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Canna~Fangled Abstracts

Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K

By September 16, 2022September 18th, 2022No Comments

. 2022 Sep 16.

doi: 10.1007/s43440-022-00391-y.

Online ahead of print.
Isabel Vieira de Assis Lima 1, Hyorrana Priscila Pereira Pinto 2, Paula Maria Quaglio Bellozi 1, Maria Carolina Machado da Silva 1, Luciano R Vilela 1, Fabrício A Moreira 1, Márcio Flávio Dutra Moraes 3, Antônio Carlos Pinheiro de Oliveira 4
Affiliations 

Abstract

Background: The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).

Methods: We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.

Results: PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.

Conclusion: Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.

Keywords: Cannabidiol, Cannabinoids, Epilepsy, PTZ, Phosphatidylinositol 3-kinase, Seizures

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