Caryophyllene

β-Caryophyllene (trans-(1R,9S)-4,11,11-trimethyl-8-methylenebicyclo[7.2.0]undec-4-ene; C₁₅H₂₄) is a bicyclic sesquiterpene with a peppery, woody aroma, abundant in black pepper, cloves, and many cannabis cultivars. Gertsch et al. (2008, PNAS 105:9099) showed that β-caryophyllene is a selective CB2 receptor agonist (Ki ≈ 155 nM) with no meaningful CB1 activity — making it the only known dietary cannabinoid and a legitimate bridge between the "terpene" and "cannabinoid" categories. Because it does not activate CB1, β-caryophyllene is non-intoxicating. Preclinical studies demonstrate anti-inflammatory, analgesic, anxiolytic, and hepatoprotective effects in rodent models. Caryophyllene oxide is an oxidized derivative important in forensic detection. Evidence level: robust in vitro receptor pharmacology, extensive rodent data, emerging small human studies. → See also: CB2 receptor, Terpene, Terpenoid.