Caryophyllene

Caryophyllene (ˌkærioʊ-ˈfɪliːn), more formally (−)-β-caryophyllene, (BCP), is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of Syzygium aromaticum (cloves), the essential oil of Cannabis sativa, rosemary, and hops. It is usually found as a mixture with isocaryophyllene (the cis double bond isomer) and α-humulene (obsolete name: α-caryophyllene), a ring-opened isomer. Caryophyllene is notable for having a cyclobutane ring, as well as a trans-double bond in a 9-membered ring, both rarities in nature. Caryophyllene is one of the chemical compounds that contributes to the aroma of black pepper. β-Caryophyllene acts as a full agonist of the Cannabinoid receptor type 2 (CB2 receptor) in rats. β-Caryophyllene has a binding affinity of Ki = 155nM at the CB2 receptors in mice. β-Caryophyllene has been shown to have anti-inflammatory action linked to its CB2 receptor activity in a study comparing the pain killing effects in mice with and without CB2 receptors with the group of mice without CB2 receptors seeing little benefit compared to the mice with functional CB2 receptors. β-Caryophyllene has the highest cannabinoid activity compared to the ring opened isomer α-caryophyllene Humulene which may modulate CB2 activity. To compare binding, Cannabinol (CBN) binds to the CB2 receptors as a partial agonist with an affinity of CB2 Ki = 126.4 nM while Delta-9-Tetrahydrocannabinol binds to the CB2 receptors as a partial agonist with an affinity of Ki = 36nM. Caryophyllene helps to improve cold tolerance at low ambient temperatures. Wild giant pandas frequently roll in horse manure, which contains beta-caryophyllene/caryophyllene oxide, to inhibit transient receptor potential melastatin 8 (TRPM8), an archetypical cold-activated ion channel of mammals. ß-caryophyllene could be efficiently used in the fight against cancer. For example, in an in vitro human colorectal adenocarcinoma study β-caryophyllene used alone did not inhibited cancer cell growth, but a combination of β-caryophyllene 10 μg/mL−1 and Paclitaxel 0.