Cannabidiol effects in a pharmacoresistant seizure model

BARRIONUEVO, EM.; SBARAGLINI, ML.; GOICOECHEA, S.; AUZMENDI, J.; LAZAROWSKY, A.; RUIZ, ME.; TALEVI, A.

Medellín

Congreso; XI- Congreso Latinoamericano de Epilepsia; 2021

ILAE-IBE

(Resumen aceptado para ser publicado en el congreso. Congreso con fecha original mayo 2020, postergado por la pandemia COVID-19 para febrero del año 2021. Modalidad virtual). Although there are new therapeutic alternatives for the treatment of epilepsy, about 30% of the patients with epilepsy do not respond to clinically established anticonvulsants. In the last few years, the interest on studying and understanding the effects of cannabidiol (CBD) in the CNS has reborn; recent clinical trials have demonstrated its efficiency as complementary therapy on epileptic syndromes as Dravet and Lennox-Gastaut [1, 2]. In this work we determined the anticonvulsive activity of CBD on a pharmacoresistant murine model, associated to the over-expression of the P glycoprotein, developed in our laboratory [3, 4]. Briefly, this model consists in inducing daily generalized seizures for 23 consecutive days by administration of 3-mercaptopropionic acid. As a result, all the animals become resistant to phenytoin (this resistance is associated with the overexpression of P-glycoprotein). To evaluate the severity of the crisis we used the modified Racine scale (Score 1 to 7, being 7 the most severe) [3]. On the 24th day animals were divided in 4 groups: control (vehicle), CBD (20mg/kg), CBD (20mg/kg) + PHT (18mg/kg), PHT (18mg/kg). We didn?t find significative differences on the average score of the different groups (Kruskal-Wallis, p>0.05). Nor we found significative differences on the latency times of fase 2 and fase 5 (ANOVA, p>0.05). In conclusion, cannabidiol didn?t show anticonvulsive activity in the 3-mercaptopropionic acid mice model. [1]Devinsky O et al. Epilepsia. 2019, 60(2):294-302. [2]Lattanzi S et al. Drugs Today (Barc). 2019, 55(3):177-196. [3]Enrique A. et al. Epilepsy Res. 2017 Jan;129:8-16. [4]Enrique A. et al. Epilepsy Behav. 2019 Aug 13:106451