Cannabigerol at the Interface of the Gut Microbiota and EndoCannabinoidome: Mechanistic Insights into Inflammation and Pain Modulation.

Castañeda-Ruelas G.; Grijalva-Contreras L.; Quiñonez-Bastidas G. · Medical sciences (Basel, Switzerland) · 2026

**Background & Methods** This is a narrative review article examining the role of cannabigerol (CBG), a non-psychotropic phytocannabinoid, at the interface between gut microbiota and the endocannabinoidome (eCBome) in modulating inflammation and pain. The authors synthesized recent literature on CBG's pharmacological mechanisms and its potential therapeutic applications for chronic inflammatory and pain conditions. **Key Findings** - CBG activates multiple receptor systems (CB2, PPARs, TRPV1, TRPA1, and α2-adrenergic receptors) while suppressing pro-inflammatory mediators including TNF-α, COX-2, iNOS, IL-1β, and IL-6, and increasing antioxidant factors across neuronal, glial, immune, and epithelial cells. - CBG may bidirectionally influence gut microbiota composition by promoting eubiosis and symbiotic bacterial populations, which in turn modulate eCBome tone through production of neurotransmitters, cytokines, and enzymes that generate endogenous cannabinoid-mimetic compounds. - The review identifies a significant research gap: no preclinical assays currently demonstrate the specific mechanisms by which CBG modulates gut microbiota-eCBome crosstalk, whether anti-inflammatory and analgesic effects are microbiota-dependent, or how CBG directly affects microbial communities. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. The review notes CBG has no psychotropic effects, distinguishing it from other phytocannabinoids. **Evidence Quality** This is a narrative review without primary data synthesis or meta-analysis, representing lower-level evidence (Level 4). Significant limitations include: (1) the mechanistic understanding of CBG-microbiota-eCBome interactions remains theoretical and largely unexplored experimentally; (2) no human clinical trials evaluating CBG efficacy are discussed; (3) the review acknowledges absence of specific preclinical assays establishing causality between CBG administration and microbiota changes; (4) unclear whether observed effects are direct pharmacological actions of CBG or indirect through microbiota modulation. Authors conclude that translational research is needed, particularly in vivo and clinical studies specifically designed to evaluate CBG's effects on the gut microbiota-eCBome axis and to determine microbiota-dependency of therapeutic outcomes in inflammation and chronic pain conditions.

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