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

Lillian Soares Pinto¹Matheus Silva de Oliveira¹Giovanna Bruno Borges¹Olagide Wagner Castro²Fabrício de Araújo Moreira¹Victor Rodrigues Santos^1*

• ¹Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil
• ²Universidade Estadual de Ciencias da Saude de Alagoas, Maceió, Brazil

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 minutes, 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.