Capsaicin

Structural formula
General
Surname	Capsaicin
other names	( E ) - N - (4-Hydroxy-3-methoxybenzyl) -8-methyl-6-nonenoic acid amide ( IUPAC ) ; trans -8-methyl- N- vanillyl-6-nonenoic acid amide; FEMA 3404 ; CAPSAICIN ( INCI ) ;
Molecular formula	C 18 H 27 NO 3
Brief description	colorless crystals
External identifiers / databases
EC number	206-969-8
ECHA InfoCard	100.006.337
PubChem	1548943
ChemSpider	1265957
DrugBank	DB06774
Wikidata	Q273169
Drug information
ATC code	N01 BX04 ; M02 AB01 ;
properties
Molar mass	305.41 g mol −1
Physical state	firmly
Melting point	65-66 ° C
boiling point	210-220 ° C at 1.3 Pa
solubility	practically insoluble in cold water; Easily soluble in ethanol , diethyl ether and chloroform ;
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
H and P phrases	H: 301-315-317-319-334-335
	P: 261-280-301 + 310-305 + 351 + 338-342 + 311
Toxicological data	47.2 mg kg −1 ( LD 50 , mouse , oral )
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Capsaicin (abbreviated to CPS ) is an in various peppers naturally occurring TYPES alkaloid that in mammals by acting on specific receptors a heat or sharpness stimulation the release of and connected to neuropeptides such as substance P causes. Chemically, capsaicin is a fatty acid amide , more precisely the vanillylamide of the fatty acid trans -8-methyl-6-nonenoic acid. Capsaicin is lipophilic (fat soluble).

Occurrence and representatives

Chili peppers

Capsaicin is available in different types of the genus Capsicum ( pepper ) from the family of the nightshade family Solanaceae in proportions of 0.3 to 0.5%. It is found mainly in the fruits of the Capsicum plants; These fruits, often referred to as peppers or chilli pods , are botanically berries . Capsaicin and other hot-spicy substances obtained from Capsicum are known as capsaicinoids.

Capsaicinoids

The capsaicinoids capsaicin and dihydrocapsaicin are the two main hot substances in chili peppers. According to the Scoville scale, both substances are almost twice as sharp as the capsaicinoids nordihydrocapsaicin , homocapsaicin and homodihydrocapsaicin, which are present in smaller quantities .

Capsaicinoid	abbreviation	proportion of	Scoville units
Capsaicin	C.	12-78%	16,000,000
Dihydrocapsaicin	DHC	9-66%	16,000,000
Nordihydrocapsaicin	NDHC	0-30%	9,100,000
Homocapsaicin	HC	1 %	8,600,000
Homodihydrocapsaicin	HDHC	0-22%	8,600,000
Nonivamide	PAVA	synthetic	9,200,000

Synthetic analogues

Pseudocapsaicin ( INN : Nonivamid ) is available as a synthetic substitute . Another capsaicin analog is capsazepine , which is used as a specific capsaicin antagonist .

properties

Capsaicinoids are colorless and relatively temperature stable, i. H. they can not be decomposed by boiling or freezing. Capsaicinoids dissolve in ethanol and fats , but not in water . They have an antibacterial and fungicidal effect and therefore have a preservative effect .

Capsaicinoids irritate the nerve endings of certain nociceptors , which usually detect pain stimuli when exposed to heat or chemical irritation. The similarity of the sensation of "hot" and "sharp" (engl. "Hot" or "spicy") is already on the receptor level established: Capsaicin binds to the TRP - channel TRPV1 , which is also by an increase in temperature is activated. The expression “burn” is derived from this fact. The opposite effect exists e.g. B. when exposed to low concentrations of menthol (cough drops), which seem to cool. The organism reacts to the painful, subjective irritation of capsaicinoids with increased blood flow to the tissue and the release of endorphins , which trigger a feeling of happiness - the so-called "pepper high".

In August 2010, Chinese researchers in Chongqing were able to demonstrate through studies on rats that capsaicin has a relaxing effect on the blood vessels and thus lowers blood pressure. The continuous uptake of capsaicin through the diet of the test animals resulted in an increased release of nitric oxide . Nitric oxide, in turn, is important for the blood circulation and for the relaxation of the blood vessels and thus has a blood pressure lowering effect.

Evolutionary development of capsaicin production

One possibility of the emergence of capsaicin production is an evolutionary advantage that relates to the reproduction and distribution of the genetic material, because capsaicinoids are only hot for mammals , but not for birds , whose nerve cells are structured slightly differently. This is an important selection factor for plants: By deterring mammals, their fruits are increasingly eaten by birds. Birds travel longer distances on average than mammals and can therefore spread the seeds of the plant more effectively. In addition, the birds do not grind the seeds when they eat the fruit, as mammals do when they chew. The seeds are excreted undigested and also fertilized by the bird droppings.

Another possibility was described by ecologists and evolutionary biologists Joshua J. Tewksbury and Douglas Levey. These investigated the distribution of the plants in Bolivia and in particular the concentration of the capsaicinoids present in the chilli peppers in connection with the ecological conditions in the distribution area and established a direct connection between the risk of fungal infestation and the occurrence of the beaked peckers. The chilli peppers in the areas with an increased risk of infestation by fungi, in particular of the genus Fusarium , have an increased content of fungicidal capsaicin, which ensures that the fruit will survive in these areas as well. This is a consequence of the selection, as only fruits with a high capsaicin content can survive. Other species, whose capsaicin content is not that high, only prevail in areas with a lower risk of infestation. The evolutionary biologists established a further connection with the Schnabelkerfen present in the area of distribution. The chilli fruits of the plants in an area with an increased occurrence of insects, which pierce the fruits while searching for food and thus pave the way for molds to get inside the fruits, were particularly hot. The presence of only these hot fruits with an increased capsaicin content is a direct consequence of the selection, since only plants with effective protection against mold infestation can survive here. The capsaicin not only serves to deter predators, but also to protect the fruits and their seeds against mold and the actual spread by birds.

Measurement of capsaicin spicy content

The heat of chilli peppers is measured in Scoville units (SHU = S coville H eat U nits). The scale described by Wilbur L. Scoville goes from 0 SHU (no sharpness available) to a maximum of 16 million SHU (pure capsaicin in crystalline form). Scoville measures the existing sharpness of a “substance” (in the narrower sense of the chilli pod or the extract) by neutralizing it. The proportion of the water required to dilute a substance until its sharpness is neutralized below the perceptible limit to the substance itself gives the Scoville value. Do you need z. B. 234,000 drops of water to neutralize the taste of a drop of a sauce, then the sauce has a spiciness level of 234,000 SHU. This scale is still used today, even if the capsaicin content is determined by the more precise HPLC method.

Extreme degrees of spiciness on the basis of capsaicin extraction, which i. d. As a rule, they are no longer produced purely plant-based, starting at around 100,000 SHU (e.g. with the addition of “pepper enhanced extracts”). By using pure Habanero chilis, extremely hot extracts are already possible (100,000 to 350,000 SHU). With one of the hottest chilli varieties in the world, the Indian Naga Jolokias with an empirical average value of approx. 850,000 to 1,050,000 SHU, herbal extracts and swelling products can be produced.

Producing pure, approximately crystalline capsaicin (16 million SHU; cf. Blair's 16 million reserve ) is very complex and the product is accordingly expensive. The hottest commercial extract in the world (excluding collectibles), Mad Dog 357 No.9 Plutonium , has nine million SHU.

Analytics

For reliable qualitative and quantitative determination of capsaicin, the coupling of HPLC with mass spectrometry can be used after appropriate sample preparation . This methodology can also be used for doping controls in equestrian sport.

Use and handling

The blood circulation-increasing effect is also used in ( animal ) medicine (for example with heat plasters ). Caution is advised when the bare skin comes into contact with capsaicinoids, for example when processing chili peppers. Above all, you should be careful not to rub your eyes after contact with your hands. Therefore it makes sense to wear gloves to protect the skin.

If you have eaten spicy food and the burning sensation in your mouth becomes unbearable, oil and fat emulsions such as yoghurt , milk and cheese can help . Even (high-proof) alcoholic beverages reduce the spicy sensation, as capsaicin dissolves in ethanol ; but since it is practically insoluble in cold water, water has no soothing effect. On the contrary, the sensation of pain can increase after rinsing with water because it stirs up and distributes the capsaicinoids in the oral cavity again. It was also found that a 10% sugar solution is said to be as effective as milk. Sugar or tomato juice in spicy dishes will also reduce the heat. Burning of the skin can be limited by rubbing it with alcohol. If sensitive parts of the body ( genitals , eyes ) are irritated , a little cooking oil will help.

The production of capsaicin takes place mainly in the placenta , the light orange part of the berries. Contrary to popular belief, the seeds usually do not contain capsaicin, but it can diffuse from the placenta , the concentration depends on the capsaicin content of the placenta. The statement that small chili peppers are particularly hot is only partially true. The intensity can also vary for pods of the same variety and even for pods that were harvested from the same plant at the same time.

Use as an antibiotic

In addition to the direct effects on the organism, capsaicin also has antibiotic properties. The killing of bacterial pathogens and fungi is decisive for the disinfecting effect of capsaicin. In hot and especially in tropical regions (e.g. Far East, Africa, Central America), cayenne pepper ('chili') is traditionally and habitually added to many dishes in order to prevent bacterial diseases of the digestive system.

Use as a flavoring agent

Although capsaicin is actually not a flavoring substance, as it has no taste, but only irritates the mucous membranes, the European Flavor Regulation 1334/2008 (Annex III, Part A) regulates its use. As a pure substance, capsaicin must not be added to food in any form - as an extract from chilli pods, capsaicinoids are permitted without restriction. Chilli extracts commonly used in the flavor industry have a natural capsaicinoid content of approx. 6.6% (= approx. 1,000,000 SHU).

Use in medicine

The change in pain perception after capsaicin application to the skin or mucous membrane is mediated by an attack on peripheral sensory C-fibers of the nerves and consists of two phases. An initial stimulation of the neurons with the release of substance P and other neuropeptides (with irritation and hyperesthesia) is followed by a longer refractory phase. In this, the neuron is not only insensitive to a renewed capsaicin stimulation, but also to other pain-triggering factors. This leads to a long-lasting desensitization to pain. This affects both the skin and the mucous membranes and is of medical interest.

Capsaicin is used for external applications as a cream, ointment and plaster. Indications are muscle pain and muscle tension, especially in the area of the spine. Capsicum extracts are also used for joint pain, rheumatic complaints and neuropathic pain. Unwanted side effects include local reactions such as burning sensation and reddening of the skin.

In combination with kaolin (clay), water and mustard oil , cayenne pepper (capsaicin or capsaicinoids) is used in the form of Munari packs (Italian pack) as heat therapy for pain and tension in the musculoskeletal system, individually or in combination with massage .

A meta-analysis showed that capsaicin can significantly reduce chronic pain of neuropathic and muscular causes compared to placebo. The reduction in pain by over 50% lasted eight weeks in some of the patients. There were also side effects such as local skin irritation and coughing.

A combination of capsaicin with a local anesthetic is still in the development phase . In this way, capsaicin enables access to the cell for the anesthetic without affecting other sensations.

Use as an irritant

The chilli extract Oleoresin capsicum (OC) is also used in pepper sprays, whereby the irritant is used as a “weapon” in self-defense against humans and animals. In North America, for example, sprays containing capsaicinoid are recommended as a defense against attacks by brown bears that are common there.

In Germany, pepper spray is a weapon within the meaning of the Weapons Act . The spray duration and range must be limited. Animal repellent sprays, on the other hand, are not subject to the Weapons Act, so no restrictions such as spray duration and range have to be observed. Animal repellent sprays can be purchased freely.

The medicinal mechanism of action of oleoresin capsicum is based on the stimulation of chemo- nociceptors of afferent nerves. The release of substance P leads to membrane depolarization due to the influx of sodium and calcium ions.

Possible interactions between capsaicin and drugs

Recent research by John E. Mendelson at the California Pacific Medical Center Research Institute shows interactions between capsaicin and cocaine that increase the lethality of cocaine many times over. In the experiments carried out, 10 mg / kg capsaicin was sufficient to increase the lethality of a dose of 60 mg / kg cocaine from 13 to 53%. These 10 mg / kg also caused an increase in mortality from 53 to 90% with a cocaine dose of 75 mg / kg. Mendelson points out that this may explain the deaths of people under the influence of drugs sprayed with pepper spray .

The news magazine Der Spiegel reported on three cases from Germany in which people under the influence of drugs were sprayed with pepper spray and died shortly afterwards. The cases strengthen the voices of critics who have long questioned the harmlessness of pepper sprays. The American civil rights association ACLU , for example, reports of 26 people who died between 1993 and 1995 in California alone who were sprayed with pepper spray before they died. Possible interactions with other psychotropic drugs or other drugs are also discussed. According to Spiegel , when the pepper sprays were introduced, authorities said that it was suitable for use against the mentally ill or drugged.

Use in equestrian sports

In the 2008 Olympic Games in China four were jumpers after a positive drug test suspended for the banned in equestrian sport capsaicin from the games of their horses, including the German Christian Ahlmann . The use of capsaicin on the horses' front legs makes them more sensitive to pain. As a result, you are more careful when jumping over the obstacles and no longer accept any obstacle contact. This is also known as a “chemical ingot ” and counted as doping .

In weight training

Since the use of capsaicin in humans has not yet been considered doping , its use as a dietary supplement has also been tested in humans (after rats and mice). The performance in repetitive squats was a highly significant 19% better in trained people than in a placebo, which also caused a burning sensation in the stomach.

literature

Omar ME Abdel-Salam (Ed.): Capsaicin as a Therapeutic Molecule. Springer, 2014. ISBN 978-3-0348-0827-9 (print); ISBN 978-3-0348-0828-6 (eBook).

Web links

www.wissenschaft.de: Deadly heat. Capsaicin kills prostate cancer cells in laboratory tests.
www.wissenschaft.de: With chilli against fat. Ingredient capsaicin kills fat cells in the test tube.

Individual evidence

^ Entry on FEMA 3404 in the database of the Flavor and Extract Manufacturers Association of the United States .
↑ Entry on CAPSAICIN in the CosIng database of the EU Commission, accessed on March 21, 2020.
↑ ^a ^b ^c data sheet (E) -Capsaicin (PDF) from Calbiochem, accessed on December 26, 2016.
↑ ^a ^b ^c ^d ^e ^f Entry on capsaicin. In: Römpp Online . Georg Thieme Verlag, accessed on May 14, 2014.
↑ ^a ^b ^c ^d The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 286, ISBN 978-0-911910-00-1 .
↑ ^a ^b data sheet capsaicin from Sigma-Aldrich , accessed on December 26, 2016 ( PDF ).
↑ Entry on capsaicin in the ChemIDplus database of the United States National Library of Medicine (NLM)
↑ Chili research: When it burns in the mouth , br.de, June 17, 2019.
↑ Too hot is not healthy - foods with very high capsaicin content can be harmful to your health. (PDF; 221 kB), BfR Opinion No. 053/2011 of October 18, 2011.
^ ^A ^b D. J. Bennett, Gordon William Kirby : Constitution and biosynthesis of capsaicin . In: J. Chem. Soc. C . 1968, p. 442-446 , doi : 10.1039 / j39680000442 (English).
↑ ^a ^b ^c ^d ^e ^f ^g Govindarajan, Sathyanarayana: Capsicum - Production, Technology, Chemistry, and Quality. Part V. Impact on Physiology, Pharmacology, Nutrition, and Metabolism; Structure, Pungency, Pain, and Desensitization Sequences . In: Critical Reviews in Food Science and Nutrition . tape 29 , no. 6 , 1991, pp. 435-474 (English).
↑ External identifiers or database links for capsazepine : CAS number: 138977-28-3, PubChem : 2733484 , ChemSpider : 2015280 , Wikidata : Q5036336 .
↑ Why chili peppers make you happy . World online ; Retrieved July 21, 2014.
↑ Chilli diet lowers blood pressure in rats . Spiegel Online . Retrieved August 4, 2010.
↑ University of Florida News: New research reveals why chili peppers are hot. ( Memento from September 23, 2008 in the Internet Archive ).
↑ JJ Tewksbury, KM Reagan, NJ Machnicki et al .: Evolutionary ecology of pungency in wild chilies. In: Proceedings of the National Academy of Sciences. 105, 2008, p. 11808, doi: 10.1073 / pnas.0802691105 .
↑ The wonderful heat of chillies - capsaicin as an answer to the concerted attacks of insects and fungi.
↑ Bugs put the heat in chili peppers. In: e! Science News. August 11, 2008.
↑ Mad Dog 357 No.9 Plutonium 9 Million Scoville Pepper Extract on scovilla.com.
↑ Zhou C, Ma D, Cao W, Shi H, Jiang Y: Fast simultaneous determination of capsaicin, dihydrocapsaicin and nonivamide for detecting adulteration in edible and crude vegetable oils by UPLC-MS / MS. , Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2018 Aug; 35 (8): 1447-1452, PMID 29601258
↑ Wang D, Meng F, Yu L, Sun L, Sun L, Guo J: A sensitive LC-MS / MS method for quantifying capsaicin and dihydrocapsaicin in rabbit plasma and tissue: application to a pharmacokinetic study. , Biomed Chromatogr. 2015 Apr; 29 (4): 496-503, PMID 25088519
↑ Zak A, Siwinska N, Slowikowska M, Borowicz H, Szpot P, Zawadzki M, Niedzwiedz A: The detection of capsaicin and dihydrocapsaicin in horse serum following long-term local administration. , BMC Vet Res. 2018 Jun 19; 14 (1): 193, PMID 29914499
↑ Rudolf Hänsel , Otto Sticher: Pharmakognosie - Phytopharmazie. 9th edition, Springer, 2010, ISBN 978-3-642-00962-4 , p. 1379.
↑ Some like it spicy (PDF; 6.75 MB), on application.wiley-vch.de, accessed on August 1, 2018, in Klaus Roth : Chemische Leckerbissen. Wiley-VCH, 2014 · ISBN 978-3-527-33739-2 , pp. 136-149.
↑ https://medlexi.de/Capsaicin
↑ Flavor Ordinance 1334/2008 (PDF)
↑ Oehme, P .: Capsaicin in local pain therapy. In: Deutsche Apothekerzeitung. No. 38, 2001, pp. 4457-4459.
↑ Onmeda: Capsaicin. Retrieved September 1, 2011.
↑ J. Schreiber, J. Slapke, K. Nieber and P. Oehme : Influence of capsaicin on the reactibility of the isolated guinea pig trachea. In: Biomed. Biochim. Acta. 49, 1990, pp. 97-101.
↑ Oehme, P. , I. Roske, W. Krause and E. Göres: Capsaicin - long-known natural substance with a new therapeutic perspective. In: drug therapy. Issue 12, 1993, 389-391.
↑ Entry on capsaicin in Pharmawiki , accessed on January 28, 2017.
↑ Therapy of neuropathic pain . ( Memento from July 27, 2014 in the Internet Archive ) (PDF) Guidelines of the Austrian Society for Neurology and DGN, 2008.
↑ Gerda Vacariu, Othmar Schuhfried, Marta Korpan: Physical therapy and rehabilitation for pain syndromes in the musculoskeletal system. In: Compendium of Physical Medicine and Rehabilitation. 3rd edition, 2013, ISBN 978-3-7091-0467-5 , p. 357.
↑ Madlaina Scharplatz: Does capsaicin relieve chronic pain? - Systematic review. (PDF; 108 kB). Retrieved September 1, 2011.
↑ Kerri Smith: Chili relieves pain. On: tagesspiegel.de. October 16, 2007, accessed September 1, 2011.
↑ René Buschow: The heterogeneity of TRPV1 and its activation in nociceptive neurons. Dissertation, FU Berlin, 2015. urn : nbn: de: kobv: 188-fudissthesis000000100196-5 .
↑ John E. Mendelson, Bryan K. Tolliver et al. a .: Capsaicin, an active ingredient in pepper sprays, increases the lethality of cocaine. In: Forensic Toxicology. 28, 2010, p. 33, doi: 10.1007 / s11419-009-0079-9 .
↑ ^a ^b Dangerous chilli mixture . In: Der Spiegel . No. 53 , 2009 ( online ).
↑ Possible interaction with drugs: deaths after use of pepper spray . In: Spiegel Online , December 26, 2009.
↑ German show jumper banned due to suspected doping. Retrieved August 21, 2008.
↑ Bars with chemistry. Retrieved August 22, 2008.
↑ Arnd Krüger : Capsaicin. In: competitive sport . 47 (6), 2017, pp. 34–35.
↑ M. Conrado de Freitas, JM Cholewa, RV Freire et al .: Acute capsaicin supplementation improves resistance training performance in trained men. In: Journal of strength and conditioning research. July 2017, doi: 10.1519 / JSC.0000000000002109 , PMID 28682933 .

[FEMA3404-1] Entry on FEMA 3404 in the database of the Flavor and Extract Manufacturers Association of the United States .

[CosIng-2] Entry on CAPSAICIN in the CosIng database of the EU Commission, accessed on March 21, 2020.

[Merck-3] ta sheet (E) -Capsaicin (PDF) from Calbiochem, accessed on December 26, 2016.

[roempp-4] ↑ ^a ^b ^c ^d ^e ^f Entry on capsaicin. In: Römpp Online . Georg Thieme Verlag, accessed on May 14, 2014.

[MerckIndex-5] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 286, ISBN 978-0-911910-00-1 .

[Sigma-6] ta sheet capsaicin from Sigma-Aldrich , accessed on December 26, 2016 ( PDF ).

[ChemIDplus-7] Entry on capsaicin in the ChemIDplus database of the United States National Library of Medicine (NLM)

[8] Chili research: When it burns in the mouth , br.de, June 17, 2019.

[9] Too hot is not healthy - foods with very high capsaicin content can be harmful to your health. (PDF; 221 kB), BfR Opinion No. 053/2011 of October 18, 2011.

[Bennett_Kirby_1968-10] A ^b D. J. Bennett, Gordon William Kirby : Constitution and biosynthesis of capsaicin . In: J. Chem. Soc. C . 1968, p. 442-446 , doi : 10.1039 / j39680000442 (English).

[Govindarajan_Sathyanarayana_1991-11] ↑ ^a ^b ^c ^d ^e ^f ^g Govindarajan, Sathyanarayana: Capsicum - Production, Technology, Chemistry, and Quality. Part V. Impact on Physiology, Pharmacology, Nutrition, and Metabolism; Structure, Pungency, Pain, and Desensitization Sequences . In: Critical Reviews in Food Science and Nutrition . tape 29 , no. 6 , 1991, pp. 435-474 (English).

[12] External identifiers or database links for capsazepine : CAS number: 138977-28-3, PubChem : 2733484 , ChemSpider : 2015280 , Wikidata : Q5036336 .

[13] Why chili peppers make you happy . World online ; Retrieved July 21, 2014.

[14] Chilli diet lowers blood pressure in rats . Spiegel Online . Retrieved August 4, 2010.

[15] University of Florida News: New research reveals why chili peppers are hot. ( Memento from September 23, 2008 in the Internet Archive ).

[16] JJ Tewksbury, KM Reagan, NJ Machnicki et al .: Evolutionary ecology of pungency in wild chilies. In: Proceedings of the National Academy of Sciences. 105, 2008, p. 11808, doi: 10.1073 / pnas.0802691105 .

[17] The wonderful heat of chillies - capsaicin as an answer to the concerted attacks of insects and fungi.

[18] Bugs put the heat in chili peppers. In: e! Science News. August 11, 2008.

[19] Mad Dog 357 No.9 Plutonium 9 Million Scoville Pepper Extract on scovilla.com.

[20] Zhou C, Ma D, Cao W, Shi H, Jiang Y: Fast simultaneous determination of capsaicin, dihydrocapsaicin and nonivamide for detecting adulteration in edible and crude vegetable oils by UPLC-MS / MS. , Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2018 Aug; 35 (8): 1447-1452, PMID 29601258

[21] Wang D, Meng F, Yu L, Sun L, Sun L, Guo J: A sensitive LC-MS / MS method for quantifying capsaicin and dihydrocapsaicin in rabbit plasma and tissue: application to a pharmacokinetic study. , Biomed Chromatogr. 2015 Apr; 29 (4): 496-503, PMID 25088519

[22] Zak A, Siwinska N, Slowikowska M, Borowicz H, Szpot P, Zawadzki M, Niedzwiedz A: The detection of capsaicin and dihydrocapsaicin in horse serum following long-term local administration. , BMC Vet Res. 2018 Jun 19; 14 (1): 193, PMID 29914499

[23] Rudolf Hänsel , Otto Sticher: Pharmakognosie - Phytopharmazie. 9th edition, Springer, 2010, ISBN 978-3-642-00962-4 , p. 1379.

[24] Some like it spicy (PDF; 6.75 MB), on application.wiley-vch.de, accessed on August 1, 2018, in Klaus Roth : Chemische Leckerbissen. Wiley-VCH, 2014 · ISBN 978-3-527-33739-2 , pp. 136-149.

[25] ttps://medlexi.de/Capsaicin

[26] Flavor Ordinance 1334/2008 (PDF)

[27] Oehme, P .: Capsaicin in local pain therapy. In: Deutsche Apothekerzeitung. No. 38, 2001, pp. 4457-4459.

[28] Onmeda: Capsaicin. Retrieved September 1, 2011.

[29] J. Schreiber, J. Slapke, K. Nieber and P. Oehme : Influence of capsaicin on the reactibility of the isolated guinea pig trachea. In: Biomed. Biochim. Acta. 49, 1990, pp. 97-101.

[30] Oehme, P. , I. Roske, W. Krause and E. Göres: Capsaicin - long-known natural substance with a new therapeutic perspective. In: drug therapy. Issue 12, 1993, 389-391.

[31] Entry on capsaicin in Pharmawiki , accessed on January 28, 2017.

[32] Therapy of neuropathic pain . ( Memento from July 27, 2014 in the Internet Archive ) (PDF) Guidelines of the Austrian Society for Neurology and DGN, 2008.

[33] Gerda Vacariu, Othmar Schuhfried, Marta Korpan: Physical therapy and rehabilitation for pain syndromes in the musculoskeletal system. In: Compendium of Physical Medicine and Rehabilitation. 3rd edition, 2013, ISBN 978-3-7091-0467-5 , p. 357.

[34] Madlaina Scharplatz: Does capsaicin relieve chronic pain? - Systematic review. (PDF; 108 kB). Retrieved September 1, 2011.

[35] Kerri Smith: Chili relieves pain. On: tagesspiegel.de. October 16, 2007, accessed September 1, 2011.

[36] René Buschow: The heterogeneity of TRPV1 and its activation in nociceptive neurons. Dissertation, FU Berlin, 2015. urn : nbn: de: kobv: 188-fudissthesis000000100196-5 .

[37] John E. Mendelson, Bryan K. Tolliver et al. a .: Capsaicin, an active ingredient in pepper sprays, increases the lethality of cocaine. In: Forensic Toxicology. 28, 2010, p. 33, doi: 10.1007 / s11419-009-0079-9 .

[spiegel.53/2009-38] Dangerous chilli mixture . In: Der Spiegel . No. 53 , 2009 ( online ).

[39] Possible interaction with drugs: deaths after use of pepper spray . In: Spiegel Online , December 26, 2009.

[40] German show jumper banned due to suspected doping. Retrieved August 21, 2008.

[41] Bars with chemistry. Retrieved August 22, 2008.

[42] Arnd Krüger : Capsaicin. In: competitive sport . 47 (6), 2017, pp. 34–35.

[43] M. Conrado de Freitas, JM Cholewa, RV Freire et al .: Acute capsaicin supplementation improves resistance training performance in trained men. In: Journal of strength and conditioning research. July 2017, doi: 10.1519 / JSC.0000000000002109 , PMID 28682933 .