Cannabigerol and cannabigerolic acid: Biosynthesis, pharmacology, and translational perspectives. A critical review

Abstract

Cannabigerol (CBG), in its neutral and acidic forms (CBGA), is emerging as a key non-psychoactive phyto­cannabinoid with distinctive pharmacological properties. While most research to date has focused on cannabidiol(CBD) and Δ9-tetrahydrocannabinol (THC), recent peer-reviewed studies suggest that CBG and CBGA possessanti-inflammatory, neuroprotective, and analgesic effects, either alone or in combination with other cannabiscomponents. This review synthesizes indexed literature on the phytochemistry, pharmacodynamics, pharma­cokinetics, and potential therapeutic uses of CBG and CBGA. This review emphasizes recent advances inextraction techniques aimed at selectively enriching CBG content from Cannabis sativa chemovars bred for high-CBG profiles. Analytical methodologies are critically reviewed, highlighting challenges in distinguishing CBG/CBGA from structurally similar cannabinoids in full-spectrum extracts.Additionally, studies exploring the therapeutic potential of combining CBG with other cannabinoids in full-spectrum extracts are discussed, revealing synergistic interactions. Preliminary clinical and preclinical datasupport the inclusion of CBG in medical cannabis formulations, although further toxicological and pharmaco­kinetic data are required to establish its safety profile and regulatory acceptance, since data on its pharmaco­kinetic profile remain limited. Preclinical studies have shown that CBG is orally bioavailable and capable ofcrossing the blood-brain barrier, with detectable concentrations in plasma and brain tissue following eboth oraland intraperitoneal administration in rodents. Early-stage human studies evaluating full-spectrum cannabis ex­tracts have detected measurable levels of CBG in plasma following oral administration, although its absorptionkinetics are still poorly characterized. Further pharmacokinetic studies in humans are needed to determine dose-exposure relationships, bioavailability across different delivery routes, metabolic pathways, and potential drug-drug interactions, particularly given the increasing inclusion of CBG in medicinal cannabis formulations.Although preclinical studies consistently demonstrate the pharmacological versatility of CBG and CBGA, theirimplementation in the clinical context remains restricted.The available data in humans are largely limited to pilot or exploratory studies, which often include multi-cannabinoid formulations and prioritize safety assessment over conclusive efficacy results. Furthermore, thelack of comprehensive pharmacokinetic data and randomized clinical trials evaluating CBG or CBGA as isolatedcompounds with primary endpoints reveals a significant translational gap that currently hinders rational clinicaldevelopment.This review integrates current findings in phytochemistry, analytical chemistry, pharmacology, and clinicalscience, offering a comprehensive perspective on the development of CBG-based and full-spectrum cannabisproducts for medical use.