Caryophyllene /ˌkærioʊfɪˈliːn/, 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 9-membered ring, both rarities in nature.
The approximate quantity of caryophyllene in the essential oil of each source is given in square brackets ([ ]):
- Cannabis, hemp, marijuana (Cannabis sativa) [3.8–37.5% of cannabis flower essential oil]
- Black caraway (Carum nigrum) [7.8%]
- Cloves (Syzygium aromaticum) [1.7–19,5% of clove bud essential oil]
- Hops (Humulus lupulus) [5.1–14.5%]
- Basil (Ocimum spp.) [5.3–10.5% O. gratissimum; 4.0–19.8% O. micranthum]
- Oregano (Origanum vulgare) [4.9–15.7%]
- Black pepper (Piper nigrum) [7.29%]
- Lavender (Lavandula angustifolia) [4.62–7.55% of lavender oil]
- Rosemary (Rosmarinus officinalis) [0.1–8.3%]
- True cinnamon (Cinnamomum zeylanicum) [6.9–11.1%]
- Malabathrum (Cinnamomum tamala) [25.3%]
- Ylang-ylang (Cananga odorata) [3.1–10.7%]
- Copaiba oil (Copaifera spp.)
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. Whether this compound is able to modulate inflammatory processes in humans via the endocannabinoid system is yet unknown. However, it is found to elicit significant neuroprotection by its anti-inflammatory and antioxidant activities mediated by activation of the CB2 receptors in rats. Caryophyllene does not bind to the centrally expressed cannabinoid receptor type-1 (CB1) and therefore does not exert psychoactive effects. However, phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus) are found. Scientific evidence have been presented for non-cannabinoid plant components as putative antidotes to intoxicating effects of THC (C21H30O2), that could increase its therapeutic index.