# Cannabidiol in Developmental Epilepsy: Organoid-Guided Precision Medicine Across Critical Neurodevelopmental Windows

## TL;DR

This paper explores how cannabidiol (CBD) can be used in precision medicine for developmental epilepsy by using brain organoids to guide treatment during critical brain development stages.

## Contribution

Introduces human brain organoids as a platform for studying CBD's effects on epilepsy during neurodevelopmental windows.

## Key findings

- CBD has pleiotropic antiseizure and neuroprotective effects through multiple molecular pathways.
- CBD may modify epileptogenic trajectories when administered during specific neurodevelopmental windows.
- Human brain organoids enable functional profiling of CBD-responsive phenotypes and developmental safety assessment.

## Abstract

Epilepsy is a progressive network disorder in which recurrent seizures drive maladaptive neurodevelopmental remodeling, cognitive decline, and pharmacoresistance, particularly in developmental epileptic encephalopathies. Cannabidiol (CBD) has emerged as an evidence-based adjunctive therapy for selected childhood-onset epilepsies; however, its broader clinical utility remains limited by heterogeneous responsiveness, restricted indications, and an incomplete understanding of developmental stage–specific efficacy and safety. Here, we synthesize molecular, preclinical and clinical evidence supporting the pleiotropic antiseizure and neuroprotective actions of CBD, including modulation of endocannabinoid-related G protein–coupled receptors, adenosine signaling, transient receptor potential channels, GABAergic maturation, and neuroinflammatory cascades. We highlight critical neurodevelopmental windows during which timely CBD intervention may exert disease-modifying effects by preventing pathological consolidation of hyperexcitable networks. Furthermore, we position human brain organoids as transformative translational platforms that recapitulate early human cortical development and epileptic network dynamics, enabling functional stratification of CBD-responsive phenotypes, developmental safety profiling, and precision therapeutic discovery within human-relevant neural circuits. Collectively, organoid-guided frameworks provide a mechanistic foundation for personalized, developmentally informed CBD therapy and advance precision medicine strategies aimed at modifying epileptogenic trajectories rather than solely suppressing seizures.