Cannabichromene is a cannabinoid CB₂ receptor agonist

Abstract

Background and Purpose: Cannabichromene (CBC) is one of the most abundant phytocannabinoids in Cannabis spp. It has modest antinociceptive and antiinflammatory effects and potentiates some effects of Δ 9-tetrahydrocannabinol in vivo. How CBC exerts these effects is poorly defined and there is little information about its efficacy at cannabinoid receptors. We sought to determine the functional activity of CBC at cannabinoid CB 1 and CB 2 receptors. Experimental Approach: AtT20 cells stably expressing haemagglutinin-tagged human CB 1 and CB 2 receptors were used. Assays of cellular membrane potential and loss of cell surface receptors were performed. Key Results: CBC activated CB 2 but not CB 1 receptors to produce hyperpolarization of AtT20 cells. This activation was inhibited by a CB 2 receptor antagonist AM630, and sensitive to Pertussis toxin. Application of CBC reduced activation of CB 2 , but not CB 1 , receptors by subsequent co-application of CP55,940, an efficacious CB 1 and CB 2 receptor agonist. Continuous CBC application induced loss of cell surface CB 2 receptors and desensitization of the CB 2 receptor-induced hyperpolarization. Conclusions and Implications: CBC is a selective CB 2 receptor agonist displaying higher efficacy than tetrahydrocannabinol in hyperpolarizing AtT20 cells. CBC can also recruit CB 2 receptor regulatory mechanisms. CBC may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB 2 receptor-mediated modulation of inflammation. 1 | INTRODUCTION Cannabichromene (CBC) is one of over 100 phytochemicals (collectively referred to as phytocannabinoids) that are found in Cannabis spp (ElSohly & Gul, 2014). CBC was identified in 1966 and is one of the most abundant phytocannabinoids alongside Δ 9-tetrahydrocannabinol (THC),

Naturally Occurring Cannabinoids and their Role in Modulation of Cardiovascular Health

“…CBC is a phytocannabinoid present at lower concentration in Cannabis sativa, and is a CB2 receptor and TRP subfamily A, member 1 (TRPA1) agonist (Romano et al 2013;Udoh et al 2019), with demonstrated anti-inflammatory, anti-fungal, and anti-bacterial activity (Russo 2011). In rat, CBC appears to have potential for hypotensive effect with additional reduction in respiratory rate and a potentiation of the reduced heart rate seen with THC administration (O'Neil et al 1979).…”

Bioactive Chemical Composition of Cannabis Extracts and Cannabinoid Receptors

“…The rationale for selecting the CBD and ∆ 9 -THC compound families as independent variables lies in their relative abundance because total CBD and ∆ 9 -THC concentrations in the cannabis plant are generally many times higher than those of other phytocannabinoids [41] and are, thus, thought to be the primary determinants of cannabinoid receptors activities. However, complex natural products such as cannabis can contain up to hundreds of unique compounds, and it remains unknown how less abundant phytocannabinoids, such as cannabichromene (CBC) and cannabigerol (CBG), affect the activity of cannabis extracts at cannabinoid receptors [42,43].…”

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

“…Cannabichromene is an agonist of the TRPA1 channels; it might block TPRM8 and activate the TRPV3 and TRPV4 channels. Its affinity for cannabinoid receptors is low, it is a selective CB 2 receptor agonist, and it can also recruit CB 2 receptor regulatory mechanisms [ 52 , 69 ]. The antibiotic, antifungal, anti-inflammatory, and analgesic effects of cannabichromene are noticed [ 69 ].…”