodium amide|NaNH|2}} at {{convert|460|K|C}} to give {{chem|link=Sodium azide|NaN|3}}:
: <chem>2 NaNH2 + N2O -> NaN3 + NaOH + NH3</chem>

The above reaction is the route adopted by the commercial chemical industry to produce [[azide]] salts, which are used as detonators.<ref name="InorgChem">{{cite book|title=Inorganic Chemistry|url=https://archive.org/details/inorganicchemist00hous_159|url-access=limited|publisher=Pearson|year=2008|isbn=978-0-13-175553-6|edition=3rd|page=[https://archive.org/details/inorganicchemist00hous_159/page/n502 464]|chapter=Chapter 15: The group 15 elements|author1=Housecroft, Catherine E.|author2=Sharpe, Alan G.|name-list-style=amp}}</ref>

==History==
The gas was first synthesised in 1772 by English [[Natural philosophy|natural philosopher]] and chemist [[Joseph Priestley]] who called it ''dephlogisticated nitrous air'' (see [[phlogiston theory]])<ref name="Nitrous Oxide pioneers">{{cite journal|last=Keys|first=T.E.|year=1941|title=The Development of Anesthesia|journal=Anesthesiology|volume=2|issue=5|pages=552–574|bibcode=1982AmSci..70..522D|doi=10.1097/00000542-194109000-00008|s2cid=73062366|doi-access=free}}</ref> or ''inflammable nitrous air''.<ref>{{cite journal|last1=McEvoy|first1=J. G.|title=Gases, God and the balance of nature: a commentary on Priestley (1772) 'Observations on different kinds of air'|journal=Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences|date=6 March 2015|volume=373|issue=2039|page=20140229|doi=10.1098/rsta.2014.0229|pmc=4360083|pmid=25750146|bibcode=2015RSPTA.37340229M}}</ref> Priestley published his discovery in the book [[Experiments and Observations on Different Kinds of Air|''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]].<ref name="Joseph Priestley">{{cite web |year=1776|title=Experiments and Observations on Different Kinds of Air |website=Erowid |url=http://www.erowid.org/chemicals/nitrous/nitrous_journal1.shtml |author=Priestley J}}</ref>

===Early use===
[[File:Laughing_gas_Rumford_Davy.jpg|upright=1.4|thumb|"Living Made Easy": A satirical print from 1830 depicting [[Humphry Davy]] administering a dose of laughing gas to a woman|left]]
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".<ref name="Drug discovery" />

[[File:Anaesthesia exhibition, 1946 Wellcome M0009908.jpg|thumb|right|Sir [[Humphry Davy]]'s ''Researches chemical and philosophical: chiefly concerning nitrous oxide'' (1800), pages 556 and 557 (right), outlining potential anaesthetic properties of nitrous oxide in relieving pain during surgery]]
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 trial]]s,{{Clarify|date=April 2011}} 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.<ref name="Drug discovery" /> 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.<ref name="Humphry Davy">{{cite book|url=https://books.google.com/books?id=jhUAAAAAQAAJ|title=Researches, chemical and philosophical –chiefly concerning nitrous oxide or dephlogisticated nitrous air, and its respiration|publisher=Printed for J. Johnson|year=1800|author=Davy H}}</ref> Davy coined the name "laughing gas" for nitrous oxide.<ref>{{cite book|last1=Hardman|first1=Jonathan G.|title=Oxford Textbook of Anaesthesia|date=2017|publisher=Oxford University Press|page=529|isbn=978-0-19-964204-5}}</ref>

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 [[Anesthesia|anaesthesia]]. The use of nitrous oxide as a [[Recreational drug use|recreational drug]] at "laughing gas parties", primarily arranged for the [[Social class in the United Kingdom#Upper class|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.<ref name="Illicit drugs">{{cite web|url=http://www.druglibrary.org/schaffer/Library/studies/cu/CU43.html|title=Consumers Union Report on Licit and Illicit Drugs, Part VI – Inhalants and Solvents and Glue-Sniffing|year=1972|author=Brecher EM|work=Consumer Reports Magazine|access-date=18 December 2013}}</ref>

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.<ref name="wp">{{cite news|url=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|title=George Poe is Dead|date=3 February 1914|newspaper=Washington Post|access-date=29 December 2007|archive-date=1 March 2013|archive-url=https://web.archive.org/web/20130301050848/http://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}}</ref>

=== Anaesthetic use ===

{{Further|Nitrous oxide (medication)}}

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.<ref name="Discovery of Wells">{{Cite journal|year=1933|title=The Discoverer of Anæsthesia: Dr. Horace Wells of Hartford.|journal=The Yale Journal of Biology and Medicine|volume=5|issue=5|pages=421–430|pmc=2606479|pmid=21433572|last1=Erving|first1=H. W.}}</ref> 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.<ref name="Horace Wells">{{cite book|url=https://books.google.com/books?id=exNtlBi8T4EC|title=A history of the discovery, of the application of nitrous oxide gas, ether, and other vapours, to surgical operations|publisher=J. Gaylord Wells|year=1847|author=Wells H}}</ref> 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.<ref name="Discovery of anaesthesia">{{cite journal|year=2007|title=The discovery of modern anaesthesia-contributions of Davy, Clarke, Long, Wells and Morton|url=http://www.ijaweb.org/text.asp?2007/51/6/472/61183|journal=Indian J Anaesth|volume=51|issue=6|pages=472–8|vauthors=Desai SP, Desai MS, Pandav CS}}</ref> 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, Connecticut|New Haven]] and [[New York City]].<ref name="Drug discovery" /> Over the following three years, Colton and his associates successfully administered nitrous oxide to more than 25,000 patients.<ref name="use in dentistry" /> Today, nitrous oxide is used in dentistry as an anxiolytic, as an adjunct to [[Local anesthetic|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.<ref name="Drug discovery" /> 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.<ref name="use in dentistry" /> 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 [[Quackery|quacksalvers]], who touted it as a cure for [[tuberculosis|consumption]], [[Mycobacterial cervical lymphadenitis|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.<ref name="alleged">{{cite news|url=https://www.newspapers.com/clip/3461701/alleged_forgery/|title=Alleged Forgery|date=1877-09-28|page=8|author=<!--Staff writers; no byline.-->|newspaper=[[The Inter Ocean]]|access-date=2015-10-26}}</ref><ref name="man">{{cite news|url=https://www.newspapers.com/clip/3461943/dr_blood_and_the_sawtelles/|title=A Man of Ominous Name|date=1890-02-19|author=<!--Staff writers; no byline.-->|newspaper=[[The Inter Ocean]]|access-date=2015-10-26}}</ref>

==Production==
Reviewing various methods of producing nitrous oxide is published.<ref name=CatalysisToday2005>{{cite journal |last1=Parmon |first1=V. N. |last2=Panov |first2=G. I. |last3=Uriarte |first3=A. |last4=Noskov |first4=A. S. |title=Nitrous oxide in oxidation chemistry and catalysis application and production |journal=Catalysis Today |volume=100 |issue=2005 |pages=115–131|doi=10.1016/j.cattod.2004.12.012|year=2005 }}</ref>

===Industrial methods===
[[File:Nitrous oxide production.png|thumb|Nitrous oxide production]]
Nitrous oxide is prepared on an industrial scale by carefully heating [[ammonium nitrate]]<ref name=CatalysisToday2005 /> at about 250&nbsp;°C, which decomposes into nitrous oxide and water vapour.<ref>{{cite book|last=Holleman |first=A. F. |author2=Wiberg, E. |title=Inorganic Chemistry |publisher=Academic Press |location=San Diego |year=2001 |isbn=978-0-12-352651-9}}</ref>
:<chem>NH4NO3 -> 2 H2O  + N2O</chem>

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]].<ref>{{cite web|url=http://www.sanghioverseas.com/nitrous_oxide_gas_plants/nitrous_oxide_gas_plants.htm |publisher=Sanghi Organization |title=Nitrous oxide plant |access-date=18 December 2013  |archive-url=https://web.archive.org/web/20131127131246/http://sanghioverseas.com/nitrous_oxide_gas_plants/nitrous_oxide_gas_plants.htm |archive-date=27 November 2013 }}</ref>

===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]]:<ref>[http://chemistry.tutorvista.com/inorganic-chemistry/nitrogen-family.html "Nitrogen Family"] {{Webarchive|url=https://web.archive.org/web/20141021035916/http://chemistry.tutorvista.com/inorganic-chemistry/nitrogen-family.html |date=21 October 2014 }}. chemistry.tutorvista.com</ref>
:<chem>2 NaNO3 + (NH4)2SO4 -> Na2SO4 + 2 N2O + 4 H2O </chem>

Another method involves the reaction of urea, nitric acid and sulfuric acid:<ref>[https://www.erowid.org/archive/rhodium/chemistry/nitrous.html "Preparation of Nitrous Oxide from Urea, Nitric Acid and Sulfuric Acid"].</ref>
:<chem>2 (NH2)2CO + 2 HNO3 + H2SO4 -> 2 N2O + 2 CO2 + (NH4)2SO4 + 2 H2O</chem>

Direct oxidation of ammonia with a [[manganese dioxide]]-[[Bismuth(III) oxide|bismuth oxide]] catalyst has been reported:<ref>{{cite journal|vauthors=Suwa T, Matsushima A, Suziki Y, Namina Y |title= Manufacture of Nitrous Oxide by the Catalytic Oxidation of Ammonia|journal= The Journal of the Society of Chemical Industry, Japan|volume=64|issue=11|pages= 1879–1888|year=1961|doi=10.1246/nikkashi1898.64.11_1879|doi-access=free}}</ref> cf. [[Ostwald process]].
:<chem>2 NH3 + 2 O2 -> N2O + 3 H2O</chem>

[[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:
:<chem>NH3OHCl + NaNO2 -> N2O + NaCl + 2 H2O</chem>

Treating {{chem|HNO|3}} with {{chem|SnCl|2}} and HCl also has been demonstrated:
:<chem>2 HNO3 + 8 HCl + 4 SnCl2 -> 5 H2O + 4 SnCl4 + N2O</chem>

[[Hyponitrous acid]] decomposes to N{{ssub|2}}O and water with a [[half-life]] of 16 days at 25&nbsp;°C at pH 1–3.<ref name="Wiberg&Holleman">Egon Wiberg, Arnold Frederick Holleman (2001) ''Inorganic Chemistry'', Elsevier {{ISBN|0-12-352651-5}}</ref>
:<chem>H2N2O2 -> H2O + N2O</chem>

==Atmospheric occurrence==
[[File:N2O mm.png|thumb|upright=1.2|Nitrous oxide (N<sub>2</sub>O) measured by the Advanced Global Atmospheric Gases Experiment ([http://agage.mit.edu/ AGAGE]) in the lower atmosphere ([[troposphere]]) at stations around the world. Abundances are given as pollution free monthly mean mole fractions in [[Parts-per notation|parts-per-billion]].]]
[[File:HATS Nitrous Oxide concentration.png|thumb|right|Nitrous oxide atmospheric concentration since 1978]]
[[File:HATS Nitrous Oxide growth rate.png|thumb|right|Annual growth rate of atmospheric nitrous oxide since 2000]]
[[File:Global Nitrous Oxide Budget 2020.png|thumb|Earth's nitrous oxide budget from the [[Global Carbon Project]] (2020)<ref>{{cite web |url=https://www.globalcarbonproject.org/nitrousoxidebudget/index.htm |title={{chem|N|2|O}} Budget |publisher=Global Carbon Project |access-date=2020-11-09}}</ref>]]
Nitrous oxide is a [[Atmospheric chemistry#Atmospheric composition|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&nbsp;[[Parts-per notation|ppb]] in 2017.<ref name="agage">{{cite web |url=https://agage2.eas.gatech.edu/data_archive/data_figures/monthly/pdf/N2O_mm.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://agage2.eas.gatech.edu/data_archive/data_figures/monthly/pdf/N2O_mm.pdf |archive-date=2022-10-09 |url-status=live |title=Nitrous Oxide (N2O) Mole Fraction |publisher=Massachusetts Institute of Technology |access-date=2021-02-15}}</ref> The growth rate of about 1&nbsp;ppb per year has also accelerated during recent decades.<ref name="noaaesrl">{{cite web |url=https://www.esrl.noaa.gov/gmd/ccgg/trends_n2o/ |title=Trends in Atmospheric Nitrous Oxide |publisher=National Oceanic and Atmospheric Administration / Earth System Research Laboratories |access-date=2021-02-15}}</ref>  Nitrous oxide's atmospheric abundance has grown more than 20% from a base level of about 270&nbsp;ppb in year 1750.<ref name="tar">{{cite book |url=https://www.ipcc.ch/report/ar3/wg1/|contribution= Chapter 6 |title=TAR Climate Change 2001: The Scientific Basis |page=358}}</ref>
Important atmospheric properties of {{chem|N|2|O}} are summarized in the following table:
{| class="wikitable"
! Property
! Value
|-
| [[Ozone depletion potential]] (ODP)
| 0.17<ref name=Ravishankara>{{Citation|url=https://www.sciencemag.org/content/suppl/2009/08/27/1176985.DC1/Ravishankara.SOM.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://www.sciencemag.org/content/suppl/2009/08/27/1176985.DC1/Ravishankara.SOM.pdf |archive-date=2022-10-09 |url-status=live|title=Supporting Online Material for - Nitrous Oxide (N<sub>2</sub>O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century|last1=Ravishankara|first1=A. R.|last2=Daniel|first2=John S.|last3=Portmann|first3=Robert W.|date=2009-08-27|journal= Science |volume=326|issue=5949|pages=123–125|doi=10.1126/science.1176985|pmid=19713491|bibcode=2009Sci...326..123R|s2cid=2100618}}</ref> ([[Trichlorofluoromethane|CCl<sub>3</sub>F]] = 1)
|-
| [[Global warming potential]] (GWP: 100-year)
| 265<ref name="ar5">{{cite book |url=https://www.ipcc.ch/report/ar5/wg1/ |contribution= Chapter 8 |title=AR5 Climate Change 2013: The Physical Science Basis |page=731}}</ref> ([[Carbon dioxide|CO<sub>2</sub>]] = 1)
|-
| [[Greenhouse gas#Atmospheric lifetime|Atmospheric lifetime]]
| 116 ± 9 years<ref name="ar6"/>
|-
|}

In 2022 the IPCC reported that: "The human perturbation of the natural nitrogen cycle through the use of synthetic fertilizers and manure, as well as nitrogen deposition resulting from land-based agriculture and fossil fuel burning has been the largest driver of the increase in atmospheric N2O of 31.0 ± 0.5 ppb (10%) between 1980 and 2019."<ref name="ar6">{{Cite report |title=Chapter 5: Global Carbon and other Biogeochemical Cycles and Feedbacks |url=https://www.ipcc.ch/report/ar6/wg1/chapter/chapter-5/ |access-date=2023-05-06 |website=www.ipcc.ch |language=en}}</ref>

===Emissions by source===
17.0 (12.2 to 23.5) million tonnes total annual average nitrogen in {{chem|N|2|O}} was emitted in 2007–2016.<ref name="ar6"/> About 40% of {{chem|N|2|O}} emissions are from humans and the rest are part of the natural [[nitrogen cycle]].<ref>{{Cite web |last=US EPA |first=OAR |date=2015-12-23 |title=Overview of Greenhouse Gases |url=https://www.epa.gov/ghgemissions/overview-greenhouse-gases |access-date=2023-05-04 |website=www.epa.gov |language=en}}</ref> The {{chem|N|2|O}} emitted each year by humans has a greenhouse effect equivalent to about 3 billion tonnes of carbon dioxide: for comparison humans emitted 37 billion tonnes of actual carbon dioxide in 2019, and methane equivalent to 9 billion tonnes of carbon dioxide.<ref>{{Cite web |title={{!}} Greenhouse Gas (GHG) Emissions {{!}} Climate Watch |url=https://www.climatewatchdata.org/ghg-emissions?breakBy=gas&end_year=2019&gases=n2o&start_year=1990 |access-date=2023-05-04 |website=www.climatewatchdata.org}}</ref> 

Most of the {{chem|N|2|O}} emitted into the atmosphere, from natural and anthropogenic sources, is produced by [[microorganism]]s such as [[denitrifying bacteria]] and [[fungus|fungi]] in soils and oceans.<ref name="Sloss1992">{{cite book|last=Sloss |first=Leslie L. |title=Nitrogen Oxides Control Technology Fact Book |url=https://books.google.com/books?id=--C_JAU7W8QC&pg=PA6 |year=1992 |publisher=William Andrew |isbn=978-0-8155-1294-3 |page=6}}</ref> 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%).<ref name="inputs">U.S. Environmental Protection Agency (2010), "[https://nepis.epa.gov/Exe/ZyPDF.cgi/P100717T.PDF?Dockey=P100717T.PDF Methane and Nitrous Oxide Emissions from Natural Sources]". Report EPA 430-R-10-001.</ref> [[Wetland]]s can also be [[Greenhouse gas emissions from wetlands|emitters of nitrous oxide]].<ref name=":4">{{Cite journal |last=Bange |first=Hermann W. |date=2006 |title=Nitrous oxide and methane in European coastal waters |url=https://linkinghub.elsevier.com/retrieve/pii/S0272771406002496 |journal=Estuarine, Coastal and Shelf Science |language=en |volume=70 |issue=3 |pages=361–374 |bibcode=2006ECSS...70..361B |doi=10.1016/j.ecss.2006.05.042}}</ref><ref name=":3">{{cite journal |last1=Thompson |first1=A. J. |last2=Giannopoulos |first2=G. |last3=Pretty |first3=J. |last4=Baggs |first4=E. M. |last5=Richardson |first5=D. J. |date=2012 |title=Biological sources and sinks of nitrous oxide and strategies to mitigate emissions |journal=Philosophical Transactions of the Royal Society B |volume=367 |issue=1593 |pages=1157–1168 |doi=10.1098/rstb.2011.0415 |pmc=3306631 |pmid=22451101}}</ref> Emissions from thawing [[permafrost]] may be significant, but as of 2022 this is not certain.<ref name="ar6" />

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%).<ref name="denman">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.</ref><ref>{{Cite book |url=http://www.fao.org/docrep/010/a0701e/a0701e00.HTM |title=Livestock's long shadow: Environmental issues and options |publisher=Fao.org |author1=Steinfeld, H. |author2=Gerber, P. |author3=Wassenaar, T. |author4=Castel, V. |author5=Rosales, M. |author6=de Haan, C. |name-list-style=amp |access-date=2 February 2008 |year=2006}}</ref><ref name="epaUpdated">{{cite web|url=https://www3.epa.gov/climatechange/ghgemissions/gases/n2o.html |title=Overview of Greenhouse Gases: Nitrous Oxide |publisher=U.S. Environmental Protection Agency |access-date=31 March 2016|date=23 December 2015 |url-status=live |archive-url= https://web.archive.org/web/20160812082641/https://www.epa.gov/ghgemissions/overview-greenhouse-gases |archive-date=12 August 2016 }}</ref><ref name="epa">{{cite web |url= http://www.epa.gov/nitrousoxide/sources.html |title=Nitrous Oxide: Sources and Emissions |publisher=U.S. Environmental Protection Agency |access-date=2 February 2008 |year=2006  |archive-url= https://web.archive.org/web/20080116204312/http://www.epa.gov/nitrousoxide/sources.html |archive-date=16 January 2008}}</ref><ref>IPCC. 2013. Climate change: the physical basis (WG I, full report). p. 512.</ref> Agriculture enhances nitrous oxide production through soil cultivation, the use of nitrogen [[Fertilizer|fertilisers]] and animal waste handling.<ref>{{Cite journal|last1=Thompson|first1=R. L.|last2=Lassaletta|first2=L.|last3=Patra|first3=P. K.|last4=Wilson|first4=C. |last5=Wells|first5=K. C.|last6=Gressent|first6=A.|last7=Koffi|first7=E. N.|last8=Chipperfield|first8=M. P.|last9=Winiwarter|first9=W. |last10=Davidson|first10=E. A.|last11=Tian|first11=H.|date=2019-11-18|title=Acceleration of global N 2 O emissions seen from two decades of atmospheric inversion|journal=Nature Climate Change|language=en|volume=9|issue=12 |pages=993–998|doi=10.1038/s41558-019-0613-7|issn=1758-6798|bibcode=2019NatCC...9..993T|s2cid=208302708|url=http://pure.iiasa.ac.at/id/eprint/16173/2/N2O_paper_SI_revision2_v1.docx}}</ref> 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,<ref>{{cite journal |last1=Molodovskaya |first1=Marina |last2=Warland |first2=Jon |last3=Richards |first3=Brian K. |last4=Öberg |first4=Gunilla |last5=Steenhuis |first5=Tammo S. |title=Nitrous Oxide from Heterogeneous Agricultural Landscapes: Source Contribution Analysis by Eddy Covariance and Chambers |journal=Soil Science Society of America Journal |date=2011 |volume=75 |issue=5 |page=1829 |doi=10.2136/SSSAJ2010.0415|bibcode=2011SSASJ..75.1829M }}</ref> and the majority of a year's emissions may occur when conditions are favorable during "hot moments"<ref>{{cite journal | last1 = Molodovskaya | first1 = M. | last2 = Singurindy | first2 = O. | last3 = Richards | first3 = B. K. | last4 = Warland | first4 = J. S. | last5 = Johnson | first5 = M. | last6 = Öberg | first6 = G. | last7 = Steenhuis | first7 = T. S. | year = 2012 | title = Temporal variability of nitrous oxide from fertilized croplands: hot moment analysis | journal = Soil Science Society of America Journal | volume = 76 | issue = 5| pages = 1728–1740 | doi = 10.2136/sssaj2012.0039 | bibcode = 2012SSASJ..76.1728M | s2cid = 54795634 }}</ref><ref>{{cite journal |last1=Singurindy |first1=Olga |last2=Molodovskaya |first2=Marina |last3=Richards |first3=Brian K. |last4=Steenhuis |first4=Tammo S. |title=Nitrous oxide emission at low temperatures from manure-amended soils under corn (Zea mays L.) |journal=Agriculture, Ecosystems & Environment |date=July 2009 |volume=132 |issue=1–2 |pages=74–81 |doi=10.1016/j.agee.2009.03.001}}</ref> and/or at favorable locations known as "hotspots".<ref>{{cite journal | last1 = Mason | first1 = C.W. | last2 = Stoof | first2 = C.R. | last3 = Richards | first3 = B.K. | last4 = Das | first4 = S. | last5 = Goodale | first5 = C.L. | last6 = Steenhuis | first6 = T.S. | year = 2017 | title = Hotspots of nitrous oxide emission in fertilized and unfertilized perennial grasses on wetness-prone marginal land in New York State | journal = Soil Science Society of America Journal | volume = 81 | issue = 3| pages = 450–458 | doi = 10.2136/sssaj2016.08.0249 | bibcode = 2017SSASJ..81..450M }}</ref>

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 the nitration of cyclohexanone.<ref name="denman"/><ref>{{cite journal|title=Abatement of N{{ssub|2}}O emissions produced in the adipic acid industry|author1=Reimer R. A. |author2=Slaten C. S. |author3=Seapan M. |author4=Lower M. W. |author5=Tomlinson P. E. | journal = Environmental Progress| year = 1994| volume = 13| issue = 2| pages = 134–137| doi = 10.1002/ep.670130217}}</ref><ref>{{cite journal|title=Abatement of N{{ssub|2}}O emissions produced in the adipic acid industry|author1=Shimizu, A. |author2=Tanaka, K. |author3=Fujimori, M. |name-list-style=amp | journal = Chemosphere – Global Change Science| year = 2000| volume = 2| issue = 3–4| pages = 425–434| doi = 10.1016/S1465-9972(00)00024-6|bibcode=2000ChGCS...2..425S}}</ref>

===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]] ({{chem|NH|3}}) to [[nitrite]] ({{chem|NO|2|−}}) and to [[nitrate]] ({{chem|NO|3|−}})<!-- (Kowalchuk and Stephen, 2001)-->
* anaerobic heterotrophic denitrification, the stepwise reduction of {{chem|NO|3|−}} to {{chem|NO|2|-}}, [[nitric oxide]] (NO), {{chem|N|2|O}} and ultimately {{chem|N|2}}, where facultative anaerobe bacteria use {{chem|NO|3|−}} as an electron acceptor in the respiration of organic material in the condition of insufficient oxygen ({{chem|O|2}})<!-- (Knowles, 1982)-->
* nitrifier denitrification, which is carried out by autotrophic {{chem|NH|3}}-oxidising bacteria and the pathway whereby ammonia ({{chem|NH|3}}) is oxidised to nitrite ({{chem|NO|2|−}}), followed by the reduction of {{chem|NO|2|-}} to nitric oxide (NO), {{chem|N|2|O}} and molecular nitrogen ({{chem|N|2}})<!-- (Webster and Hopkins, 1996; Wrage et al., 2001)-->
* heterotrophic nitrification<!-- (Robertson and Kuenen, 1990)-->
* aerobic denitrification by the same heterotrophic nitrifiers<!-- (Robertson and Kuenen, 1990) -->
* fungal denitrification<!-- (Laughlin and Stevens, 2002) -->
* non-biological chemodenitrification<!-- (Chalk and Smith, 1983; Van Cleemput and Baert, 1984; Martikainen and De Boer, 1993; Daum and Schenk, 1998; Mørkved et al., 2007)-->

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. <!--(Mosier, 1994; Bouwman, 1996; Beauchamp, 1997; Yamulki et al. 1997; Dobbie and Smith, 2003; Smith et al. 2003; Dalal et al. 2003) -->

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|nitrous oxide reductase]].<ref>{{cite book|author1=Schneider, Lisa K. |author2=Wüst, Anja |author3=Pomowski, Anja |author4=Zhang, Lin |author5=Einsle, Oliver |chapter=No Laughing Matter: The Unmaking of the Greenhouse Gas Dinitrogen Monoxide by Nitrous Oxide Reductase |year=2014|title=The Metal-Driven Biogeochemistry of Gaseous Compounds in the Environment|pages =177–210| volume =14 |series=Metal Ions in Life Sciences |editor=Kroneck, Peter M. H. |editor2=Sosa Torres, Martha E. |publisher= Springer|doi=10.1007/978-94-017-9269-1_8|pmid=25416395|isbn=978-94-017-9268-4}}</ref>

==Environmental impact==
===Greenhouse effect===
[[File:Major greenhouse gas trends.png|thumb|right|Trends in the atmospheric abundance of long-lived greenhouse gases]]

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]] ({{chem|CO|2}}).<ref name="ar5" /> However, because of its low concentration (less than 1/1,000 of that of {{chem|C|O|2}}), its contribution to the [[greenhouse effect]] is less than one third that of carbon dioxide, and also less than [[water vapour]] and [[methane]].<ref name="clim">US Environmental Protection Agency, "[https://www.epa.gov/climate-indicators/climate-change-indicators-atmospheric-concentrations-greenhouse-gases Climate Change Indicators: Atmospheric Concentrations of Greenhouse Gases]" Web document, accessed on 2017-02-14</ref> On the other hand, since about 40% of the {{chem|N|2|O}} entering the atmosphere is the result of human activity,<ref name="denman" /> control of nitrous oxide is considered part of efforts to curb greenhouse gas emissions.<ref>{{cite web |url=http://www.grida.no/publications/other/ipcc%5Ftar/?src=/climate/ipcc_tar/wg1/247.htm |title=4.1.1 Sources of Greenhouse Gases |work=IPCC TAR WG1 2001 |access-date=21 September 2012  |archive-url=https://web.archive.org/web/20121029023441/http://www.grida.no/publications/other/ipcc%5Ftar/?src=%2Fclimate%2Fipcc_tar%2Fwg1%2F247.htm |archive-date=29 October 2012 }}</ref>

Most human caused nitrous oxide released into the atmosphere is from agriculture, when farmers add nitrogen-based fertilizers onto the fields, and through the breakdown of animal manure.  Reduction of emissions can be a hot topic in the [[politics of climate change]].<ref>{{Cite web |last=Mundschenk |first=Susanne |title=The Netherlands is showing how not to tackle climate change {{!}} The Spectator |url=https://www.spectator.co.uk/article/the-netherlands-is-showing-how-not-to-tackle-climate-change |access-date=2022-08-28 |website=www.spectator.co.uk |date=3 August 2022 |language=en}}</ref>

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.<ref>{{cite web|title=Overview of Greenhouse Gases: Nitrous Oxide Emissions|url=https://19january2017snapshot.epa.gov/ghgemissions/overview-greenhouse-gases_.html|publisher=United States Environmental Protection Agency|date=October 6, 2016|access-date=July 14, 2019}}</ref>

A rise in atmospheric nitrous oxide concentrations has been implicated as a possible contributor to the extremely intense global warming during the [[Cenomanian-Turonian boundary event]].<ref>{{cite journal |last1=Naafs |first1=B. David A. |last2=Monteiro |first2=Fanny M. |last3=Pearson |first3=Ann |last4=Higgins |first4=Meytal B. |last5=Pancost |first5=Richard D. |last6=Ridgwell |first6=Andy |date=10 December 2019 |title=Fundamentally different global marine nitrogen cycling in response to severe ocean deoxygenation |journal=[[Proceedings of the National Academy of Sciences of the United States of America]] |volume=116 |issue=50 |pages=24979–24984 |doi=10.1073/pnas.1905553116 |pmid=31767742 |pmc=6911173 |bibcode=2019PNAS..11624979N |doi-access=free }}</ref>

===Ozone layer depletion===
Nitrous oxide has also been implicated in [[ozone depletion|thinning the ozone layer]]. A 2009 study suggested that {{chem|N|2|O}} emission was the single most important ozone-depleting emission and it was expected to remain the largest throughout the 21st century.<ref name="sciozo">{{cite journal|doi=10.1126/science.1176985 |title=Nitrous Oxide (N{{ssub|2}}O): The Dominant Ozone-Depleting Substance Emitted in the 21st Century|year=2009|last1=Ravishankara|first1=A. R.|last2=Daniel|first2=J. S.|last3=Portmann|first3=R. W. |journal=Science |volume=326 |issue=5949 |pages=123–5|pmid=19713491 |bibcode = 2009Sci...326..123R |s2cid=2100618|doi-access=free}}</ref><ref>{{cite magazine|last=Grossman |first=Lisa |date=28 August 2009 |url=https://www.newscientist.com/article/dn17698-laughing-gas-is-biggest-threat-to-ozone-layer.html |title=Laughing gas is biggest threat to ozone layer |magazine=New Scientist}}</ref>

==Legality==
{{See also|Recreational use of nitrous oxide#Legality}}
In the United States, possession of nitrous oxide is legal under federal law and is not subject to [[Drug Enforcement Administration|DEA]] purview.<ref name="ccle">{{cite web |url=http://www.cognitiveliberty.org/dll/N20_state_laws.htm |title=US Nitrous Oxide Laws (alphabetically) Based on a search of online free legal databases. Conducted May 2002 |publisher=Center for Cognitive Liberty and Ethics |access-date=27 January 2008 |archive-url=https://web.archive.org/web/20080124114346/http://www.cognitiveliberty.org/dll/N20_state_laws.htm |archive-date=24 January 2008  }}</ref> 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 [[recreational drug use|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.{{Citation needed|date=July 2008}} For example, in the state of California, possession for recreational use is prohibited and qualifies as a misdemeanor.<ref>{{cite web|url=http://codes.lp.findlaw.com/cacode/PEN/3/1/10/s381b |title=CAL. PEN. CODE § 381b: California Code – Section 381b |publisher=Lp.findlaw.com}}</ref>

In August 2015, the [[Lambeth London Borough Council|Council]] of the [[London Borough of Lambeth]] ([[United Kingdom|UK]]) banned the use of the drug for recreational purposes, making offenders liable to an on-the-spot fine of up to £1,000.<ref>{{cite news |url=https://www.bbc.co.uk/news/uk-33955823 |title=Lambeth Council bans laughing gas as recreational drug |work=BBC News |date=17 August 2015 |access-date=17 August 2015 }}</ref>

In New Zealand, the [[New Zealand Ministry of Health|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.<ref>{{cite news |last=Anderton |first=Jim |date=26 June 2005 |url=http://www.beehive.govt.nz/release/time039s-sham-sales-laughing-gas |title=Time's up for sham sales of laughing gas |publisher=Beehive.govt.nz  |archive-url=https://web.archive.org/web/20150108015457/http://www.beehive.govt.nz/release/time039s-sham-sales-laughing-gas |archive-date=8 January 2015 }}</ref> 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<ref>{{cite web|url=http://www.ohiomedical.com/UserFiles/File/Medical+Gas+Cylinder+Data.pdf|title=Ohio Medical|website=www.ohiomedical.com|access-date=20 September 2017|archive-url=https://web.archive.org/web/20160417223630/http://www.ohiomedical.com/UserFiles/File/Medical%20Gas%20Cylinder%20Data.pdf|archive-date=17 April 2016}}</ref> is legal when the intended use of the gas is for medical anaesthesia.

In September 2023, the UK Government announced that nitrous oxide would be made illegal by the end of the year, with possession potentially carrying up to a two-year prison sentence or an unlimited fine.<ref>{{Cite news |date=2023-09-05 |title=Nitrous oxide: Laughing gas to be illegal by end of year |language=en-GB |work=BBC News |url=https://www.bbc.com/news/uk-66718165 |access-date=2023-09-05}}</ref>

==See also==
* [[DayCent]]
* [[Fink effect]]
* [[Nitrous oxide fuel blend]]
{{Portal bar | Medicine}}

==References==
{{Reflist}}

== External links ==
{{Commons category|Nitrous oxide}}

{{div col | small=yes }}
* [https://web.archive.org/web/20020827081011/http://osha.gov/SLTC/healthguidelines/nitrousoxide/recognition.html Occupational Safety and Health Guideline for Nitrous Oxide]
* [http://www.vega.org.uk/video/programme/111 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.
* [https://web.archive.org/web/20040205090004/http://www.npi.gov.au/database/substance-info/profiles/67.html National Pollutant Inventory – Oxide of nitrogen fact sheet]
* [https://www.cdc.gov/niosh/topics/nitrousoxide/ National Institute for Occupational Safety and Health – Nitrous Oxide]
* [https://www.cdc.gov/niosh/npg/npgd0465.html CDC – NIOSH Pocket Guide to Chemical Hazards – Nitrous Oxide]
* [http://www.justsayn2o.com/ Nitrous Oxide FAQ]
* [https://www.erowid.org/chemicals/nitrous/nitrous.shtml Erowid article on Nitrous Oxide]
* [https://www.sciencenews.org/view/generic/id/46776/title/Nitrous_oxide_fingered_as_monster_ozone_slayer Nitrous oxide fingered as monster ozone slayer] {{Webarchive|url=https://web.archive.org/web/20120929191310/http://www.sciencenews.org/view/generic/id/46776/title/Nitrous_oxide_fingered_as_monster_ozone_slayer |date=29 September 2012 }}, Science News
* [http://www.dentalfearcentral.org/help/sedation-dentistry/laughing-gas/ Dental Fear Central article on the use of nitrous oxide in dentistry]
* [http://asdb.info Altered States Database]
{{div col end}}

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