Cannabinoid receptor 1 and 2 (CB1/CB2)

Cannabinoid receptors 1 (CB1) and 2 (CB2) are integral membrane proteins belonging to the G protein-coupled receptor (GPCR) superfamily and serve as the primary mediators of the endocannabinoid system. CB1 is predominantly localized in the central nervous system, where it regulates the release of neurotransmitters such as GABA and glutamate, while CB2 is primarily expressed in immune cells and peripheral tissues, governing anti-inflammatory and immunomodulatory pathways (UniProt P21554, P34972). These receptors are critical therapeutic targets for managing chronic pain, epilepsy, and spasticity associated with multiple sclerosis. Recent pharmacological research has highlighted the role of d-limonene, a common terpene, as a selective agonist for the CB2 receptor and a modulator of CB1 activity (Raz et al., 2024). In clinical contexts, d-limonene has been shown to reduce the anxiety-inducing effects of THC, suggesting a synergistic "entourage effect" that enhances the therapeutic window of cannabinoid-based medicines (Clow et al., 2024). Understanding the interplay between these receptors and non-cannabinoid ligands like d-limonene is essential for developing next-generation analgesics and anxiolytics with reduced side-effect profiles.

Other names

CNR1CNR2CB1RCB2RCannabinoid receptor type 1Cannabinoid receptor type 2Central cannabinoid receptorPeripheral cannabinoid receptor

Cannabinoid receptors function as G protein-coupled receptors (GPCRs) that, upon activation by agonists, inhibit adenylyl cyclase activity and modulate calcium and potassium channels to regulate neurotransmitter release and inflammatory cytokine production. D-limonene specifically has been identified as a selective CB2 receptor agonist and a functional modulator that can mitigate CB1-mediated anxiety responses induced by THC.