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

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 possess anti-inflammatory, neuroprotective, and analgesic effects, either alone or in combination with other cannabis components. This review synthesizes indexed literature on the phytochemistry, pharmacodynamics, pharmacokinetics, and potential therapeutic uses of CBG and CBGA. This review emphasizes recent advances in extraction 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 data support 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 of crossing the blood-brain barrier, with detectable concentrations in plasma and brain tissue following both oral and 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 absorption kinetics 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, their implementation 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, the lack of comprehensive pharmacokinetic data and randomized clinical trials evaluating CBG or CBGA as isolated compounds with primary endpoints reveals a significant translational gap that currently hinders rational clinical development. This review integrates current findings in phytochemistry, analytical chemistry, pharmacology, and clinical science, offering a comprehensive perspective on the development of CBG-based and full-spectrum cannabis products for medical use.