What Is The Precise Molecular Mechanism By Which Cannabidiol (CBD) Modulates The Activity Of Voltage-gated Sodium Channels In The Hippocampal Neurons Of Patients With Temporal Lobe Epilepsy, And How Does This Impact The Efficacy Of CBD As An Adjunctive Therapy In Reducing Seizure Frequency In This Specific Patient Population?

Cannabidiol (CBD) modulates voltage-gated sodium channels in hippocampal neurons of patients with temporal lobe epilepsy primarily through indirect mechanisms. While CBD does not directly block these channels, it influences neuronal excitability by interacting with the endocannabinoid system, particularly CB1 receptors, which reduce excitatory neurotransmitter release. Additionally, CBD may affect sodium channel gating and expression, potentially targeting specific subtypes that contribute to hyperexcitability. Its interaction with other channels, such as TRPV1, and its anti-inflammatory properties further contribute to reducing neuronal excitability. Clinical evidence, including trials with Epidiolex, supports CBD's efficacy as an adjunctive therapy in reducing seizure frequency, particularly in drug-resistant cases. Thus, CBD's multi-faceted approach decreases seizure frequency by dampening neuronal hyperexcitability through various pathways.