Subchronic Cannabidiol (CBD) Treatment During the Silent Period Fails to Prevent Increased Seizure Susceptibility Following Lithium-Pilocarpine-Induced Status Epilepticus

Abstract

[EN] Introduction. In recent years, cannabidiol (CBD) has been used as an adjunct therapy to anti-seizure medications for the control of seizures in patients with drug-resistant epilepsy. In addition to its anticonvulsant effect, CBD also has well-defined anti-inflammatory properties. Since neuroinflammation can trigger various pro-epileptogenic mechanisms, CBD could play an inhibitory role in this process. Epileptogenesis is the process by which epilepsy becomes a chronic disease following a brain injury, and one of its main characteristics is an increased susceptibility to seizures due to a reduced seizure threshold. However, the role of CBD in modulating this susceptibility remains poorly understood. Methodology. We developed an experimental protocol to discretely measure the seizure threshold (DMST) 7 or 14 days after lithium-pilocarpine-induced status epilepticus (SE) through the administration of small intraperitoneal (i.p.) doses of pentylenetetrazol (15 mg/kg/every 10 min). Results. Using the DMST, we observed a significant decrease in the seizure threshold after SE associated with a hypersensitivity state characterized by irritability and marked weight loss. A separate cohort of rats was treated with CBD (20 mg/kg) for 14 days following SE. Conclusions. Treatment with CBD did not improve the seizure threshold; moreover, it worsened the hypersensitivity state and delayed recovery following SE. Our results suggest that orally administered CBD, at a human-equivalent therapeutic and safe dose, does not improve susceptibility to seizure development after SE.