Capsaicin and several related amides (capsaicinoids) are produced as secondary metabolites by chili peppers, likely as deterrents against certain mammals and fungi.

[2] 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.

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 disperse.

[13] Because of the burning sensation caused by capsaicin when it comes in contact with mucous membranes, it is commonly used in food products to provide added spiciness or "heat" (piquancy), usually in the form of spices such as chili powder and paprika.

[14] Folklore among self-described "chiliheads" attribute this to pain-stimulated release of endorphins, a different mechanism from the local receptor overload that makes capsaicin effective as a topical analgesic.

[16] It may be applied in cream form for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, backache, strains and sprains, often in compounds with other rubefacients.

[25] There is insufficient clinical evidence to determine the role of ingested capsaicin on several human disorders, including obesity, diabetes, cancer and cardiovascular diseases.

[2] When the spray comes in contact with skin, especially eyes or mucous membranes, it produces pain and breathing difficulty in the affected individual.

Targets of capsaicin repellants include voles, deer, rabbits, squirrels, bears, insects, and attacking dogs.

[26] Ground or crushed dried chili pods may be used in birdseed to deter rodents,[27] taking advantage of the insensitivity of birds to capsaicin.

[30] At the show jumping events of the 2008 Summer Olympics, four horses tested positive for capsaicin, which resulted in disqualification.

[40] Even healthy young people can suffer adverse health effects like myocardial infarction after ingestion of capsaicin capsules.

[41] The burning and painful sensations associated with capsaicin result from "defunctionalization" of nociceptor nerve fibers by causing a topical hypersensitivity reaction in the skin.

[42][43][44] TRPV1, which can also be stimulated with heat, protons and physical abrasion, permits cations to pass through the cell membrane when activated.

[47][a] In 1873 German pharmacologist Rudolf Buchheim[57][58][59] (1820–1879) and in 1878 the Hungarian doctor Endre Hőgyes[60][61] stated that "capsicol" (partially purified capsaicin[62]) caused the burning feeling when in contact with mucous membranes and increased secretion of gastric acid.

Although vanillylamide of n-nonanoic acid (Nonivamide, VNA, also PAVA) is produced synthetically for most applications, it does occur naturally in Capsicum species.

[65][66] Enzymes of the phenylpropanoid 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.,[67][68] and Sukrasno and Yeoman.

[70] 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.

[72] Capsaicin is believed to be synthesized in the interlocular septum of chili peppers and depends on the gene AT3, which resides at the pun1 locus, and which encodes a putative acyltransferase.

Additionally, the ergosterol synthesis of growing fungi decreases in relation to the amount of capsaicin present in the growth area.

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.

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.