“Drug-resistant epilepsy (DRE) affects approximately 30% of individuals with epilepsy and remains a major clinical challenge despite the availability of multiple antiseizure medications (ASMs). Beyond recurrent seizures, accumulating evidence implicates chronic neuroinflammation, blood-brain barrier (BBB) dysfunction, excitotoxic injury, and progressive neurodegeneration as processes associated with epileptogenesis and disease progression.

While cannabidiol (CBD) has demonstrated clinical efficacy in specific DRE syndromes, increasing recognition of these mechanisms has motivated interest in exploratory, mechanism-oriented approaches that extend beyond direct seizure suppression.

Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with a pleiotropic pharmacological profile, interacting with cannabinoid receptors, transient receptor potential (TRP) channels, nuclear receptors such as peroxisome proliferator-activated receptor gamma (PPARγ), and additional neuromodulatory targets.

Preclinical studies indicate that CBG can modulate inflammatory, oxidative, and cell-survival pathways across diverse experimental models of neuroinflammatory and neurodegenerative injury. Importantly, most available evidence derives from non-epilepsy paradigms or in vitro systems, and direct support for antiseizure efficacy or disease modification in epilepsy remains limited.

This review synthesizes current preclinical evidence on the molecular targets and mechanistic actions of CBG, with particular emphasis on neuroimmune modulation and neuronal vulnerability, while critically addressing the limitations and translational gaps of the existing literature. Rather than providing confirmatory evidence, this work is intended as a hypothesis-generating framework to inform future epilepsy-focused studies evaluating whether modulation of neuroinflammatory and neurodegenerative pathways by CBG may hold relevance within disease-modifying research strategies for DRE.”

https://pubmed.ncbi.nlm.nih.gov/41919226

“Recent preclinical research has highlighted CBG as a multi-target phytocannabinoid capable of modulating neuroinflammatory, oxidative, and cell-survival pathways across diverse experimental systems.”

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1755956/full