Caryophyllene (Template:IPAc-en), more formally (−)-β-caryophyllene (BCP), is a natural bicyclic sesquiterpene that occurs widely in nature. Caryophyllene is notable for having a cyclobutane ring, as well as a trans-double bond in a 9-membered ring, both rarities in nature.[1]
Caryophyllene can be produced synthetically,[2] but it is invariably obtained from natural sources because it is widespread. It 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, copaiba, rosemary, and hops.[1] 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 one of the chemical compounds that contributes to the aroma of black pepper.[3]
Basic research
β-Caryophyllene is under basic research for its potential action as an agonist of the cannabinoid receptor type 2 (CB2 receptor).[4] In other basic studies, β-caryophyllene has a binding affinity of Ki = 155 nM at the CB2 receptors.[5]
β-Caryophyllene has the highest cannabinoid activity compared to the ring opened isomer α-caryophyllene humulene which may modulate CB2 activity.[6] To compare binding, cannabinol binds to the CB2 receptors as a partial agonist with an affinity of Ki = 126.4 nM,[7] while delta-9-tetrahydrocannabinol binds to the CB2 receptors as a partial agonist with an affinity of Ki = 36 nM.[8]
Safety
Caryophyllene has been given generally recognized as safe (GRAS) designation by the FDA and is approved by the FDA for use as a food additive, typically for flavoring.[9][10] Rats given up to 700 mg/kg daily for 90 days did not produce any significant toxic effects.[11] Caryophyllene has an LD50 of 5,000 mg/kg in mice.[12][13]
Metabolism and derivatives
14-Hydroxycaryophyllene oxide (C15H24O2) was isolated from the urine of rabbits treated with (−)-caryophyllene (C15H24). The X-raycrystal structure of 14-hydroxycaryophyllene (as its acetate derivative) has been reported.[14]
The metabolism of caryophyllene progresses through (−)-caryophyllene oxide (C15H24O) since the latter compound also afforded 14-hydroxycaryophyllene (C15H24O) as a metabolite.[15]
Caryophyllene oxide,[16] in which the alkene group of caryophyllene has become an epoxide, is the component responsible for cannabis identification by drug-sniffing dogs[17][18] and is also an approved food additive, often as flavoring.[10] Caryophyllene oxide may have negligible cannabinoid activity.[19]
Natural sources
The approximate quantity of caryophyllene in the essential oil of each source is given in square brackets ([ ]):
