Capsaicin
8-Methyl-N-vanillyl-trans-6-nonenamide
Other names (E)-N-(4-Hydroxy-3-methoxybenzyl) -8-methylnon-6-enamide, trans-8-Methyl-N-vanillylnon -6-enamide, (E)-Capsaicin, Capsicine, Capsicin, CPS, C

Capsaicin

Heat	Above Peak (SR: 15,000,000-16,000,000)

Capsaicin (pron.: /kæpˈseɪ.ɨsɪn/; 8-methyl-N-vanillyl-6-nonenamide, ( (CH₃)₂CHCH=CH(CH₂)₄CONHCH₂C₆H₃-4-(OH)-3-(OCH₃) ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. Capsaicin and several related compounds are called capsaicinoids and are produced as secondary metabolites by chili peppers, probably as deterrents against certain mammals and fungi.^[2] Pure capsaicin is a volatile, hydrophobic, colorless, odorless, crystalline to waxy compound.

The compound was first extracted (albeit in impure form) in 1816 by Christian Friedrich Bucholz (1770–1818). He called it “capsicin,” after the genus Capsicum from which it was extracted. John Clough Thresh (1850–1932), who had isolated capsaicin in almost pure form, gave it the name “capsaicin” in 1876. But it was Karl Micko who first isolated capsaicin in pure form in 1898. Capsaicin’s empirical formula (chemical composition) was first determined by E. K. Nelson in 1919; he also partially elucidated capsaicin’s chemical structure. Capsaicin was first synthesized in 1930 by E. Spath and S. F. Darling.In 1961, similar substances were isolated from chili peppers by the Japanese chemists S. Kosuge and Y. Inagaki, who named them capsaicinoids.

In 1873 German pharmacologist Rudolf Buchheim(1820–1879) and in 1878 the Hungarian doctor Endre Hőgyesstated that “capsicol” (partially purified capsaicin) caused the burning feeling when in contact with mucous membranes and increased secretion of gastric juice.

Capsaicin is the main capsaicinoid in chili peppers, followed by dihydrocapsaicin. These two compounds are also about twice as potent to the taste and nerves as the minor capsaicinoids nordihydrocapsaicin, homodihydrocapsaicin, and homocapsaicin. Dilute solutions of pure capsaicinoids produced different types of pungency; however, these differences were not noted using more concentrated solutions.

Capsaicin is believed to be synthesized in the interlocular septum of chili peppers by addition of a branched-chain fatty acid to vanillylamine; specifically, capsaicin is made from vanillylamine and 8-methyl-6-nonenoyl CoA. Biosynthesis depends on the gene AT3, which resides at the pun1 locus, and which encodes a putative acyltransferase.

Besides the six natural capsaicinoids, one synthetic member of the capsaicinoid family exists. Vanillylamide of n-nonanoic acid (VNA, also PAVA) is used as a reference substance for determining the relative pungency of capsaicinoids.

Capsaicinoid name	Abbrev.	Typical relative amount	Scoville heat units	Chemical structure
Capsaicin	C	69%	16,000,000
Dihydrocapsaicin	DHC	22%	15,000,000
Nordihydrocapsaicin	NDHC	7%	9,100,000
Homodihydrocapsaicin	HDHC	1%	8,600,000
Homocapsaicin	HC	1%	8,600,000
Nonivamide	PAVA		9,200,000

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 fruits of plants in the genus Capsicum. 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.

The seeds of Capsicum plants are predominantly dispersed by birds. The TRPV1 channel to which capsaicin binds does not respond to capsaicin and related chemicals in birds (avian vs mammalian TRPV1 show functional diversity and selective sensitivity). Chili pepper seeds consumed by birds pass through the digestive tract and can germinate later, but mammals have molar teeth, which destroy seeds and prevent them from germinating. 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.In addition, there is evidence that capsaicin evolved as an anti-fungal agent. The fungal pathogen, Fusarium, is known to infect wild chilies which reduces seed viability. Capsaicin deters the fungus, and in doing so limits this form of predispersal seed mortality.

In 2006, it was discovered that the venom of a certain tarantula species 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.

Food

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” (piquancy). 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 Scoville scale. In some cases people enjoy the heat; there has long been a demand for capsaicin-spiced food and beverages. There are many cuisines and food products featuring capsaicin such as hot sauce, salsa, and beverages.

For information on treatment, see the section Treatment after exposure.

It is common for people to experience pleasurable and even euphoriant effects from ingesting capsaicin. Folklore among self-described “chiliheads” attributes this to pain-stimulated release of endorphins, 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 naloxone and other compounds that compete for receptor sites with endorphins and opiates.

Capsaicin is currently used in topical ointments, as well as a high-dose dermal patch (trade name Qutenza), to relieve the pain of peripheral neuropathy such as post-herpetic neuralgia caused by shingles It may be used in concentrations of between 0.025% and 0.25%. It may be used as a cream for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains and sprains, often in compounds with other rubefacients.^[The treatment typically involves the application of a topical anesthetic until the area is numb. Then the capsaicin is applied by a therapist wearing rubber gloves 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 bandages (plasters) that can be applied to the back.

Capsaicin creams are used to treat psoriasis as an effective way to reduce itching and inflammation

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 carbohydrates breakdown after a meal, cayenne may also be used to regulate blood sugar levels

Capsaicin selectively binds to a protein known as TRPV1 that resides on the membranes of pain and heat sensing neurons TRPV1 is a heat activated calcium channel, which opens between 37 and 45 °C (98.6 and 113 °F, respectively). When capsaicin binds to TRPV1, it causes the channel to open below 37 °C (normal human body temperature), which is why capsaicin is linked to the sensation of heat. Prolonged activation of these neurons by capsaicin depletes presynaptic substance P, one of the body’s neurotransmitters for pain and heat. Neurons that do not contain TRPV1 are unaffected.

The result appears to be that the chemical mimics a burning sensation, the nerves are overwhelmed by the influx, and are unable to report pain for an extended period of time. With chronic exposure to capsaicin, neurons are depleted of neurotransmitters, leading to reduction in sensation of pain and blockade of neurogenic inflammation. If capsaicin is removed, the neurons recover.

The American Association for Cancer Research reports studies suggesting capsaicin is able to kill prostate cancer and lung cancer cells by causing them to undergo apoptosis.The studies were performed on tumors formed by human prostate cancer cell cultures grown in mouse models, and showed tumors treated with capsaicin were about one-fifth the size of the untreated tumors. There have been several mouse studies conducted in Japan and China that showed natural capsaicin directly inhibits the growth of leukemic cells. Capsaicin may be able to trigger apoptosis in human lung cancer cells as well.

Capsaicin is also the key ingredient in the experimental drug Adlea, which is in Phase 2 trials as a long-acting analgesic to treat post-surgical and osteoarthritic pain for weeks to months after a single injection to the site of pain. Moreover, it reduces pain resulting from rheumatoid arthritis as well as joint or muscle pain from fibromyalgia or other causes.

Less-lethal force

Capsaicin is also the active ingredient in riot control and personal defense pepper spray chemical agents. When the spray comes in contact with skin, especially eyes or mucous membranes, 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 Scoville scale for a comparison of pepper spray to other sources of capsaicin.

In large quantities, capsaicin can cause death. 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 chillies make the risk of accidental poisoning by chilli consumption negligible.