Cannabidiol target sites (multiple targets) (CBD targets)

Cannabidiol (CBD) is a phytocannabinoid derived from *Cannabis sativa* that interacts with a remarkably diverse array of molecular targets, including over 60 known binding sites spanning G protein-coupled receptors, ion channels, enzymes, and nuclear receptors. Unlike THC, CBD exhibits very low affinity for the classical cannabinoid receptors CB1 and CB2 but instead acts as a multimodal pharmacological agent, functioning as a negative allosteric modulator of CB1/CB2, a partial agonist at GPR18, an antagonist of GPR55, and a direct agonist at serotonin receptors (5-HT1A, 5-HT2A) and glycine receptors.[1][5] CBD also inhibits the endocannabinoid-metabolizing enzyme FAAH, binds to the vanilloid receptor VR1/TRPV1, modulates voltage-gated and transient receptor potential ion channels, and activates the nuclear receptor PPARγ.[3][5] This polypharmacological profile underlies CBD's potential therapeutic applications in diverse conditions including epilepsy, neuropathic pain, inflammation, cancer, and psychiatric disorders, though clinical translation of preclinical target interactions remains limited. Significant drug-drug interaction potential exists due to CBD's inhibition of multiple cytochrome P450 isoforms, which may complicate its use in polypharmacy scenarios.[5] The structural similarity of CBD to other minor cannabinoids determines binding pattern clustering, with recent molecular docking studies identifying GTPase KRas and hematopoietic cell kinase (HCK) as novel high-affinity targets with potential in cancer and inflammatory diseases.[1]

Other names

CBDCannabidiol molecular targetsCBD target profileEndocannabinoid system modulators (functional classification)

CBD's mechanisms of action vary by target: Negative allosteric modulation of CB1 and CB2 receptors; Partial agonism/antagonism at GPCR targets (GPR18, GPR55); Direct agonism at serotonin receptors and glycine receptors; Enzyme inhibition (FAAH, COX1, select CYP450 isoforms, aldose reductase); Ion channel modulation (activation of TRPA1, inhibition of T-type calcium channels and NMDA receptors); Nuclear receptor activation (PPARγ translocation and transcriptional activity). Notably, CBD's partial agonism at GPR18 maintains stable conformations, whereas THC's full agonism generates "metastable" conformations with mechanical constraints in the receptor's active pocket.