Cannabigerol (CBG)

Cannabigerol (CBG) is a non-intoxicating phytocannabinoid often called the 'mother cannabinoid': its acidic form CBGA is the biosynthetic precursor from which the cannabis plant makes THCA, CBDA and CBCA, so mature plants usually retain only ~1% CBG. Unlike THC it does not meaningfully activate brain CB1. It binds both cannabinoid receptors only weakly (CB1 Ki ≈380–2600 nM, CB2 ≈150–3500 nM, several-fold weaker than THC) and behaves there as a weak partial agonist/antagonist, which is why it produces no cannabis-like 'high'. CBG's most distinctive actions are outside the cannabinoid receptors: it is a highly potent α2-adrenoceptor agonist and a moderately potent 5-HT1A receptor antagonist. The α2 agonism (clonidine-like) can lower heart rate and blood pressure and cause sedation, while the 5-HT1A antagonism means CBG can oppose some 5-HT1A-mediated effects, including those of CBD. It also modulates several ion channels: a potent TRPM8 antagonist, a weak agonist at TRPA1 and TRPV1–4, and a blocker of voltage-gated sodium channels (Nav1.7, Nav1.8 and others), the basis of investigational analgesic interest. Additional reported actions include weak PPARγ agonism, inhibition of anandamide reuptake/metabolism, and weak COX inhibition. CBG is highly lipophilic (logP ~7) and, like other cannabinoids, is hepatically metabolised (CYP-mediated, e.g. CYP2J2). Human pharmacokinetic and clinical data are very limited. Its poor metabolic/PK properties have hindered drug development, and essentially all efficacy evidence to date is preclinical (cell and animal models).