CARYOPHYLLENE EFFECTS ON CANNABINOID RECEPTORS
Jürg Gertsch and others in 2008 reported plant-derived β-caryophyllene selectively binds to CB2 receptors and is a functional CB2 agonist. They provided evidence it exerts cannabi-mimetic effects in vivo by reducing inflammatory response in wild-type mice but not in mice lacking CB2 receptors. β-caryophyllene was identified as a functional non-psychoactive CB2 receptor ligand and as an anti-inflammatory cannabinoid in cannabis.
In addition to the wide range of CB1 receptor-mediated physiological effects on the central nervous system, CNS, different cannabinoid ligands have been reported to modulate immune responses. CB2 receptor ligands have been shown to inhibit inflammation and edema, exert analgesic effects, and have a protective role in ischemia-reperfusion injury. In the gastrointestinal tract, CB2 receptor agonists have been shown to prevent colitis by reducing inflammation. The CB2 receptor has been described as a potential target for the treatment of atherosclerosis and osteoporosis. Consequently, CB2 receptor-selective agonists, being devoid of psychoactive side effects typically associated with CB1 receptor activation, are potential drug candidates for a wide range of different disease states.
β-caryophyllene is commonly ingested with vegetable foods, particularly black pepper. Accordingly, adequate daily intake of caryophyllene could potentially modulate inflammatory and other pathophysiological processes via the endocannabinoid system and help maintain health. The potential of β-caryophyllene in both human and animal health needs further investigation as much of the focus of cannabinoids has been on cannabis and cannabidiol, CBD. As a selective agonist of cannabinoid receptor type-2 (CB2), caryophyllene has been shown to exert significant cannabi-mimetic anti-inflammatory effects. Anti-nociceptive, neuroprotective, anxiolytic, antidepressant, and anti-alcoholism activities have also been reported in vitro and in rodent studies.
β-Caryophyllene has the distinction of being the first known “dietary cannabinoid,” a common component of food that has GRAS (Generally Recognized as Safe) status and is approved by the FDA for food use. β-Caryophyllene is the primary sesquiterpene contributing to the spiciness of black pepper; it is also a major constituent of cloves, hops, rosemary, copaiba, and cannabis.
It was one of the first cannabis-derived compounds other than THC, CBD, and CBN shown to bind directly to endocannabinoid receptors (Gertsch, 2008). In fact, it was one of the first cannabis-derived compounds with a fundamentally different structure from the classical cannabinoids that interacts with the endocannabinoid system in humans. β-Caryophyllene is known to selectively bind to the CB2 receptor; therefore, it is sometimes also classed as an atypical cannabinoid (Gertsch et al., 2010).
CB1 is responsible for the psychoactive effects associated with certain cannabinoids such as THC. However, CB2, particularly in peripheral tissues in the body, is a therapeutic target for treatment of inflammation, pain, atherosclerosis, and osteoporosis (Gertsch, 2008; Gertsch et al., 2008). β-Caryophyllene has now been shown to be directly beneficial for:
colitis (Bento et al.,2011), osteoarthritis (Rufino et al., 2015), diabetes (Basha and Sankaranarayanan, 2014), cerebral ischemia (Chang et al., 2013), anxiety and depression (Bahi et al., 2014), liver fibrosis (Calleja et al., 2013; Mahmoud et al., 2014), and Alzheimer-like disease types (Cheng et al., 2014).
In cancer studies, β-caryophyllene demonstrated synergy with the chemotherapy drug Paclitaxel on human tumor cell lines, and alone it stimulates apoptosis and suppresses tumor growth (Legault and Pichette, 2007). In a Caenorhabditis elegans model, β-caryophyllene modulated stress-related genes and extended the lifespan of the organism (Pant et al., 2014). Importantly, it has been shown to be orally bioavailable; therefore, it would provide an important medicinal benefit to oral cannabis preparations.