Capsaicin

Capsaicin is the compound that makes chili peppers hot, a natural irritant that activates the heat-sensing TRPV1 channel on sensory nerves.

When applied to skin, capsaicin first causes burning and redness as TRPV1 fires, then, with repeated exposure, the nerve endings become desensitized and less able to transmit pain signals from the area. That two-phase action is the basis for over-the-counter capsaicin creams and for a high-concentration prescription patch used for certain nerve pain. It is also used in animal and human research as a reliable way to produce controlled, temporary pain and sensitization.

Capsaicin appears in some cannabinoid topicals as a warming ingredient, where it produces a noticeable heat sensation that consumers often mistake for the cannabinoid working. Its relevance to cannabinoid science is mechanistic: cannabidiol acts on the same TRPV1 channel in laboratory studies, and capsaicin-induced pain models are used to test cannabinoids in early trials. Capsaicin is kept away from eyes and mucous membranes, and topicals containing it are not meant for broken skin.