(-)-β-caryophyllene

Caryophyllene , or (−)-β-caryophyllene, 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 an 8-membered ring, both rarities in nature.
Caryophyllene is one of the chemical compounds that contributes to the spiciness of black pepper. Caryophyllene was shown to be selective agonist of cannabinoid receptor type-2 (CB2) and to exert significant cannabimimetic antiinflammatory effects in mice. Antinociceptive, neuroprotective, anxiolytic and antidepressant and anti-alcoholism activity in in vitro studies and in rodent models have been reported. Because caryophyllene is an FDA-approved food additive and ingested daily with food, it is the first dietary cannabinoid. Whether this compound is able to modulate inflammatory processes in humans via the endocannabinoid system is yet unknown. Caryophyllene does not bind to the centrally expressed cannabinoid receptor type-1 (CB1) and therefore does not exert psychoactive effects.
The first total synthesis of caryophyllene in 1964 by E.J. Corey was considered one of the classic demonstrations of the possibilities of synthetic organic chemistry at the time.; Caryophyllene oxide, in which the olefin of caryophyllene has become an epoxide, is the component responsible for cannabis identification by drug-sniffing dogs and is also an approved food flavoring.