# Cannabidiol potentiates phenobarbital effects in the control of pentylenetetrazole (PTZ)-induced epileptic seizures in neonate rats

## TL;DR

The study shows that cannabidiol (CBD) can enhance the seizure-controlling effects of phenobarbital in neonate rats, suggesting CBD could be a helpful addition to current treatments.

## Contribution

The novel finding is that CBD potentiates the antiseizure effects of phenobarbital in a neonatal rat model, particularly at lower drug doses.

## Key findings

- CBD at 30, 100, or 200 mg/kg significantly enhanced the antiseizure effects of a subeffective dose of phenobarbital (10 mg/kg).
- Higher doses of CBD (100 and 200 mg/kg) modestly reduced PTZ-induced seizures when administered alone.
- CBD potentiation of phenobarbital was dose-dependent and suggests potential as an adjunct therapy for neonatal seizures.

## Abstract

Epilepsy is characterized by the predisposition to epileptic seizures resulting from neuronal hyperexcitability and hypersynchrony. Seizure management consists primarily of the long-term use of antiseizure drugs, such as phenobarbital (PB). However, many patients, especially neonates, exhibit resistance to PB and can suffer adverse effects, including abnormal neuronal apoptosis. Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid CBD has demonstrated efficacy in attenuating epileptic seizures. However, its interaction with PB remains largely unexplored. This study investigated the potentiation effect of CBD on PB in a neonatal pentylenetetrazole (PTZ)-induced seizure model. Ten-day-old (P10) Wistar rats were intraperitoneally pretreated with PB (3, 10, 30, 50, or 75 mg/kg) and/or CBD (3, 30, 100, or 200 mg/kg). After 60 min, seizures were induced by subcutaneous administration of PTZ (100 mg/kg), and seizure latency, duration, and severity were subsequently assessed. Low doses of CBD (3 and 30 mg/kg) exhibited limited efficacy when administered alone, while higher doses (100 and 200 mg/kg) modestly attenuated PTZ-induced seizures. However, CBD (30, 100, or 200 mg/kg) significantly enhanced the efficacy of a subeffective dose of PB (10 mg/kg). These results indicate a dose-dependent potentiation by CBD of PB effects, supporting the potential of CBD as an adjunct therapy for neonatal seizures.