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{{Short description|Pungent chemical compound in chili peppers}}
{{Merge from|Sinus Buster|discuss=Talk:Capsaicin#Sinus Buster Merge Proposal|date=April 2011}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Use dmy dates|date=February 2023}}
{{chembox {{chembox
| Watchedfields = changed
| verifiedrevid = 442196745
| verifiedrevid = 443496864
| ImageFile1 = kapsaicyna.svg
| ImageFile1 = Capsaicin.svg
| ImageSize1 = 250px
| ImageFile2 = Capsaicin-3D-vdW.png | ImageFile2 = Capsaicin-3D-vdW.png
| PIN = (6''E'')-''N''--8-methylnon-6-enamide
| ImageSize2 = 250px
| OtherNames = (''E'')-''N''-(4-Hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide<br />8-Methyl-''N''-vanillyl-''trans''-6-nonenamide<br />''trans''-8-Methyl-''N''-vanillylnon-6-enamide<br />(''E'')-Capsaicin<br />Capsicine<br />Capsicin<br />CPS<br />Drug
| IUPACName = 8-Methyl-''N''-vanillyl-''trans''-6-nonenamide
| pronounce = {{IPAc-en|k|ae|p|ˈ|s|eI|s|I|n}} or {{IPAc-en|k|ae|p|ˈ|s|eI|ə|s|I|n}}
| OtherNames = (''E'')-N-(4-Hydroxy-3-methoxybenzyl)<br>-8-methylnon-6-enamide,<br> trans-8-Methyl-N-vanillylnon<br>-6-enamide, (''E'')-Capsaicin,<br> CPS, C
| Section1 = {{Chembox Identifiers | Section1 = {{Chembox Identifiers
|IUPHAR_ligand = 2486
| UNII_Ref = {{fdacite|correct|FDA}}
|InChI = 1/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
| UNII = S07O44R1ZM
|InChIKey = YKPUWZUDDOIDPM-SOFGYWHQBQ
| InChI = 1/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
|ChEMBL_Ref = {{ebicite|correct|EBI}}
| InChIKey = YKPUWZUDDOIDPM-SOFGYWHQBQ
|ChEMBL = 294199
| ChEMBL_Ref = {{ebicite|correct|EBI}}
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| ChEMBL = 294199
|StdInChI = 1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H27NO3/c1-14(2)8-6-4-5-7-9-18(21)19-13-15-10-11-16(20)17(12-15)22-3/h6,8,10-12,14,20H,4-5,7,9,13H2,1-3H3,(H,19,21)/b8-6+
|StdInChIKey = YKPUWZUDDOIDPM-SOFGYWHQSA-N
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|CASNo_Ref = {{cascite|correct|CAS}}
| StdInChIKey = YKPUWZUDDOIDPM-SOFGYWHQSA-N
|CASNo = 404-86-4
| CASNo_Ref = {{cascite|correct|CAS}}
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| CASNo = 404-86-4
|ChemSpiderID =1265957
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|EINECS = 206-969-8
| ChemSpiderID =1265957
|PubChem = 1548943
| EINECS = 206-969-8
|ChEBI_Ref = {{ebicite|correct|EBI}}
| PubChem = 1548943
| ChEBI = 3374 |ChEBI = 3374
|Beilstein = 2816484
| SMILES = O=C(NCc1cc(OC)c(O)cc1)CCCC/C=C/C(C)C
|UNII = S07O44R1ZM
| ATCCode_prefix = M02
|UNII_Ref = {{fdacite|correct|FDA}}
| ATCCode_suffix = AB01
|DrugBank = DB06774
| KEGG_Ref = {{keggcite|correct|kegg}}
|SMILES = O=C(NCc1cc(OC)c(O)cc1)CCCC/C=C/C(C)C
| KEGG = C06866
|KEGG_Ref = {{keggcite|correct|kegg}}
}}
|KEGG = C06866
| Section2 = {{Chembox Properties
| Formula = C<sub>18</sub>H<sub>27</sub>NO<sub>3</sub>
| MolarMass = 305.41 g/mol
| Absorption maxima = 280 nm
| Appearance =
| Density =
| MeltingPt = 62–65 °C
| BoilingPt = 210–220 °C @ 0.01 Torr
| Solubility =
}}
| Section3 = {{Chembox Hazards
| ExternalMSDS = http://siri.org/msds/f2/btk/btkxk.html
| MainHazards = Toxic ('''T''')
| RPhrases = {{R24/25}}
| SPhrases = {{S26}}, {{S36/37/39}}, {{S45}}
| FlashPt =
| Autoignition =
| NFPA-H = 2
| NFPA-F = 1
| NFPA-R = 0
}}
}} }}
| Section2 = {{Chembox Properties
{{pepper
|C=18 | H=27 | N=1 | O=3
| boxwidth=250px
|LambdaMax = 280 nm
| image=Hottest-chili-rating.gif
|Appearance = Crystalline white powder<ref>{{cite web|url=http://www.chemspider.com/Chemical-Structure.1265957.html|publisher=ChemSpider, Royal Society of Chemistry, Cambridge, UK|title=Capsaicin|date=2018|access-date=9 June 2018}}</ref>
| heat= Above Peak (]: 15,000,000-16,000,000)
|Odor = Highly pungent
|VaporPressure = {{val|1.32|e=-8|u=mm Hg}} at {{val|25|u=degC}}<ref name="pubchem">{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/1548943|publisher=PubChem, US National Library of Medicine|title=Capsaicin|date=27 May 2023|access-date=1 June 2023}}</ref>
|MeltingPtC = 62 to 65
|BoilingPtC = 210 to 220
|BoilingPt_notes = 0.01{{nbsp}}Torr
|Solubility = 0.0013{{nbsp}}g/100{{thinsp}}mL
|SolubleOther = {{ubl
|Soluble in alcohol, ], ]
|Slightly soluble in ], ], ]
}}
}}
| Section3 = {{Chembox Structure
|CrystalStruct = Monoclinic
}}
| Section4 = {{Chembox Pharmacology
|ATCCode_prefix = M02
|ATCCode_suffix = AB01
|ATC_Supplemental = {{ATC|N01|BX04}}
|Licence_EU=yes
|Legal_US = Rx-only
|Legal_US_comment = <ref name="Qutenza FDA label">{{cite web | title=Qutenza- capsaicin kit | website=DailyMed | date=10 January 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ffbbcb0-ad93-4f15-bb38-5da76a71c735 | access-date=22 February 2023}}</ref><ref>{{cite web | title=Drug Approval Package: Qutenza (capsaicin) NDA #022395 | website=U.S. ] (FDA) | date=3 October 2013 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022395_qutenza_toc.cfm | access-date=22 February 2023}}</ref>
}}
| Section5 = {{Chembox Hazards
|ExternalSDS = <ref name=pubchem/>
|GHSPictograms = {{GHS05}}{{GHS06}}{{GHS07}}{{GHS08}}
|GHSSignalWord = Danger
|HPhrases = {{H-phrases|301|302|315|318}}
|PPhrases = {{P-phrases|264|270|280|301+310|301+312|302+352|305+351+338|310|321|330|332+313|362|405|501}}
|NFPA-H = 2
|NFPA-F = 1
|NFPA-R = 0
}}
}}
{{Infobox pepper <!-- The given scoville rating is for the pure chemical compound, this should not be mistaken for food. -->
| heat = Above peak<br /> (pure capsaicin is toxic)<ref name=pubchem/>
| scoville = 16,000,000<ref name="pmid2039598">{{cite journal | vauthors = Govindarajan VS, Sathyanarayana MN | title = Capsicum--production, technology, chemistry, and quality. Part V. Impact on physiology, pharmacology, nutrition, and metabolism; structure, pungency, pain, and desensitization sequences | journal = Critical Reviews in Food Science and Nutrition | volume = 29 | issue = 6 | pages = 435–474 | year = 1991 | pmid = 2039598 | doi = 10.1080/10408399109527536 }}</ref>
}} }}
]
'''Capsaicin''' ({{IPAc-en|icon|k|æ|p|ˈ|s|eɪ|.|ɨ|s|ɪ|n}}; 8-]-''N''-]-6-nonen], (CH<sub>3</sub>)<sub>2</sub>CHCH=CH(CH<sub>2</sub>)<sub>4</sub>CONHCH<sub>2</sub>C<sub>6</sub>H<sub>3</sub>-4-(OH)-3-(OCH<sub>3</sub>) ) is the active component of ]s, which are ] belonging to the ] '']''. It is an ] for ]s, including ]s, and produces a sensation of burning in any ] with which it comes into contact. Capsaicin and several related compounds are called '''capsaicinoids''' and are produced as a ] by chili peppers, probably as deterrents against certain ]s and ].<ref name="totn"> Talk of the Nation, 15 August 2008.</ref> Pure capsaicin is a ], colorless, odorless, crystalline to waxy compound.


'''Capsaicin''' ('''8-methyl-''N''-vanillyl-6-nonenamide''') ({{IPAc-en|k|ae|p|ˈ|s|eI|s|I|n}} or {{IPAc-en|k|ae|p|ˈ|s|eI|ə|s|I|n}}) is an active component of ]s, which are plants belonging to the genus '']''. It is a potent ] for ], including humans, and produces a sensation of burning in any ] with which it comes into contact. Capsaicin and several related ]s (capsaicinoids) are produced as ]s by chili peppers, likely as deterrents against certain mammals and fungi.<ref name="totn">{{cite web | url = https://www.npr.org/templates/story/story.php?storyId=93636630 | title = What Made Chili Peppers So Spicy? | work = Talk of the Nation | date = 15 August 2008 }}</ref> Pure capsaicin is a ], colorless, highly ] (i.e., spicy) ] solid.<ref name=pubchem/>
==History==
The compound<ref>History of early research on capsaicin: Harvey W. Felter and John U. Lloyd, ''King's American Dispensatory'' (Cincinnati, Ohio: Ohio Valley Co., 1898), vol. 1, page 435. Available on-line at: http://www.henriettesherbal.com/eclectic/kings/capsicum.html. See also: Andrew G. Du Mez, "A century of the United States pharmocopoeia 1820-1920. I. The galenical oleoresins" (Ph.D. dissertation, University of Wisconsin, 1917), pages 111-132. Available on-line at: http://www.archive.org/stream/centuryofuniteds00dumerich/centuryofuniteds00dumerich_djvu.txt .</ref> was first extracted (albeit in impure form) in 1816 by Christian Friedrich Bucholz (1770–1818).<ref>C. F. Bucholz (1816) "Chemische Untersuchung der trockenen reifen spanischen Pfeffers" , ''Almanach oder Taschenbuch für Scheidekünstler und Apotheker'' (Weimar) , vol. 37, pages 1-30. </ref><ref>The results of Bucholz's and Braconnot's analyses of ''Capsicum annuum'' appear in: Jonathan Pereira, ''The Elements of Materia Medica and Therapeutics'', 3rd U.S. ed. (Philadelphia, Pennsylvania: Blanchard and Lea, 1854), vol. 2, .</ref><ref>Biographical information about Christian Friedrich Bucholz is available in: Hugh J. Rose, Henry J. Rose, and Thomas Wright, ed.s, ''A New General Biographical Dictionary'' (London, England: 1857), vol. 5, . Biographical information about C. F. Bucholz is also available (in German) on-line at: http://de.wikisource.org/ADB:Bucholtz,_Christian_Friedrich .
</ref><ref>In 1817, French chemist ] (1780-1855) also extracted the active component of peppers. See: Henri Braconnot (1817) "Examen chemique du Piment, de son principe âcre, et de celui des plantes de la famille des renonculacées" (Chemical investigation of the chili pepper, of its pungent principle , and of that of plants of the family ''Ranunculus''), ''Annales de Chemie et de Physique'', vol. 6, .<br>Other early investigators who tried to isolate the active compound in chili peppers include:<br> '''(1)''' Benjamin Maurach (see: Benjamin Maurach (1816) "Pharmaceutisch-chemische Untersuchung des spanischen Pfeffers" (Pharmaceutical-chemical investigation of Spanish peppers), ''Berlinisches Jahrbuch für die Pharmacie'', vol. 17, pages 63-73. Abstracts of Maurach's paper appear in: (i) ''Repertorium für die Pharmacie'', vol. 6, (1819); (ii) ''Allgemeine Literatur-Zeitung'', vol. 4, no. 18, (Feb. 1821); (iii) "Spanischer oder indischer Pfeffer," ''System der Materia medica'' ... , vol. 6, (1821). (Also contains abstract of Bucholz's analysis of peppers.));<br> '''(2)''' Danish geologist ] (see: Hans C. Oersted (1820) "Sur la découverte de deux nouveaux alcalis végétaux" (On the discovery of two new plant alkalis), ''Journal de physique, de chemie, d'histoire naturelle et des arts'', vol. 90, .; and<br> '''(3)''' German apothecary Ernst Witting (see: Ernst Witting (1822) "Considerations sur les bases vegetales en general, sous le point de vue pharmaceutique et descriptif de deux substances, la capsicine et la nicotianine" (Thoughts on the plant bases in general from a pharmaceutical viewpoint, and description of two substances, capsicin and nicotine), ''Beiträge für die pharmaceutische und analytische Chemie'', vol. 3, pages 43ff.)</ref> He called it "capsicin," after the genus '']'' from which it was extracted. John Clough Thresh (1850–1932), who had isolated capsaicin in almost pure form,<ref>In a series of articles, J. C. Thresh isolated capsaicin: '''(1)''' J. C. Thresh, "Isolation of capsaicin," ''The Pharmaceutical Journal and Transactions'', 3rd series, vol. 6, pages 941-947 (1876); '''(2)''' J. C. Thresh, "Capsaicin, the active principle in Capsicum fruits," ''The Pharmaceutical Journal and Transactions'', 3rd series, vol. 7, no. 315, pages 21 ff. (8 July 1876) , (1876).]. In ''The Pharmaceutical Journal and Transactions'', volume 7, see also pages 259ff and 473 ff and in vol. 8, see pages 187ff; '''(3)''' ''Year Book of Pharmacy…'' (1876), pages 250 and 543; '''(4)''' J. C. Thresh, "Note on Capsaicin," (1877), pages 24-25 and "Report on the active principle of Cayenne pepper," ''Year Book of Pharmacy…'' (1877), pages 485-488.</ref><ref>Obituary notice of J. C. Thresh: ''The British Medical Journal'', vol. 1, no. 3726, pages 1057-1058 (4 June 1932).</ref> gave it the name "capsaicin" in 1876.<ref>J King, H Wickes Felter, J Uri Lloyd (1905) A King's American Dispensatory. Eclectic Medical Publications (ISBN 1888483024)</ref> But it was Karl Micko who first isolated capsaicin in pure form in 1898.<ref>Karl Micko (1898) (On our knowledge of capsaicin), ''Zeitschrift für Untersuchung der Nahrungs- und Genussmittel'' (Journal for the Investigation of Necessities and Luxuries), vol. 1, pages 818-829. See also: Karl Micko (1899) (On the active component of Cayenne pepper), ''Zeitschrift für Untersuchung der Nahrungs- und Genussmittel'', vol. 2, pages 411-412.</ref> Capsaicin's empirical formula (chemical composition) was first determined by E. K. Nelson in 1919; he also partially elucidated capsaicin's chemical structure.<ref>E. K. Nelson. ''J. Am. Chem. Soc.'' '''1919''', ''41'', 1115–1121. {{|10.1021/ja02228a011}}</ref> Capsaicin was first synthesized in 1930 by E. Spath and S. F. Darling.<ref>Ernst Späth, Stephen F. Darling. Synthese des Capsaicins. ''Chem. Ber.'' '''1930''', ''63B'', 737–743.</ref> In 1961, similar substances were isolated from ]s by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.<ref>S Kosuge, Y Inagaki, H Okumura (1961). Studies on the pungent principles of red pepper. Part VIII. On the chemical constitutions of the pungent principles. Nippon Nogei Kagaku Kaishi (J. Agric. Chem. Soc.), 35, 923–927; (en) Chem. Abstr. 1964, 60, 9827g.</ref><ref>(ja) S Kosuge, Y Inagaki (1962) Studies on the pungent principles of red pepper. Part XI. Determination and contents of the two pungent principles. Nippon Nogei Kagaku Kaishi (J. Agric. Chem. Soc.), 36, pp. 251</ref>


== Natural function ==
In 1873 German pharmacologist ]<ref>Rudolf Buchheim (1873) "Über die 'scharfen' Stoffe" (On the "hot" substance), ''Archiv der Heilkunde'' (Archive of Medicine), vol. 14, pages 1ff. See also: R. Buchheim (1872) "Fructus Capsici," ''Vierteljahresschrift fur praktische Pharmazie'' (Quarterly Journal for Practical Pharmacy), vol. 4, pages 507ff.; reprinted (in English) in: ''Proceedings of the American Pharmaceutical Association'', vol. 22, pages 106ff (1873).</ref> (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes<ref>Endre Hőgyes, "Adatok a paprika (Capsicum annuum) élettani hatásához" , ''Orvos-természettudumányi társulatot Értesítője'' (1877); reprinted in: ''Orvosi Hetilap'' (1878), 10 pages. Published in German as: "Beitrage zur physiologischen Wirkung der Bestandtheile des ''Capiscum annuum'' (Spanischer Pfeffer)" , ''Archiv für Experimentelle Pathologie und Pharmakologie'', vol. 9, pages 117-130 (1878). See: http://www.springerlink.com/content/n54508568351x051/ .</ref> stated that "capsicol" (partially purified capsaicin<ref>F.A. Flückiger, ''Pharmakognosie des Pflanzenreiches'' ( Berlin, Germany: Gaertner's Verlagsbuchhandlung, 1891).</ref>) caused the burning feeling when in contact with ]s and increased secretion of ].
Capsaicin is present in large quantities in the ] (which holds the seeds), the internal membranes and, to a lesser extent, the other fleshy parts of the fruits of plants in the genus '']''. The seeds themselves do not produce any capsaicin, although the highest concentration of capsaicin can be found in the white ] of the inner wall, where the seeds are attached.<ref name="NMSU Q&A 2005">{{cite web| publisher = New Mexico State University – College of Agriculture and Home Economics |title=Chile Information – Frequently Asked Questions |year=2005 |url=http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub |access-date=17 May 2007 |archive-url = https://web.archive.org/web/20070504035555/http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub <!-- Bot retrieved archive --> |archive-date = 4 May 2007}}</ref>


The seeds of ''Capsicum'' plants are dispersed predominantly by birds. In birds, the ] channel does not respond to capsaicin or related chemicals but mammalian TRPV1 is very sensitive to it. This is advantageous to the plant, as chili pepper seeds consumed by birds pass through the digestive tract and can germinate later, whereas mammals have ] which destroy such seeds and prevent them from germinating.<!-- Tewksbury & Nabhan 2001, Nature 412 --> Thus, ] may have led to increasing capsaicin production because it makes the plant less likely to be eaten by animals that do not help it disperse.<ref name="Tewksbury Nabhan 2001">{{cite journal | vauthors = Tewksbury JJ, Nabhan GP | title = Seed dispersal. Directed deterrence by capsaicin in chilies | journal = Nature | volume = 412 | issue = 6845 | pages = 403–404 | date = July 2001 | pmid = 11473305 | doi = 10.1038/35086653 | bibcode = 2001Natur.412..403T | s2cid = 4389051 }}</ref> There is also evidence that capsaicin may have evolved as an ] agent.<ref>{{cite journal | vauthors = Tewksbury JJ, Reagan KM, Machnicki NJ, Carlo TA, Haak DC, Peñaloza AL, Levey DJ | title = Evolutionary ecology of pungency in wild chilies | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 33 | pages = 11808–11811 | date = August 2008 | pmid = 18695236 | pmc = 2575311 | doi = 10.1073/pnas.0802691105 | title-link = doi | doi-access = free | bibcode = 2008PNAS..10511808T }}</ref> The fungal pathogen '']'', which is known to infect wild chilies and thereby reduce seed viability, is deterred by capsaicin, which thus limits this form of predispersal seed mortality.
==Capsaicinoids==
Capsaicin is the main capsaicinoid in chili peppers, followed by ]. These two compounds are also about twice as potent to the taste and nerves as the minor capsaicinoids ], ], and ]. Dilute solutions of pure capsaicinoids produced different types of pungency; however, these differences were not noted using more concentrated solutions.


The ]-containing venom of a certain ] species (''])'' activates the same pathway of pain as is activated by capsaicin, an example of a shared pathway in both plant and animal anti-mammalian defense.<ref name="auto">{{cite journal |vauthors=Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D |date=November 2006 |title=Spider toxins activate the capsaicin receptor to produce inflammatory pain |journal=Nature |volume=444 |issue=7116 |pages=208–212 |bibcode=2006Natur.444..208S |doi=10.1038/nature05285 |pmid=17093448 |s2cid=4387600}}</ref>
Capsaicin is believed to be synthesized in the interlocular septa of chili peppers by addition of a branched-chain ] to ]amine; specifically, capsaicin is made from vanillylamine and 8-methyl-6-nonenoyl CoA (where CoA = ]).<ref>{{cite journal | author = Fujiwake H., Suzuki T., Oka S., Iwai K. | year = 1980 | title = Enzymatic formation of capsaicinoid from vanillylamine and iso-type fatty acids by cell-free extracts of Capsicum annuum var. annuum cv. Karayatsubusa | url = | journal = Agricultural and Biological Chemistry | volume = 44 | issue = | pages = 2907–2912 }}</ref><ref>I. Guzman, P.W. Bosland, and M.A. O'Connell, "Chapter 8: Heat, Color, and Flavor Compounds in ''Capsicum'' Fruit" in David R. Gang, ed., ''Recent Advances in Phytochemistry 41: The Biological Activity of Phytochemicals'' (New York, New York: Springer, 2011), .</ref> Biosynthesis depends on the gene ''AT3'', which resides at the ''pun1'' ], and which encodes a putative ].<ref>{{Cite journal|author=Stewart C, Kang BC, Liu K, ''et al.'' |title=The Pun1 gene for pungency in pepper encodes a putative acyltransferase |journal=Plant J. |volume=42 |issue=5 |pages=675–88 |year=2005 |month=June |pmid=15918882 |doi=10.1111/j.1365-313X.2005.02410.x |url=}}</ref>


==Uses==
Besides the six natural capsaicinoids, one synthetic member of the capsaicinoid family exists. ] (VNA, also PAVA) is used as a reference substance for determining the relative pungency of capsaicinoids.
===Food===
{{Main|Pungency}}
] dishes]]


Because of the burning sensation caused by capsaicin when it comes in contact with ], it is commonly used in food products to provide added spiciness or "heat" (piquancy), usually in the form of ] such as ] and ].<ref name="nyt">{{cite news|url=https://www.nytimes.com/2010/09/21/science/21peppers.html|title=A Perk of Our Evolution: Pleasure in Pain of Chilies|newspaper=New York Times|date=20 September 2010| vauthors = Gorman J |access-date=16 March 2015}}</ref> In high concentrations, capsaicin will also cause a burning effect on other sensitive areas, such as skin or eyes.<ref name="bio">{{cite journal | vauthors = Rollyson WD, Stover CA, Brown KC, Perry HE, Stevenson CD, McNees CA, Ball JG, Valentovic MA, Dasgupta P | title = Bioavailability of capsaicin and its implications for drug delivery | journal = Journal of Controlled Release | volume = 196 | pages = 96–105 | date = December 2014 | pmid = 25307998 | pmc = 4267963 | doi = 10.1016/j.jconrel.2014.09.027 }}</ref> The degree of heat found within a food is often measured on the ].<ref name="nyt"/>
{| class="wikitable"
|-
! Capsaicinoid name || Abbrev. || Typical<br>relative<br>amount || ]<br>heat units || Chemical structure
|-
| Capsaicin || C || 69% || 16,000,000
| ]
|-
| ] || DHC || 22% || 15,000,000
| ]
|-
| ] || NDHC || 7% || 9,100,000
| ]
|-
| ] || HDHC || 1% || 8,600,000
| ]
|-
| ] || HC || 1% || 8,600,000
| ]
|-
| ] || PAVA || ||
| ]
|}


There has long been a demand for capsaicin-spiced products like ], and ]s such as ] and Mexican ].<ref name="nyt" /> It is common for people to experience pleasurable and even ] effects from ingesting capsaicin.<ref name="nyt"/> Folklore among self-described "]s" attribute this to pain-stimulated release of ], a different mechanism from the local receptor overload that makes capsaicin effective as a topical ].<ref name="bio"/>
==Natural function==
Capsaicin is present in large quantities in the placental tissue (which holds the seeds), the internal membranes and, to a lesser extent, the other fleshy parts of the ]s of plants in the genus '']''. The seeds themselves do not produce any capsaicin, although the highest concentration of capsaicin can be found in the white pith of the inner wall, where the seeds are attached.<ref>{{cite web|author=New Mexico State University - College of Agriculture and Home Economics |title=Chile Information - Frequently Asked Questions |year=2005 |url=http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub |accessdate=May 17, 2007 |archiveurl = http://web.archive.org/web/20070504035555/http://spectre.nmsu.edu/dept/academic.html?i=1274&s=sub <!-- Bot retrieved archive --> |archivedate = May 4, 2007}}</ref>


{{anchor|Medical}}
The seeds of ''Capsicum'' plants are predominantly dispersed by ]s. Birds do not have the receptor to which capsaicin binds, so it does not function as an irritant for them. Chili pepper seeds consumed by birds pass through the digestive tract and can germinate later, but mammals have ], which destroy seeds and prevent them from germinating.<!-- Tewksbury & Nabhan 2001, Nature 412 --> Thus, natural selection may have led to increasing capsaicin production because it makes the plant less likely to be eaten by animals that do not help it reproduce.<ref>{{cite doi|10.1038/35086653}}</ref> There is also evidence that capsaicin evolved as an ] agent,<ref name="totn" /> and capsaicinoids are broadly anti-microbial.<ref>{{cite
|date=2008-08-19
|doi=10.1073/pnas.0802691105
|journal=Proceedings of the National Academy of Sciences
|volume=105 | issue=33 | pages=11808–11811
|url=http://www.pnas.org/content/105/33/11808.abstract
|title=Evolutionary ecology of pungency in wild chilies
|author=Joshua J. Tewksbury, Karen M. Reagan, Noelle J. Machnicki, Tomás A. Carlo,
David C. Haak, Alejandra Lorena Calderón Peñaloza, and Douglas J. Levey
|accessdate=2010-06-30
}}</ref>


===Research and pharmaceutical use===
In 2006, it was discovered that ] ] activates the same pathway of pain as is activated by capsaicin, the first demonstrated case of such a shared pathway in both plant and animal anti-mammal defense.<ref>{{Cite journal|author=Siemens J, Zhou S, Piskorowski R, ''et al.'' |title=Spider toxins activate the capsaicin receptor to produce inflammatory pain |journal=Nature |volume=444 |issue=7116 |pages=208–12 |year=2006 |month=November |pmid=17093448 |doi=10.1038/nature05285 |url=}}</ref>
Capsaicin is used as an ] in ] and ]es to relieve pain, typically in concentrations between 0.025% and 0.1%.<ref name="fattori">{{cite journal | vauthors = Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA | title = Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses | journal = Molecules | volume = 21 | issue = 7 | pages = 844 | date = June 2016 | pmid = 27367653 | pmc = 6273101 | doi = 10.3390/molecules21070844 | title-link = doi | doi-access = free }}</ref> It may be applied in cream form for the temporary relief of minor aches and pains of ]s and joints associated with ], backache, strains and ]s, often in compounds with other ].<ref name=fattori/>


It is also used to reduce the symptoms of peripheral ], such as ] ] caused by ].<ref name=fattori/> A capsaicin ] patch (''Qutenza'') for the management of this particular therapeutic indication (pain due to post-herpetic neuralgia) was approved in 2009, as a ] by both the U.S. ] (FDA)<ref>{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm|title=FDA Approves New Drug Treatment for Long-Term Pain Relief after Shingles Attacks|publisher=U.S. Food and Drug Administration|date=17 November 2009|access-date=5 January 2016|archive-date=23 November 2015|archive-url=https://web.archive.org/web/20151123231205/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm191003.htm|url-status=dead}}</ref><ref>{{cite web | title=Drug Approval Package: Qutenza (capsaicin) NDA #022395 | website=U.S. ] (FDA) | date=29 June 2010 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022395_qutenza_toc.cfm | access-date=19 August 2020}}
==Uses==
*{{cite web |date=13 November 2009 |title=Application Number: 22-395: Summary Review |website=FDA Center for Drug Evaluation and Research |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022395s000Sumr.pdf}}</ref> and the European Union.<ref>{{cite web | title=Qutenza EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/qutenza | access-date=19 August 2020}}</ref> A subsequent application to the FDA for Qutenza to be used as an analgesic in ] neuralgia was refused.<ref>{{cite web|url=http://www.medscape.com/viewarticle/759986|title=FDA Turns Down Capsaicin Patch for Painful Neuropathy in HIV|publisher=Medscape Medical News, WebMD| vauthors = Hitt E |date=9 March 2012|access-date=5 January 2016}}</ref> One 2017 review of clinical studies having limited quality found that high-dose topical capsaicin (8%) compared with control (0.4% capsaicin) provided moderate to substantial pain relief from post-herpetic neuralgia, ]-neuropathy, and ].<ref>{{cite journal | vauthors = Derry S, Rice AS, Cole P, Tan T, Moore RA | title = Topical capsaicin (high concentration) for chronic neuropathic pain in adults | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD007393 | date = January 2017 | pmid = 28085183 | pmc = 6464756 | doi = 10.1002/14651858.CD007393.pub4 | url = https://spiral.imperial.ac.uk:8443/bitstream/10044/1/49554/2/Derry_et_al-2017-.sup-2.pdf | access-date = 27 September 2018 | url-status = dead | archive-date = 15 February 2021 | archive-url = https://web.archive.org/web/20210215024258/https://spiral.imperial.ac.uk:8443/bitstream/10044/1/49554/2/Derry_et_al-2017-.sup-2.pdf | hdl = 10044/1/49554 }}</ref>
===Food===


Although capsaicin creams have been used to treat ] for reduction of itching,<ref name=fattori/><ref>{{cite journal | vauthors = Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M | title = Neurogenic inflammation induced by capsaicin in patients with psoriasis | journal = Acta Dermato-Venereologica | volume = 71 | issue = 1 | pages = 51–54 | year = 1991 | doi = 10.2340/00015555715154 | pmid = 1711752 | s2cid = 29307090 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ellis CN, Berberian B, Sulica VI, Dodd WA, Jarratt MT, Katz HI, Prawer S, Krueger G, Rex IH, Wolf JE | title = A double-blind evaluation of topical capsaicin in pruritic psoriasis | journal = Journal of the American Academy of Dermatology | volume = 29 | issue = 3 | pages = 438–442 | date = September 1993 | pmid = 7688774 | doi = 10.1016/0190-9622(93)70208-B }}</ref> a review of six ]s involving topical capsaicin for treatment of ] concluded there was insufficient evidence of effect.<ref>{{cite journal | vauthors = Gooding SM, Canter PH, Coelho HF, Boddy K, Ernst E | title = Systematic review of topical capsaicin in the treatment of pruritus | journal = International Journal of Dermatology | volume = 49 | issue = 8 | pages = 858–865 | date = August 2010 | pmid = 21128913 | doi = 10.1111/j.1365-4632.2010.04537.x | s2cid = 24484878 }}</ref> Oral capsaicin decreases ] levels moderately.<ref name="pmid33840333">{{cite journal | vauthors = Kelava L, Nemeth D, Hegyi P, Keringer P, Kovacs DK, Balasko M, Solymar M, Pakai E, Rumbus Z, Garami A | title = Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials | journal = Critical Reviews in Food Science and Nutrition | volume = 62 | issue = 25 | pages = 7025–7035 | date = April 2021 | pmid = 33840333 | doi = 10.1080/10408398.2021.1910138 | title-link = doi | doi-access = free }}</ref>
Because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes, it is commonly used in food products to give them added spice or "heat" (]). In high concentrations capsaicin will also cause a burning effect on other sensitive areas of skin. The degree of heat found within a food is often measured on the ].


There is insufficient clinical evidence to determine the role of ingested capsaicin on several human disorders, including obesity, ], ] and ].<ref name=fattori/>
Bathing mucous membrane surfaces that have contacted capsaicin with oil is the most effective way to attenuate the associated discomfort. Since oil and capsaicin are both hydrophobic hydrocarbons the capsaicin which has not already been absorbed into tissues will be picked up into solution and easily removed. Water is almost completely ineffective. Since capsaicin affects epithelial tissue especially in the non keratinized epithelium in the mouth, esophagus, nose, and eyes anything that is salty or contains alcohol will exacerbate the pain. Cold ] is the second most effective solution against the burning sensation (due to ]s having a ] effect on capsaicin<ref></ref>) and cold sugar solution (10%) at {{convert|20|°C|°F}} is almost as effective.<ref>Temporal effectiveness of mouth-rinsing on capsaicin mouth-burn. Christina Wu Nasrawia and Rose Marie Pangborn. http://dx.doi.org/10.1016/0031-9384(90)90067-E</ref> The burning sensation will slowly fade away in about 6–8 hours (maximum) if no actions are taken. In some cases people enjoy the pain and there is a growing demand for capsaicin spiced food and beverages.<ref>, '']'', September 20, 2010</ref> There have been several food products featuring capsaicin like hot sauce, salsa, and now beverages.


===Beverage=== ===Pepper spray and pests===
Capsaicinoids are also an active ingredient in riot control and personal defense ] agents.<ref name=pubchem/> When the spray comes in contact with skin, especially eyes or ]s, it produces pain and breathing difficulty in the affected individual.<ref name=pubchem/>
Recently beverage products are emerging with capsaicin as an active ingredient.<ref></ref><ref></ref> The first two capsaicin beverages to hit the market are ] Elixirs<ref></ref> launched in 2007 and Sweet16 launched in 2011.<ref></ref> It is common for people to experience pleasurable and even euphoriant effects from ingesting capsaicin. ] among self-described "]s" attributes this to pain-stimulated release of ], a different mechanism from the local receptor overload that makes capsaicin effective as a topical analgesic. In support of this theory, there is some evidence that the effect can be blocked by ] and other compounds that compete for receptor sites with endorphins and opiates.<ref></ref>


Capsaicin is also used to deter pests, specifically mammalian pests. Targets of capsaicin repellants include voles, deer, rabbits, squirrels, ], insects, and attacking dogs.<ref name="EPA facts capsaicin">{{cite web |title=R.E.D. Facts for Capsaicin |url=http://www.epa.gov/oppsrrd1/REDs/factsheets/4018fact.pdf |publisher=United States Environmental Protection Agency |access-date=13 November 2012 |url-status=dead |archive-url=https://web.archive.org/web/20121024014940/http://www.epa.gov/oppsrrd1/REDs/factsheets/4018fact.pdf |archive-date=24 October 2012 }}</ref> Ground or crushed dried chili pods may be used in birdseed to deter rodents,<ref>{{cite journal | vauthors = Jensen PG, Curtis PD, Dunn JA, Austic RE, Richmond ME | title = Field evaluation of capsaicin as a rodent aversion agent for poultry feed | journal = Pest Management Science | volume = 59 | issue = 9 | pages = 1007–1015 | date = September 2003 | pmid = 12974352 | doi = 10.1002/ps.705 }}</ref> taking advantage of the insensitivity of birds to capsaicin. The Elephant Pepper Development Trust claims that using chili peppers as a barrier crop can be a sustainable means for rural African farmers to deter elephants from eating their crops.<ref>{{cite web |title=Human Elephant Conflict and Chilli Pepper |url=http://www.elephantpepper.org/human-elephant-conflict-chilli.php |publisher=Elephant Pepper |access-date=31 May 2019}}</ref>
===Medical===
Capsaicin is currently used in topical ]s, as well as a high-dose ] (trade name '''Qutenza'''), to relieve the ] of peripheral ] such as post-herpetic ] caused by ].<ref>{{Cite journal|title= Which Treatment for Postherpetic Neuralgia? |publisher= PLoS Med |year=2005 |month=July |volume = 2 | issue = 7 |doi= 10.1371/journal.pmed.0020238|url= |journal= PLoS Medicine |pages= e238 }}</ref> It may be used in concentrations of between 0.025% and 0.075%. It may be used as a cream for the temporary relief of minor aches and pains of ]s and joints associated with ], simple backache, strains and ]s, often in compounds with other ].<ref></ref> The treatment typically involves the application of a topical ] until the area is numb. Then the capsaicin is applied by a ] wearing ]s and a face mask. The capsaicin remains on the skin until the patient starts to feel the "heat", at which point it is promptly removed. Capsaicin is also available in large ]s that can be applied to the back.


An article published in the ''Journal of Environmental Science and Health Part B'' in 2006 states that "Although hot chili pepper extract is commonly used as a component of household and garden insect-repellent formulas, it is not clear that the capsaicinoid elements of the extract are responsible for its repellency."<ref name="pmid17090499">{{cite journal | vauthors = Antonious GF, Meyer JE, Snyder JC | title = Toxicity and repellency of hot pepper extracts to spider mite, Tetranychus urticae Koch | journal = Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes | volume = 41 | issue = 8 | pages = 1383–1391 | year = 2006 | pmid = 17090499 | doi = 10.1080/0360123060096419 | bibcode = 2006JESHB..41.1383A | s2cid = 19121573 }}</ref>
Capsaicin creams are used to treat ] as an effective way to reduce itching and inflammation.<ref>{{Cite journal|author = Glinski W, Glinska-Ferenz M, Pierozynska-Dubowska M. |title= Neurogenic inflammation induced by capsaicin in patients with psoriasis. |publisher= Acta Derm Venereol. |year=1991 |volume = 71 | issue = 1 | pages = 51–4|pmid = 1711752|url= |journal = Acta dermato-venereologica }}</ref><ref>{{Cite journal|doi = 10.1016/0190-9622(93)70208-B |author = Arnold WP, van de Kerkhof PC. |title= Topical capsaicin in pruritic psoriasis. |publisher= J Am Acad Dermatol. |year=1993 |month = September |volume = 29 | issue = 3 | pages = 438–42|pmid = 8021363|url= |journal = Journal of the American Academy of Dermatology }}</ref>


The first pesticide product using solely capsaicin as the active ingredient was registered with the U.S. Department of Agriculture in 1962.<ref name="EPA facts capsaicin"/>
According to animal and human studies, the oral intake of capsaicin may increase the production of heat by the body for a short time. Due to the effect on the ] breakdown after a meal, cayenne may also be used to regulate ]s.<ref>{{Cite journal|doi = 10.1079/BJN2003938 |author = Lejeune MP, Kovacs EM, Westerterp-Plantenga MS. |title= Effect of capsaicin on substrate oxidation and weight maintenance after modest body-weight loss in human subjects.|publisher= Br J Nutr. |year=2003 |month = September |volume = 90 | issue = 3 | pages = 651–59|pmid = 13129472|url= |journal = The British journal of nutrition }}</ref> Further research is required to see if capsaicin would be useful to treat obesity. ], a ] released by capsaicin, has been shown to reverse diabetes in mice,<ref name="urlBreakthrough sheds light on cause of diabetes - health - 15 December 2006 - New Scientist">{{cite web | url = http://www.newscientist.com/article/dn10812-breakthrough-sheds-light-on-cause-of-diabetes.html | title = Breakthrough sheds light on cause of diabetes | author = Motluk A, Geddes L | authorlink = | coauthors = | date = 2005-12-15 | work = Health | publisher = New Scientist | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-11-01}}</ref><ref name="pmid17900987">{{cite journal | author = Tsui H, Razavi R, Chan Y, Yantha J, Dosch HM |title = 'Sensing' autoimmunity in type 1 diabetes | journal = Trends in Molecular Medicine | volume = 13 |issue = 10 | pages = 405–13 | year = 2007 | month = October | pmid = 17900987 | doi = 10.1016/j.molmed.2007.07.006 | url = }}</ref> but the effects to insulin secretion seems to be species dependent. In humans, substance P seems to decrease insulin release and cause fluctuations in blood sugar levels.<ref name="insulin1">{{cite journal | author = Brown, M and Vale, W | title = Effects of neurotensin and substance P on plasma insulin, glucagon and glucose levels | journal = Endocrinology | volume = 98 | issue = 3 | pages = 819–822 | year = 2011 | doi = 10.1210/endo-98-3-819 | url = | pmid=1261503}}</ref>


===Equestrian sports===
In 1997, a research team led by David Julius of ] showed that capsaicin selectively binds to a protein known as ] that resides on the membranes of pain and heat sensing neurons.<ref name="pmid9349813">{{Cite journal| author = Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D | title = The capsaicin receptor: a heat-activated ion channel in the pain pathway | journal = Nature | volume = 389 | issue = 6653 | pages = 816–24 | year = 1997 | month = October | pmid = 9349813 | doi = 10.1038/39807 | url = }}</ref> TRPV1 is a heat activated calcium channel, which opens between 37 and 45 ] (98.6 and 113 ], respectively). When capsaicin binds to TRPV1, it causes the channel to open below 37 °C (]), which is why capsaicin is linked to the sensation of heat. Prolonged activation of these neurons by capsaicin depletes presynaptic ], one of the body's neurotransmitters for pain and heat. Neurons that do not contain TRPV1 are unaffected.<!--This reference has nothing to do with this effect. See talk. -->
Capsaicin is a banned substance in ] because of its hypersensitizing and pain-relieving properties.<ref name="BBC 20080821" /> At the show jumping events of the ], four horses tested positive for capsaicin, which resulted in disqualification.<ref name="BBC 20080821">{{Cite news| url=http://news.bbc.co.uk/sport2/hi/olympics/equestrian/7574220.stm | publisher=] | title=Olympic horses fail drugs tests | date=21 August 2008 | access-date=1 April 2010}}</ref>


==Irritant effects==
The result appears to be that the chemical mimics a burning sensation, the ]s are overwhelmed by the influx, and are unable to report pain for an extended period of time. With chronic exposure to capsaicin, ]s are depleted of ], leading to reduction in sensation of pain and blockade of ]. If capsaicin is removed, the neurons recover.<ref>{{cite pmid|18307678}}</ref><ref>{{cite pmid|18635498}}</ref>{{Citation needed|date=April 2011}}
===Acute health effects===
Capsaicin is a strong irritant requiring proper protective goggles, respirators, and proper hazardous material-handling procedures. Capsaicin takes effect upon skin contact (irritant, sensitizer), eye contact (irritant), ingestion, and inhalation (lung irritant, lung sensitizer). The {{LD50}} in mice is 47.2&nbsp;mg/kg.<ref name="tox">{{cite web |url=http://www.sciencelab.com/xMSDS-Capsaicin_Natural-9923296 |title=Capsaicin Material Safety Data Sheet |access-date=13 July 2007 |publisher=sciencelab.com |year=2007 |format=PDF |archive-url=https://web.archive.org/web/20070929083820/http://www.sciencelab.com/xMSDS-Capsaicin_Natural-9923296 |archive-date=29 September 2007 |url-status=dead }}</ref><ref name="pmid17365137">{{cite journal | vauthors = Johnson W | title = Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin | journal = International Journal of Toxicology | volume = 26 | issue = Suppl 1 | pages = 3–106 | year = 2007 | pmid = 17365137 | doi = 10.1080/10915810601163939 | s2cid = 208154058 | doi-access = free}}</ref>


Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers.<ref>{{cite journal | vauthors = Krenzelok EP, Jacobsen TD | title = Plant exposures ... a national profile of the most common plant genera | journal = Veterinary and Human Toxicology | volume = 39 | issue = 4 | pages = 248–249 | date = August 1997 | pmid = 9251180}}</ref> They cause burning or stinging pain to the skin and, if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain, and burning diarrhea. Eye exposure produces intense tearing, pain, ], and ].<ref name="tox2">{{Cite book|title=Goldfrank's Toxicologic Emergencies | veditors = Goldfrank LR |page=1167 |publisher=McGraw-Hill |location=New York, New York|isbn=978-0-07-144310-4|date=23 March 2007 }}</ref>
Capsaicin is being explored as a possible prophylaxis for ] by researchers in Toronto, Canada. Capsaicin was injected subcutaneously in neonatal diabetes-prone NOD mice to permanently remove a prominent subset of pancreatic sensory neurons, which express the transient receptor potential vanilloid-1 (TRPV1) protein. Insulin resistance and beta cell stress of prediabetic NOD mice are prevented when TRPV1+ neurons are eliminated. In other words, mice who were genetically predisposed to Type 1 diabetes were prevented from developing Type 1 via removal of these neurons, which are thought to attract pathogenic T-cells to attacking pancreatic beta cells (i.e., the cause of Type 1 diabetes).<ref>{{Cite journal|author=Razavi R, Chan Y, Afifiyan FN, ''et al.'' |title=TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes |journal=Cell |volume=127 |issue=6 |pages=1123–35 |year=2006 |month=December |pmid=17174891 |doi=10.1016/j.cell.2006.10.038 |url=}}</ref>


===Treatment after exposure===
The ] reports studies suggesting capsaicin is able to kill ] cells by causing them to undergo ].<ref name="Mori">{{Cite journal|last=Mori |first=A |coauthors=Lehmann S, O'Kelly J et al. |title=Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells |journal=Cancer Research |volume=66 |issue=6 |pages=3222–3229 |publisher=American Association for Cancer Research |month=March |year=2006 |url=http://cancerres.aacrjournals.org/content/66/6/3222.full |pmid=16540674 |doi=10.1158/0008-5472.CAN-05-0087 |accessdate=2008-07-22}}</ref><ref>{{cite web|author=American Association for Cancer Research |title=Pepper component hot enough to trigger suicide in prostate cancer cells |year=2006 |url=http://www.eurekalert.org/pub_releases/2006-03/aafc-pch031306.php |accessdate=January 27, 2007 }}</ref> The studies were performed on tumors formed by human prostate cancer ] grown in mouse models, and showed tumors treated with capsaicin were about one-fifth the size of the untreated tumors. There have been several clinical studies conducted in Japan and China that showed natural capsaicin directly inhibits the growth of leukemic cells.<ref name="Ito">{{Cite journal|last=Ito |first=K |coauthors=Nakazato T, Yamato K et al. |title=Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress: implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species |journal=Cancer Research |volume=64 |issue=3 |pages=1071–1078 |publisher=American Association for Cancer Research |month=February |year=2004 |url=http://cancerres.aacrjournals.org/content/64/3/1071.full |pmid=14871840 |accessdate=2008-07-22 |doi=10.1158/0008-5472.CAN-03-1670}}</ref>
The primary treatment is removal of the offending substance. Plain water is ineffective at removing capsaicin.<ref name="tox" /> Capsaicin is soluble in alcohol, which can be used to clean contaminated items.<ref name="tox" />


When capsaicin is ingested, cold milk may be an effective way to relieve the burning sensation due to ]s in milk, and the water of milk acts as a ], allowing the capsaicin to form an ] with it.<ref>{{Cite web | vauthors = Senese F | date = 23 February 2018 |url= https://antoine.frostburg.edu/chem/senese/101/features/capsaicin.shtml| work = General Chemistry Online | title = Fire and Spice| publisher = Department of Chemistry, Frostburg State University }}</ref>
Another study carried out at the ] suggests capsaicin is able to trigger ] in human ] cells as well.<ref>{{cite news|author=BBC News |title=How spicy foods can kill cancers |url=http://news.bbc.co.uk/2/hi/health/6244715.stm |accessdate=January 9, 2007 | date=2007-01-09}}</ref>


===Weight loss and regain===
Capsaicin is also the key ingredient in the experimental drug ], which is in Phase 2 trials as a long-acting analgesic to treat post-surgical and osteoarthritis pain for weeks to months after a single injection to the site of pain.<ref>{{cite web|url=http://www.mail.com/Article.aspx?articlepath=APNews%5CTop%20Headlines%5C20071030%5CHealthBeat_Peppers___Pain_20071030.xml&cat=topheadlines&subcat=&pageid=1 |title=Doctors Test Hot Sauce For Pain Relief |accessdate=2007-10-30}}{{dead link|date=June 2011}}</ref> More over, it reduces pain resulted ]<ref>{{Cite journal|author = Liana Fraenkel; Sidney T. Bogardus Jr; John Concato; Dick R. Wittink |title= Treatment Options in Knee Osteoarthritis: The Patient's Perspective |publisher= Arch Intern Med, |year=2004 |month=June |volume = 164 | pages = 1299–1304 |doi= |url= http://archinte.ama-assn.org/cgi/reprint/164/12/1299?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Capsaicin+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT |issue=12}}</ref> as well as joint or muscle pain from ] or other causes.
As of 2007, there was no evidence showing that weight loss is directly correlated with ingesting capsaicin. Well-designed ] had not been performed because the ] of capsaicin in prescribed doses under research prevented subjects from complying in the study.<ref>{{cite journal | vauthors = Diepvens K, Westerterp KR, Westerterp-Plantenga MS | title = Obesity and thermogenesis related to the consumption of caffeine, ephedrine, capsaicin, and green tea | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 292 | issue = 1 | pages = R77–R85 | date = January 2007 | pmid = 16840650 | doi = 10.1152/ajpregu.00832.2005 | s2cid = 7529851 | url = https://cris.maastrichtuniversity.nl/en/publications/d418019f-bac5-49bd-b3de-dfaf8f2c6736 }}</ref> A 2014 ] of further trials found weak evidence that consuming capsaicin before a meal might slightly reduce the amount of food consumed, and might drive food preference toward ]s.<ref>{{cite journal | vauthors = Whiting S, Derbyshire EJ, Tiwari B | title = Could capsaicinoids help to support weight management? A systematic review and meta-analysis of energy intake data | journal = Appetite | volume = 73 | pages = 183–188 | date = February 2014 | pmid = 24246368 | doi = 10.1016/j.appet.2013.11.005 | s2cid = 30252935 }}</ref>


====Proposed drug abuse deterrent==== ===Peptic ulcer ===
One 2006 review concluded that capsaicin may relieve symptoms of a ] rather than being a cause of it.<ref name="pmid16621751">{{cite journal | vauthors = Satyanarayana MN | title = Capsaicin and gastric ulcers | journal = Critical Reviews in Food Science and Nutrition | volume = 46 | issue = 4 | pages = 275–328 | date = 2006 | pmid = 16621751 | doi = 10.1080/1040-830491379236 | s2cid = 40023195 }}</ref>
Clifford Woolf, the Richard J. Kitz Professor of Anesthesia Research at ], has suggested using capsaicin to deter abuse of certain extended-release drugs such as ] and ].<ref>Cromie WJ (2006) "Using chilli peppers to burn drug abusers" {{dead link|date=June 2011}}</ref> When taken as prescribed, opioid prescription drugs such as ] or stimulant drugs such as ] release their active chemical over time, but when crushed and insufflated, taken as a suppository, chewed, or injected, the larger than normal dosage is absorbed all at once and a much stronger effect is produced that can be highly habit forming and potentially fatal due to the higher risk of overdose. Woolf has argued that adding capsaicin into the capsules would be a safe way to deter abuse. A person taking the capsule in the prescribed way (''i.e.,'' swallowing it whole) would suffer no ill effects from the additive. However, a person crushing it would expose the irritant. Anyone then chewing it, snorting it, or injecting it would be exposed to the full power of the chemical. "Imagine snorting an extract of 50 jalapeño peppers and you get the idea," Woolf said in an interview with the Harvard University Gazette. As of 2006, Woolf's proposal is still in the preliminary stages of development and the additive has not yet entered the production stage. A major downside of the idea is that drug users would likely turn to polluted street drugs rather than abusing pure pills.


===Less-than-lethal force=== ===Death===
Ingestion of high quantities of capsaicin can be deadly,<ref>{{Cite web |url=https://health.clevelandclinic.org/health-risks-of-spicy-food |title=The Health Risks of Eating Extremely Spicy Foods |website=] |date=March 12, 2023}}</ref> particularly in people with heart problems.<ref>{{Cite web |url=https://apnews.com/article/paqui-spicy-chip-challenge-death-autopsy-f81c220c549ec497bcc626dec4fc2be4 |title=Teen died from eating a spicy chip as part of social media challenge, autopsy report concludes |date=2024-05-16 |website=]}}</ref> Even healthy young people can suffer adverse health effects like ] after ingestion of capsaicin capsules.<ref>{{cite journal | vauthors = Sogut O, Kaya H, Gokdemir MT, Sezen Y | title = Acute myocardial infarction and coronary vasospasm associated with the ingestion of cayenne pepper pills in a 25-year-old male | journal = International Journal of Emergency Medicine | volume = 5 | pages = 5 | date = January 2012 | pmid = 22264348 | pmc = 3284873 | doi = 10.1186/1865-1380-5-5 | doi-access = free }}</ref>
Capsaicin is also the active ingredient in riot control and personal defense ] chemical agents. When the spray comes in contact with ], especially ]s or ]s, it is very painful, and breathing small particles of it as it disperses can cause breathing difficulty, which serves to discourage assailants. Refer to the ] for a comparison of pepper spray to other sources of capsaicin.


==Mechanism of action==
In large quantities, capsaicin can cause ].<ref name="tox" /> Symptoms of overdose include difficulty breathing, blue skin, and convulsions. The large amount needed to kill an adult human and the low concentration of capsaicin in chilies make the risk of accidental poisoning by chili consumption negligible.
The burning and painful sensations associated with capsaicin result from "defunctionalization" of ] nerve fibers by causing a topical ] in the skin.<ref name=pubchem/><ref name="drugbank">{{cite web |title=Capsaicin |url=https://go.drugbank.com/drugs/DB06774 |publisher=DrugBank |access-date=1 June 2023 |date=4 January 2023}}</ref> As a member of the ] family, capsaicin binds to a ] on nociceptor fibers called the ] (TRPV1).<ref name=drugbank/><ref>{{Cite journal|vauthors=Story GM, Crus-Orengo L | title = Feel the burn| journal = American Scientist| volume = 95| issue = 4| pages = 326–333| date = July–August 2007| doi = 10.1511/2007.66.326}}</ref><ref>{{cite journal | vauthors = Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D | title = The capsaicin receptor: a heat-activated ion channel in the pain pathway | journal = Nature | volume = 389 | issue = 6653 | pages = 816–824 | date = October 1997 | pmid = 9349813 | doi = 10.1038/39807 | s2cid = 7970319 | bibcode = 1997Natur.389..816C | doi-access = free }}</ref> TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits ]s to pass through the ] when activated.<ref name=drugbank/> The resulting ] of the neuron stimulates it to send ] to the brain.<ref name=drugbank/> By binding to TRPV1 receptors, capsaicin produces similar sensations to those of excessive heat or abrasive damage, such as warming, tingling, itching, or stinging, explaining why capsaicin is described as an irritant on the skin and eyes or by ingestion.<ref name=drugbank/>


Clarifying the mechanisms of capsaicin effects on skin nociceptors was part of awarding the 2021 ], as it led to the discovery of skin sensors for temperature and touch, and identification of the single ] causing sensitivity to capsaicin.<ref>{{Cite web|url=https://www.nobelprize.org/prizes/medicine/2021/summary/|title=The Nobel Prize in Physiology or Medicine 2021|publisher=Nobel Prize Outreach|accessdate=1 June 2023}}</ref><ref>{{Cite news|url=https://www.nytimes.com/2021/10/04/health/nobel-prize-medicine-physiology-temperature-touch.html|title=Nobel Prize Awarded to Scientists for Research About Temperature and Touch| vauthors = Santora M, Engelbrecht C |newspaper=The New York Times|date=4 October 2021}}</ref>
===Pest deterrent===
Capsaicin is also used to deter mammalian pests. A common example is the use of ground-up or crushed dried chili pods in birdseed to deter squirrels,<ref>{{cite pmid|12974352}}</ref> since birds are unaffected by capsaicin. Another example is the use of chili peppers by the ] to improve crop security for rural communities in Africa.


==History==
Although hot chili pepper extract is commonly used as a component of household and garden insect repellent formulas, it is not clear that the capsaicinoid elements of the extract are responsible for its repellency.<ref name="pmid17090499">{{Cite journal|author=Antonious GF, Meyer JE, Snyder JC |title=Toxicity and repellency of hot pepper extracts to spider mite, Tetranychus urticae Koch |journal=J Environ Sci Health B |volume=41 |issue=8 |pages=1383–91 |year=2006 |pmid=17090499 |doi=10.1080/0360123060096419 |url=}}</ref>
The compound was first extracted in impure form in 1816 by ] (1770–1818).<ref>
{{cite book| vauthors = Bucholz CF |date=1816|chapter=Chemische Untersuchung der trockenen reifen spanischen Pfeffers|trans-chapter=Chemical investigation of dry, ripe Spanish peppers|title=Almanach oder Taschenbuch für Scheidekünstler und Apotheker|location=Weimar|trans-title=Almanac or Pocketbook for Analysts and Apothecaries|volume=37|pages=1–30}}
</ref>{{efn|1=History of early research on capsaicin:
* {{cite book| vauthors = Felter HW, Lloyd JU |title=King's American Dispensatory|location=Cincinnati, Ohio|publisher=Ohio Valley Co.|date=1898|volume=1|page=435|url=http://www.henriettesherbal.com/eclectic/kings/capsicum.html}}
* {{cite thesis| vauthors = Du Mez AG |title=A century of the United States pharmocopoeia 1820–1920. I. The galenical oleoresins|type=PhD|publisher=University of Wisconsin|date=1917|pages=111–132|url=https://archive.org/stream/centuryofuniteds00dumerich/centuryofuniteds00dumerich_djvu.txt}}
* The results of Bucholz's and Braconnot's analyses of ''Capsicum annuum'' appear in: {{cite book| vauthors = Pereira J |title=The Elements of Materia Medica and Therapeutics|edition=3rd US|location=Philadelphia, Pennsylvania|publisher=Blanchard and Lea|date=1854|volume=2|url=https://books.google.com/books?id=IrXszQ77xhYC&pg=PA506|page=506}}
* Biographical information about Christian Friedrich Bucholz is available in: {{cite book| veditors = Rose HJ, Wright T |title=A New General Biographical Dictionary|location=London, England | publisher = T. Fellowes |date=1857|volume=5|url=https://books.google.com/books?id=nNRySUejNcYC&pg=PA186|page=186 | vauthors = Rose HJ }}
* Biographical information about C. F. Bucholz is also available (in German) online at: .
* Some other early investigators who also extracted the active component of peppers:
:# {{cite journal | vauthors = Maurach B | date = 1816 | title = Pharmaceutisch-chemische Untersuchung des spanischen Pfeffers | trans-title = Pharmaceutical-chemical investigation of Spanish peppers | journal = Berlinisches Jahrbuch für die Pharmacie | language = de | volume = 17 | pages = 63–73 }} Abstracts of Maurach's paper appear in: (i) ''Repertorium für die Pharmacie'', vol. 6, (1819); (ii) ''Allgemeine Literatur-Zeitung'', vol. 4, no. 18, (February 1821); (iii) "Spanischer oder indischer Pfeffer", ''System der Materia medica'' ..., vol. 6, (1821) (this reference also contains an abstract of Bucholz's analysis of peppers).
:# ], French chemist {{cite journal | vauthors = Braconnot H | date = 1817 | title = Examen chemique du Piment, de son principe âcre, et de celui des plantes de la famille des renonculacées | trans-title = Chemical investigation of the chili pepper, of its pungent principle , and of that of plants of the family ''Ranunculus'' | journal = Annales de Chimie et de Physique | language = fr | volume = 6 | pages = }}
:# ], Danish geologist {{cite journal | vauthors = Oersted HC | date = 1820 | title = Sur la découverte de deux nouveaux alcalis végétaux | trans-title = On the discovery of two new plant alkalis | journal = Journal de physique, de chemie, d'histoire naturelle et des arts | trans-journal = Journal of Physics, Chemistry, Natural History and the Arts | language = fr | volume = 90 | pages = }}
:# Ernst Witting, German apothecary {{cite journal | vauthors = Witting E | date = 1822 | title = Considerations sur les bases vegetales en general, sous le point de vue pharmaceutique et descriptif de deux substances, la capsicine et la nicotianine | trans-title = Thoughts on the plant bases in general from a pharmaceutical viewpoint, and description of two substances, capsicin and nicotine | language = fr | journal = Beiträge für die Pharmaceutische und Analytische Chemie | trans-journal = Contributions to Pharmaceutical and Analytical Chemistry | volume = 3 | pages = 43}} He called it "capsicin", after the genus '']'' from which it was extracted. John Clough Thresh (1850–1932), who had isolated capsaicin in almost pure form,<ref>In a series of articles, J. C. Thresh obtained capsaicin in almost pure form:
*{{cite journal | vauthors = Thresh JC | date = 1876 | title = Isolation of capsaicin | journal = The Pharmaceutical Journal and Transactions |series=3rd Series | volume = 6 | pages = 941–947 }}
*{{cite journal | vauthors = Thresh JC | date = 8 July 1876 | title = Capsaicin, the active principle in ''Capsicum'' fruits | journal = The Pharmaceutical Journal and Transactions |series=3rd Series | volume = 7 | issue = 315 | pages = 21| doi = <!-- --> | bibcode = <!-- --> }} [Note: This article is summarized in: {{cite journal | title = Capsaicin, the active principle in ''Capsicum'' fruits | journal = The Analyst | volume = 1 | issue = 8 | url = http://pubs.rsc.org/en/Content/ArticleLanding/1876/AN/an876010148b | pages = 148–149 | date = 1876 | doi = 10.1039/an876010148b | bibcode = 1876Ana.....1..148. }}
*''Year Book of Pharmacy…'' (1876), pages 250 and 543;
*{{cite journal | vauthors = Thresh JC | date = 1877 | title = Note on Capsaicin | url = https://archive.org/stream/yearbookofpharma1877londuoft/yearbookofpharma1877londuoft_djvu.txt | journal = Year Book of Pharmacy | pages = 24–25 }}
*{{cite journal | vauthors = Thresh JC | date = 1877 | title = Report on the active principle of Cayenne pepper | journal = Year Book of Pharmacy | pages = 485–488 }}</ref><ref>Obituary notice of J. C. Thresh: {{cite journal | vauthors = | title = John Clough Thresh, M.D., D.Sc., D.P.H | journal = British Medical Journal | volume = 1 | issue = 3726 | pages = 1057–1058 | date = June 1932 | pmid = 20776886 | pmc = 2521090 | doi = 10.1136/bmj.1.3726.1057-c }}</ref> gave it the name "capsaicin" in 1876.<ref>{{cite book | vauthors = King J, Felter HW, Lloys JU | date = 1905 | title = A King's American Dispensatory. | publisher = Eclectic Medical Publications | isbn = 1888483024}})</ref> Karl Micko isolated capsaicin in its pure form in 1898.<ref>{{cite journal | vauthors = Micko K | year = 1898 | url = https://books.google.com/books?id=8SbOAAAAMAAJ&pg=PA818|title= Zur Kenntniss des Capsaïcins |trans-title= On our knowledge of capsaicin|journal= Zeitschrift für Untersuchung der Nahrungs- und Genussmittel |volume= 1| issue = 12 |pages=818–829|language=de | doi=10.1007/bf02529190}}</ref><ref>{{cite journal| vauthors = Micko K |year=1899|url=https://books.google.com/books?id=0zwDAAAAYAAJ&pg=PA411|title= Über den wirksamen Bestandtheil des Cayennespfeffers|trans-title=On the active component of Cayenne pepper | journal = Zeitschrift für Untersuchung der Nahrungs- und Genussmittel | volume = 2 | issue = 5| pages = 411–412 |language=de | doi=10.1007/bf02529197}}</ref> Capsaicin's chemical composition was first determined in 1919 by E. K. Nelson, who also partially elucidated capsaicin's chemical structure.<ref>{{cite journal | vauthors = Nelson EK | year = 1919 | title = The constitution of capsaicin, the pungent principle of capsicum | url = https://books.google.com/books?id=Ra4UAAAAYAAJ&pg=PA1115 | journal = Journal of the American Chemical Society | volume = 41 | issue = 7| pages = 1115–1121 | doi = 10.1021/ja02228a011 | bibcode = 1919JAChS..41.1115N }}</ref> Capsaicin was first synthesized in 1930 by Ernst Spath and Stephen F. Darling.<ref>{{cite journal | vauthors = Späth E, Darling SF | year = 1930 | title = Synthese des Capsaicins | journal = Chem. Ber. | volume = 63B | issue = 3| pages = 737–743 | doi = 10.1002/cber.19300630331 }}</ref> In 1961, similar substances were isolated from ]s by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.<ref>{{cite journal | vauthors = Kosuge S, Inagaki Y, Okumura H | date = 1961 | title = Studies on the pungent principles of red pepper. Part VIII. On the chemical constitutions of the pungent principles. | journal = Nippon Nogeikagaku Kaishi | trans-journal = Journal of the Agricultural Chemical Society of Japan | language = ja | volume = 35 | pages = 923–927 | doi = 10.1271/nogeikagaku1924.35.10_923 | url = https://www.jstage.jst.go.jp/article/nskkk1962/14/9/14_9_407/_pdf | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kosuge S, Inagaki Y | date = 1962 | title = Studies on the pungent principles of red pepper. Part XI. Determination and contents of the two pungent principles. | journal = Nippon Nogeikagaku Kaishi | trans-journal = Journal of the Agricultural Chemical Society of Japan | language = ja | volume = 36 | page = 251 | doi = 10.1271/nogeikagaku1924.36.251 | doi-access = free }}</ref>
}}
In 1873 German pharmacologist ]<ref>{{cite journal | vauthors = Buchheim R | date = 1873 | title = Über die 'scharfen' Stoffe | trans-title = On the "hot" substance | journal = Archiv der Heilkunde | trans-journal = Archive of Medicine | volume = 14 }}</ref><ref>{{cite journal | vauthors = Buchheim R | date = 1872 | title = Fructus Capsici | journal = Vierteljahresschrift für praktische Pharmazie | trans-journal = Quarterly Journal for Practical Pharmacy | volume = 4 | page = 507ff | language = de }}</ref><ref>{{cite journal | vauthors = Buchheim R | title = Fructus Capsici. | journal = Proceedings of the American Pharmaceutical Association | date = 1873 | volume = 22 | pages = 106 }}</ref> (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes<ref>{{cite journal | vauthors = Hőgyes E | title = Adatok a Capsicum annuum (paprika) alkatrészeinek élettani hatásához. | trans-title = Data on the physiological effects of the pepper (''Capsicum annuum'') | language = hu | journal = Orvos-természettudumányi társulatot Értesítője | trans-journal = ulletin of the Medical Science Association | date = 1877 }}</ref><ref>{{cite journal | vauthors = Högyes A | title = Mittheilungen aus dem Institute für allgemeine Pathologie und Pharmakologie an der Universität zu Klausenburg. | journal = Archiv für experimentelle Pathologie und Pharmakologie | date = June 1878 | volume = 9 | issue = 1–2 | pages = 117–130 | doi = 10.1007/BF02125956 | s2cid = 32414315 | url = https://zenodo.org/record/2330422 }}</ref> stated that "capsicol" (partially purified capsaicin<ref>{{cite book | vauthors = Flückiger FA | title = Pharmakognosie des Pflanzenreiches | location = Berlin, Germany | publisher = Gaertner's Verlagsbuchhandlung | date = 1891 }}</ref>) caused the burning feeling when in contact with ]s and increased secretion of ].


==Capsaicinoids==
There are manufacturers that do sell a capsaicin-based gel product that is reported to be a ] (''Columba livia'') deterrent from specific roosting and loafing areas. Some of these products do have an EPA label and NSF approval.
<!-- The article "Scoville scale" links here. -->
The most commonly occurring capsaicinoids are capsaicin (69%), dihydrocapsaicin (22%), nordihydrocapsaicin (7%), homocapsaicin (1%), and homodihydrocapsaicin (1%).<ref>{{cite journal | vauthors = Bennett DJ, Kirby GW | year = 1968 |title = Constitution and biosynthesis of capsaicin| journal = J. Chem. Soc. C | pages = 442 | doi = 10.1039/j39680000442 }}</ref>


Capsaicin and dihydrocapsaicin (both 16.0 million ]) are the most ] capsaicinoids. Nordihydrocapsaicin (9.1 million SHU), homocapsaicin and homodihydrocapsaicin (both 8.6 million SHU) are about half as hot.<ref name=pmid2039598/>
===Equestrian sports===
Capsaicin is a banned substance in ] because of its hypersensitizing and pain relieving properties. At the show jumping events of the ], four horses tested positive for the substance, which resulted in disqualification.<ref>{{Cite news| url=http://news.bbc.co.uk/sport1/hi/olympics/equestrian/7574220.stm | work=BBC News | title=Olympic horses fail drugs tests | date=2008-08-21 | accessdate=2010-04-01}}</ref>


There are six natural capsaicinoids (table below). Although ] (Nonivamide, VNA, also PAVA) is produced synthetically for most applications, it does occur naturally in ''Capsicum'' species.<ref>{{cite journal | vauthors = Constant HL, Cordell GA, West DP |title = Nonivamide, a Constituent of ''Capsicum'' oleoresin |journal = Natural Products | date = April 1996 | volume = 59 | issue = 4 | pages = 425–426 | doi = 10.1021/np9600816}}</ref>
==Mechanism of action==
The burning and painful sensations associated with capsaicin result from its chemical interaction with sensory ]s. Capsaicin, as a member of the ] family, binds to a ] called the ] (VR1).<ref>
{{Cite journal
|author=Story GM, Crus-Orengo L
|title=Feel the burn
|journal=American Scientist
|volume=95
|issue=4
|pages=326–333
|year=2007
|month=July–August
|doi=10.1511/2007.66.326}}
</ref> First cloned in 1997, VR1 is an ]-type receptor. VR1, which can also be stimulated with heat and physical abrasion, permits ]s to pass through the ] and into the cell when activated. The resulting ] of the neuron stimulates it to ] the brain. By binding to the VR1 receptor, the capsaicin molecule produces the same sensation that excessive heat or abrasive damage would cause, explaining why the spiciness of capsaicin is described as a burning sensation.


{| class="wikitable sortable"
The VR1 ] has subsequently been shown to be a member of the superfamily of ] ], and as such is now referred to as {{Gene|TRPV1}}. There are a number of different ] ] that have been shown to be sensitive to different ranges of temperature and probably are responsible for our range of temperature sensation. Thus, capsaicin does not actually cause a ], or indeed any direct tissue damage at all, when chili peppers are the source of exposure. The inflammation caused by the burn or physical abrasion that the body believes it has undergone can potentially cause tissue damage in cases of extreme exposure, as is the case for many substances that trick the body into inflaming itself.
|-
! Capsaicinoid name
! {{abbr|Abbrev.|Abbreviation}}
! Typical <br />relative <br />amount
! ] <br/>heat units
! class="unsortable" | Chemical structure
|-
| Capsaicin || CPS
|| 69% || 16,000,000
| ]
|-
| ] || DHC || 22% || 16,000,000
| ]
|-
| ] || NDHC || 7% || 9,100,000
| ]
|-
| ] || HC || 1% || 8,600,000
| ]
|-
| ] || HDHC || 1% || 8,600,000
| ]
|-
| ] || PAVA || || 9,200,000
| ]
|}


==Toxicity== ==Biosynthesis==
]
===Acute health effects===
]
Capsaicin is a highly irritant material requiring proper protective goggles, respirators, and proper hazardous material handling procedures. It is hazardous in cases of skin contact (irritant, sensitizer), eye contact (irritant), ingestion, and inhalation (lung irritant, lung sensitizer). Severe over-exposure to pure capsaicin can result in death; the lethal dose ({{LD50}} in mice) is 47.2&nbsp;mg/kg.<ref name="tox">{{cite web|url=http://www.sciencelab.com/xMSDS-Capsaicin_Natural-9923296 |title=Capsaicin Material Safety Data Sheet |accessdate=2007-07-13 |publisher=sciencelab.com |year=2007 |format=PDF}}</ref> Numerous other adverse health effects can occur in mammals.<ref name="pmid17365137">{{Cite journal|author= Johnson, Wilbur|title=Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin |journal=Int. J. Toxicol. |volume=26 Suppl 1 |issue= |pages=3–106 |year=2007 |pmid=17365137 |doi=10.1080/10915810601163939 |url=}}</ref>
]
]


=== History ===
Painful exposures to capsaicin-containing peppers are among the most common plant-related exposures presented to poison centers. They cause burning or stinging pain to the skin, and if ingested in large amounts by adults or small amounts by children, can produce nausea, vomiting, abdominal pain and burning diarrhea. Eye exposure produces intense tearing, pain, ] and ].<ref name="tox2">{{Cite book|title=Goldfrank's Toxicologic Emergencies |last=Goldfrank |first=L R. (ed.) |page=1167 |publisher=McGraw-Hill |location=New York, New York|isbn=007144310X}}</ref>
The general biosynthetic pathway of capsaicin and other capsaicinoids was elucidated in the 1960s by Bennett and Kirby, and Leete and Louden. Radiolabeling studies identified phenylalanine and valine as the precursors to capsaicin.<ref>Bennett DJ, Kirby GW (1968) Constitution and biosynthesis of capsaicin. J Chem Soc C 4:442–446</ref><ref name="Leete, E. 1968"/> Enzymes of the ] pathway, phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), caffeic acid ''O''-methyltransferase (COMT) and their function in capsaicinoid biosynthesis were identified later by Fujiwake et al.,<ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Intracellular distributions of enzymes and intermediates involved in biosynthesis of capsaicin and its analogues in Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = November 1982 | volume = 46 | issue = 11 | pages = 2685–2689 | doi = 10.1080/00021369.1982.10865495 }}</ref><ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Iwai K | title = Capsaicinoid formation in the protoplast from the placenta of Capsicum fruits. | journal = Agricultural and Biological Chemistry | date = October 1982 | volume = 46 | issue = 10 | pages = 2591–2592 | doi = 10.1080/00021369.1982.10865477 }}</ref> and Sukrasno and Yeoman.<ref>{{cite journal | vauthors = Sukrasno N, Yeoman MM | year = 1993 | title = Phenylpropanoid metabolism during growth and development of ''Capsicum frutescens'' fruits | journal = Phytochemistry | volume = 32 | issue = 4| pages = 839–844 | doi=10.1016/0031-9422(93)85217-f| bibcode = 1993PChem..32..839S }}</ref> Suzuki et al. are responsible for identifying leucine as another precursor to the branched-chain ].<ref>{{cite journal | vauthors = Suzuki T, Kawada T, Iwai K | year = 1981 | title = Formation and metabolism of pungent principle of ''Capsicum'' fruits. 9. Biosynthesis of acyl moieties of capsaicin and its analogs from valine and leucine in ''Capsicum'' fruits | journal = Plant & Cell Physiology | volume = 22 | pages = 23–32 | doi = 10.1093/oxfordjournals.pcp.a076142 }}</ref> It was discovered in 1999 that pungency of chili peppers is related to higher transcription levels of key enzymes of the phenylpropanoid pathway, phenylalanine ammonia lyase, cinnamate 4-hydroxylase, caffeic acid ''O''-methyltransferase. Similar studies showed high transcription levels in the placenta of chili peppers with high pungency of genes responsible for branched-chain fatty acid pathway.<ref>{{cite journal | vauthors = Curry J, Aluru M, Mendoza M, Nevarez J, Melendrez M, O'Connell MA | year = 1999 | title = Transcripts for possible capsaicinoid biosynthetic genes are differentially accumulated in pungent and non-pungent ''Capsicum'' spp | journal = Plant Sci | volume = 148 | issue = 1 | pages = 47–57 | doi = 10.1016/s0168-9452(99)00118-1 | bibcode = 1999PlnSc.148...47C | s2cid = 86735106 }}</ref>


===Drug interactions=== ===Biosynthetic pathway===
Plants exclusively of the genus '']'' produce capsaicinoids, which are ]s.<ref>{{cite journal|vauthors=Nelson EK, Dawson LE|title=Constitution of capsaicin, the pungent principle of ''Capsicum''. III|journal=J Am Chem Soc|date=1923|volume=45|issue=9|pages=2179–2181|doi=10.1021/ja01662a023|bibcode=1923JAChS..45.2179N }}</ref> Capsaicin is believed to be synthesized in the ] ] of chili peppers and depends on the gene ''AT3'', which resides at the ''pun1'' ], and which encodes a putative ].<ref>{{cite journal | vauthors = Stewart C, Kang BC, Liu K, Mazourek M, Moore SL, Yoo EY, Kim BD, Paran I, Jahn MM | title = The Pun1 gene for pungency in pepper encodes a putative acyltransferase | journal = The Plant Journal | volume = 42 | issue = 5 | pages = 675–688 | date = June 2005 | pmid = 15918882 | doi = 10.1111/j.1365-313X.2005.02410.x | title-link = doi | doi-access = free }}</ref>
Capsaicin is indicated as interacting with a number of drugs, including the commonly prescribed high-blood pressure drug ], to induce a side-effect cough.<ref></ref>


Biosynthesis of the capsaicinoids occurs in the glands of the pepper fruit where capsaicin synthase condenses ] from the ] pathway with an acyl-CoA moiety produced by the branched-chain ].<ref name="Leete, E. 1968">{{cite journal | vauthors = Leete E, Louden MC | title = Biosynthesis of capsaicin and dihydrocapsaicin in Capsicum frutescens | journal = Journal of the American Chemical Society | volume = 90 | issue = 24 | pages = 6837–6841 | date = November 1968 | pmid = 5687710 | doi = 10.1021/ja01026a049 | bibcode = 1968JAChS..90.6837L }}</ref><ref name="Bennett, D.J. 1968">{{cite journal | vauthors = Bennett DJ, Kirby GW | year = 1968 | title = Constitution and biosynthesis of capsaicin | journal = J. Chem. Soc. C | volume = 1968 | pages = 442–446 | doi = 10.1039/j39680000442 }}</ref><ref>{{cite journal | vauthors = Fujiwake H, Suzuki T, Oka S, Iwai K | year = 1980 | title = Enzymatic formation of capsaicinoid from vanillylamine and iso-type fatty acids by cell-free extracts of ''Capsicum annuum'' var. ''annuum'' cv. Karayatsubusa | journal = Agricultural and Biological Chemistry | volume = 44 | issue = 12| pages = 2907–2912 | doi=10.1271/bbb1961.44.2907| doi-access = free | title-link=doi }}</ref><ref>{{cite book | vauthors = Guzman I, Bosland PW, O'Connell MA | chapter = Chapter 8: Heat, Color, and Flavor Compounds in ''Capsicum'' Fruit | veditors = Gang DR | title = Recent Advances in Phytochemistry 41: The Biological Activity of Phytochemicals | location = New York, New York | publisher = Springer | date = 2011 | chapter-url = https://books.google.com/books?id=--nQIHiE3QwC&pg=PA117 | pages = 117–118 | isbn = 9781441972996 }}</ref>
===Treatment after exposure===

The primary treatment is removal from exposure. Contaminated clothing should be removed and placed in airtight bags to prevent secondary exposure. Capsaicin could be washed off the skin using ], ], or other ]s, or rubbed off with oily compounds such as ], ], ] (]), ], or ].{{Citation needed|date=January 2010}} Plain water is '''ineffective''' at removing capsaicin, as are ], ], ], topical ] suspensions, and other ].{{Citation needed|date=January 2010}}
Capsaicin is the most abundant capsaicinoid found in the genus '']'', but at least ten other capsaicinoid variants exist.<ref>{{cite journal | vauthors = Kozukue N, Han JS, Kozukue E, Lee SJ, Kim JA, Lee KR, Levin CE, Friedman M | title = Analysis of eight capsaicinoids in peppers and pepper-containing foods by high-performance liquid chromatography and liquid chromatography-mass spectrometry | journal = Journal of Agricultural and Food Chemistry | volume = 53 | issue = 23 | pages = 9172–9181 | date = November 2005 | pmid = 16277419 | doi = 10.1021/jf050469j }}</ref> Phenylalanine supplies the precursor to the ] while leucine or valine provide the precursor for the branched-chain fatty acid pathway.<ref name="Leete, E. 1968"/><ref name="Bennett, D.J. 1968"/> To produce capsaicin, 8-methyl-6-nonenoyl-CoA is produced by the branched-chain fatty acid pathway and condensed with vanillylamine. Other capsaicinoids are produced by the condensation of vanillylamine with various acyl-CoA products from the branched-chain fatty acid pathway, which is capable of producing a variety of acyl-CoA moieties of different chain length and degrees of unsaturation.<ref>{{cite journal | vauthors = Thiele R, Mueller-Seitz E, Petz M | title = Chili pepper fruits: presumed precursors of fatty acids characteristic for capsaicinoids | journal = Journal of Agricultural and Food Chemistry | volume = 56 | issue = 11 | pages = 4219–4224 | date = June 2008 | pmid = 18489121 | doi = 10.1021/jf073420h | bibcode = 2008JAFC...56.4219T }}</ref> All condensation reactions between the products of the phenylpropanoid and branched-chain fatty acid pathway are mediated by capsaicin synthase to produce the final capsaicinoid product.<ref name="Leete, E. 1968"/><ref name="Bennett, D.J. 1968"/>

== Evolution ==
The ''Capsicum'' genus split from ''Solanaceae'' 19.6 million years ago, 5.4 million years after the appearance of ''Solanaceae'', and is native only to the Americas.<ref>{{Cite journal | vauthors = Yang HJ, Chung KR, Kwon DY |date=2017-09-01 |title=DNA sequence analysis tells the truth of the origin, propagation, and evolution of chili (red pepper) |journal=Journal of Ethnic Foods |language=en |volume=4 |issue=3 |pages=154–162 |doi=10.1016/j.jef.2017.08.010 |s2cid=164335348 |issn=2352-6181|doi-access=free }}</ref> Chilies only started to quickly evolve in the past 2 million years into markedly different species. This evolution can be partially attributed to a key compound found in peppers, 8-methyl-N-vanillyl-6-nonenamide, otherwise known as capsaicin. Capsaicin evolved similarly across species of chilies that produce capsaicin. Its evolution over the course of centuries is due to ] and ], across the genus '']''. Despite the fact that chilies within the ''Capsicum'' genus are found in diverse environments, the capsaicin found within them all exhibit similar properties that serve as defensive and adaptive features. Capsaicin evolved to preserve the ] of peppers against fungi infections, insects, and ] mammals.<ref>{{cite journal | vauthors = Tewksbury JJ, Reagan KM, Machnicki NJ, Carlo TA, Haak DC, Peñaloza AL, Levey DJ | title = Evolutionary ecology of pungency in wild chilies | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 33 | pages = 11808–11811 | date = August 2008 | pmid = 18695236 | pmc = 2575311 | doi = 10.1073/pnas.0802691105 | bibcode = 2008PNAS..10511808T | doi-access = free }}</ref>

=== Antifungal properties ===
Capsaicin acts as an antifungal agent in four primary ways. First, capsaicin inhibits the metabolic rate of the cells that make up the fungal biofilm.<ref>{{cite journal | vauthors = Behbehani JM, Irshad M, Shreaz S, Karched M | title = Anticandidal Activity of Capsaicin and Its Effect on Ergosterol Biosynthesis and Membrane Integrity of ''Candida albicans'' | journal = International Journal of Molecular Sciences | volume = 24 | issue = 2 | pages = 1046 | date = January 2023 | pmid = 36674560 | doi = 10.3390/ijms24021046 | pmc = 9860720 | doi-access = free }}</ref> This inhibits the area and growth rate of the fungus, since the biofilm creates an area where a fungus can grow and adhere to the chili in which capsaicin is present.<ref>{{cite journal | vauthors = Costa-Orlandi CB, Sardi JC, Pitangui NS, de Oliveira HC, Scorzoni L, Galeane MC, Medina-Alarcón KP, Melo WC, Marcelino MY, Braz JD, Fusco-Almeida AM, Mendes-Giannini MJ | title = Fungal Biofilms and Polymicrobial Diseases | journal = Journal of Fungi | volume = 3 | issue = 2 | pages = 22 | date = May 2017 | pmid = 29371540 | doi = 10.3390/jof3020022 | pmc = 5715925 | doi-access = free }}</ref> Capsaicin also inhibits fungal ]e formation, which impacts the amount of nutrients that the rest of the fungal body can receive.<ref>{{Cite web |title=How fungi are constructed |url=http://website.nbm-mnb.ca/mycologywebpages/NaturalHistoryOfFungi/Thallus.html#:~:text=Hyphae%20perform%20a%20variety%20of,the%20thallus%20(fungus%20body). |access-date=2023-05-05 |website=website.nbm-mnb.ca}}</ref> Thirdly, capsaicin disrupts the structure<ref name="Yang-2017">{{cite journal | vauthors = Yang F, Zheng J | title = Understand spiciness: mechanism of TRPV1 channel activation by capsaicin | journal = Protein & Cell | volume = 8 | issue = 3 | pages = 169–177 | date = March 2017 | pmid = 28044278 | pmc = 5326624 | doi = 10.1007/s13238-016-0353-7 }}</ref> of fungal cells and the fungal cell membranes. This has consequential negative impacts on the integrity of fungal cells and their ability to survive and proliferate. Additionally, the ] synthesis of growing fungi decreases in relation to the amount of capsaicin present in the growth area. This impacts the fungal cell membrane, and how it is able to reproduce and adapt to stressors in its environment.<ref>{{cite journal | vauthors = Jordá T, Puig S | title = Regulation of Ergosterol Biosynthesis in ''Saccharomyces cerevisiae'' | journal = Genes | volume = 11 | issue = 7 | pages = 795 | date = July 2020 | pmid = 32679672 | pmc = 7397035 | doi = 10.3390/genes11070795 | doi-access = free }}</ref>

=== Insecticidal properties ===
Capsaicin deters insects in multiple ways. The first is by deterring insects from laying their eggs on the pepper due to the effects capsaicin has on these insects.<ref>{{cite journal | vauthors = Li Y, Bai P, Wei L, Kang R, Chen L, Zhang M, Tan EK, Liu W | title = Capsaicin Functions as Drosophila Ovipositional Repellent and Causes Intestinal Dysplasia | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 9963 | date = June 2020 | pmid = 32561812 | pmc = 7305228 | doi = 10.1038/s41598-020-66900-2 | bibcode = 2020NatSR..10.9963L }}</ref> Capsaicin can cause intestinal ] upon ingestion, disrupting insect metabolism and causing damage to cell membranes within the insect.<ref>{{Cite web |title=Capsaicin Technical Fact Sheet |url=http://npic.orst.edu/factsheets/archive/Capsaicintech.html#references |access-date=2023-05-05 |website=npic.orst.edu}}</ref><ref>{{cite journal | vauthors = Claros Cuadrado JL, Pinillos EO, Tito R, Mirones CS, Gamarra Mendoza NN | title = Insecticidal Properties of Capsaicinoids and Glucosinolates Extracted from ''Capsicum chinense'' and ''Tropaeolum tuberosum'' | journal = Insects | volume = 10 | issue = 5 | pages = 132 | date = May 2019 | pmid = 31064092 | pmc = 6572632 | doi = 10.3390/insects10050132 | doi-access = free }}</ref> This in turn disrupts the standard feeding response of insects.


=== Seed dispersion and deterrents against granivorous mammals ===
Burning and pain symptoms can be effectively relieved by cooling, such as from ice, cold water, cold bottles, cold surfaces, or a flow of air from wind or a fan.{{Citation needed|date=January 2010}} In severe cases, eye burn might be treated symptomatically with topical ophthalmic ]s; mucous membrane burn with ] gel. The gel from the aloe plant has also been shown to be very effective. Capsaicin-induced ] might be treated with nebulized ]s{{Citation needed|date=January 2010}} or oral ]s{{Citation needed|date=January 2010}} or ]s.<ref name="tox2"/>
] mammals pose a risk to the propagation of chilies because their molars grind the seeds of chilies, rendering them unable to grow into new chili plants.<ref>{{cite journal | vauthors = Levey DJ, Tewksbury JJ, Cipollini ML, Carlo TA | title = A field test of the directed deterrence hypothesis in two species of wild chili | journal = Oecologia | volume = 150 | issue = 1 | pages = 61–68 | date = November 2006 | pmid = 16896774 | doi = 10.1007/s00442-006-0496-y | bibcode = 2006Oecol.150...61L | s2cid = 10892233 }}</ref><ref name="Tewksbury Nabhan 2001"/> As a result, modern chilies evolved defense mechanisms to mitigate the risk of granivorous mammals. While capsaicin is present at some level in every part of the pepper, the chemical has its highest concentration in the tissue near the seeds within chilies.<ref name="NMSU Q&A 2005" /> Birds are able to eat chilies, then disperse the seeds in their excrement, enabling propagation.<ref name="Tewksbury Nabhan 2001"/>


=== Adaptation to varying moisture levels ===
===Effects of dietary consumption===
Capsaicin is a potent defense mechanism for chilies, but it does come at a cost. Varying levels of capsaicin in chilies currently appear to be caused by an evolutionary split between surviving in dry environments, and having defense mechanisms against fungal growth, insects, and granivorous mammals.<ref>{{cite journal | vauthors = Haak DC, McGinnis LA, Levey DJ, Tewksbury JJ | title = Why are not all chilies hot? A trade-off limits pungency | journal = Proceedings. Biological Sciences | volume = 279 | issue = 1735 | pages = 2012–2017 | date = May 2012 | pmid = 22189403 | pmc = 3311884 | doi = 10.1098/rspb.2011.2091 }}</ref> Capsaicin synthesis in chilies places a strain on their water resources.<ref>{{Cite journal | vauthors = Ruiz-Lau N, Medina-Lara F, Minero-García Y, Zamudio-Moreno E, Guzmán-Antonio A, Echevarría-Machado I, Martínez-Estévez M |date=2011-03-01 |title=Water Deficit Affects the Accumulation of Capsaicinoids in Fruits of Capsicum chinense Jacq. |url=https://journals.ashs.org/hortsci/view/journals/hortsci/46/3/article-p487.xml |journal=HortScience |language=en-US |volume=46 |issue=3 |pages=487–492 |doi=10.21273/HORTSCI.46.3.487 |s2cid=86280396 |issn=0018-5345|doi-access=free }}</ref> This directly affects their fitness, as it has been observed that standard concentration of capsaicin of peppers in high moisture environments in the seeds and ]s of the peppers reduced the seeds production by 50%.<ref>{{cite journal | vauthors = Mahmood T, Rana RM, Ahmar S, Saeed S, Gulzar A, Khan MA, Wattoo FM, Wang X, Branca F, Mora-Poblete F, Mafra GS, Du X | title = Effect of Drought Stress on Capsaicin and Antioxidant Contents in Pepper Genotypes at Reproductive Stage | journal = Plants | volume = 10 | issue = 7 | pages = 1286 | date = June 2021 | pmid = 34202853 | pmc = 8309139 | doi = 10.3390/plants10071286 | doi-access = free | bibcode = 2021Plnts..10.1286M }}</ref>
Ingestion of spicy food or ground jalapeño peppers does not cause mucosal erosions or other abnormalities.<ref name="bleed1">{{Cite journal|author=Graham DY, Smith JL, Opekun AR. |title=Spicy food and the stomach. Evaluation by videoendoscopy. |journal=JAMA |year=1988 |volume=260 |issue=23 |pages=3473–5 |url= |DUPLICATE DATA: pages=3473 |doi=10.1001/jama.260.23.3473 |pmid=3210286}}</ref> Some mucosal microbleeding has been found after eating red and black peppers, but there was no significant difference between ] (used as a ]) and peppers.<ref name="effects-pepper">{{Cite journal|author=Myers BM, Smith JL, Graham DY |title=Effect of red pepper and black pepper on the stomach |journal=Am. J. Gastroenterol. |volume=82 |issue=3 |pages=211–4 |year=1987 |month=March |pmid=3103424 |doi= |url=}}</ref> The question of whether chili ingestion increases or decreases risk of stomach cancer is unresolved: a study of Mexican patients found self-reported capsaicin intake levels associated with increased stomach cancer rates (however, this is very likely attributed to ].<ref name="cancer2">{{Cite journal|author=López-Carrillo L, López-Cervantes M, Robles-Díaz G, ''et al.'' |title=Capsaicin consumption, ] positivity and gastric cancer in Mexico |journal=Int. J. Cancer |volume=106 |issue=2 |pages=277–82 |year=2003 |pmid=12800206 |doi=10.1002/ijc.11195}}</ref>) while a study of Italians suggests eating hot peppers regularly was protective against stomach cancer.<ref name="pmid2335393">{{Cite journal|doi=10.1002/ijc.2910450520 |author=Buiatti|title=A case-control study of gastric cancer and diet in Italy: II. Association with nutrients. |journal= |volume=45 |issue=5 |pages=896–901 |year=1990 |month=May |pmid=2335393 |last2=Palli |first2=D |last3=Decarli |first3=A |last4=Amadori |first4=D |last5=Avellini |first5=C |last6=Bianchi |first6=S |last7=Bonaguri |first7=C |last8=Cipriani |first8=F |last9=Cocco |first9=P}}</ref> A preliminary study using county population and mortality data showed significantly higher rates for stomach and liver cancer in counties inhabited by groups with high consumption of capsaicin-rich foods than in matched control counties.<ref name="pmid12208187">{{Cite journal|author=Archer VE, Jones DW |title=Capsaicin pepper, cancer and ethnicity |journal= |volume=59 |issue=4 |pages=450–7 |year=2002 |month=October |pmid=12208187 |doi= 10.1016/S0306-9877(02)00152-4|url=http://linkinghub.elsevier.com/retrieve/pii/S0306987702001524}}</ref> Carcinogenic, co-carcinogenic, and anticarcinogenic effects of capsaicin have been reported in animal studies.<ref name=autogenerated1>{{Cite journal|author= |title=Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin |journal=Int. J. Toxicol. |volume=26 Suppl 1 |issue= |pages=3–106 |year=2007 |pmid=17365137 |doi=10.1080/10915810601163939 |url= |last1= Johnson |first1= Wilbur}}</ref><ref>{{cite pmid|21487045}}</ref>


==See also== == See also ==<!-- Please respect alphabetical order -->
* ], the active ] flavor chemical in uncooked ], and to a lesser extent ]s (see those articles for discussion of other chemicals in them relating to pungency, and eye irritation)
* ], the only known receptor (a ] channel) for capsaicin
* ], a measurement of the spicy heat (or piquance) of a chili pepper
* ], capsaicin antagonist * ], capsaicin antagonist
* ], an ultrapotent capsaicin antagonist derived from ]
* ], the active piquant chemical in ]
* ], ], ], ]; some of the world's most capsaicin-rich fruits
* ], the active piquant chemical in ], ]es, ], and ]
* ], the active piquant flavor chemical in uncooked ] and ] (see those articles for discussion of other chemicals in them relating to pungency, and eye irritation) * ] the active flavor chemical in ]
* ]
* ], ], ] some of the world's most capsaicin-rich fruits
* ]
* ], similar in structure to capsaicin, but lack the extreme pungency, and density


==References== == References ==
{{Reflist}}
===Footnotes===
{{Reflist|2}}


===General references=== ===Notes===
{{notelist}}
* {{Cite journal|author=Dray A |title=Mechanism of action of capsaicin-like molecules on sensory neurons |journal=Life Sci. |volume=51 |issue=23 |pages=1759–65 |year=1992 |pmid=1331641 |doi= 10.1016/0024-3205(92)90045-Q|url=}}
* Garnanez RJ, McKee LH (2001) "Temporal effectiveness of sugar solutions on mouth burn by capsaicin"
* {{Cite journal|author=Henkin R |title=Cooling the burn from hot peppers |journal=JAMA |volume=266 |issue=19 |page=2766 |year=1991 |month=November |pmid=1942431 |doi= 10.1001/jama.266.19.2766b|url=}}
* {{Cite journal|author=Nasrawi CW, Pangborn RM |title=Temporal effectiveness of mouth-rinsing on capsaicin mouth-burn |journal=Physiol. Behav. |volume=47 |issue=4 |pages=617–23 |year=1990 |month=April |pmid=2385629 |doi=10.1016/0031-9384(90)90067-E |url=}}
* {{Cite journal|author=Tewksbury JJ, Nabhan GP |title=Seed dispersal. Directed deterrence by capsaicin in chilies |journal=Nature |volume=412 |issue=6845 |pages=403–4 |year=2001 |month=July |pmid=11473305 |doi=10.1038/35086653 |url=}}
* {{Cite journal|author=Kirifides ML, Kurnellas MP, Clark L, Bryant BP |title=Calcium responses of chicken trigeminal ganglion neurons to methyl anthranilate and capsaicin |journal=J. Exp. Biol. |volume=207 |issue=Pt 5 |pages=715–22 |year=2004 |month=February |pmid=14747403 |doi= 10.1242/jeb.00809|url=http://jeb.biologists.org/content/207/5/715.long}}
* Tarantula Venom, Chili Peppers Have Same "Bite," Study Finds http://news.nationalgeographic.com/news/2006/11/061108-tarantula-venom.html
* Minna M. Hamalainen, Alberto Subieta, Christopher Arpey, Timothy J. Brennan, "Differential Effect of Capsaicin Treatment on Pain-Related Behaviors After Plantar Incision," ''The Journal of Pain'', 10,6 (2009), 637-645.


== Further reading ==
==External links==
{{refbegin}}
* {{cite book | vauthors = Abdel-Salam OM | title = Capsaicin as a Therapeutic Molecule | publisher = Springer | date = 2014 | isbn = 978-3-0348-0827-9 }}
{{refend}}

== External links==
{{commons category}} {{commons category}}
{{Wiktionary}} {{Wiktionary}}
* *
*
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* {{dead link|date=June 2011}}
*
* {{dead link|date=June 2011}}
* , opinion of the Scientific Committee on Food on capsaicin.
* A ] article on .
* The Neurobiology of Disease wiki, from Connecticut College: {{dead link|date=June 2011}}.
* {{dead link|date=June 2011}}


{{Analgesics}}
{{Topical products for joint and muscular pain}}
{{Transient receptor potential channel modulators}}
{{Phytochemicals}}
{{Phenolic compounds}}
{{Histone deacetylase inhibitors}}
{{Chili peppers}}
{{Portal bar|Medicine}}
{{Authority control}}


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