Cannabidiol Anticonvulsant Effect Is Mediated by the PI3Kγ Pathway

Neuropharmacology“The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mechanistic target of rapamycin (mTOR) signaling pathway has been associated with several pathologies in the central nervous system (CNS), including epilepsy. There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the powerful anticonvulsant properties associated with the cannabinoidergic system.

This work aims to investigate if the anticonvulsant and neuroprotective effects of cannabidiol (CBD) are mediated by PI3Kγ.

CDB increased latency and reduced the severity of pilocarpine-induced behavioral seizures, as well as prevented postictal changes, such as neurodegeneration, microgliosis and astrocytosis, in WT animals, but not in PI3Kγ-/-. CBD in vivo effects were abolished by pharmacological inhibition of cannabinoid receptor or mTOR. In vitro, PI3Kγ inhibition or deficiency also changed CBD protection observed in glutamate-induced cell death assay. Thus, we suggest that the modulation of PI3K/mTOR signaling pathway is involved in the anticonvulsant and neuroprotective effects of CBD.

These findings are important not only for the elucidation of the mechanisms of action of CBD, which are currently poorly understood, but also to allow the prediction of therapeutic and side effects, ensuring efficacy and safety in the treatment of patients with epilepsy.”

https://pubmed.ncbi.nlm.nih.gov/32574650/

“CBD is anticonvulsant in a model of pilocarpine-induced behavioral seizures. CB1 receptor mediates the effects of CBD. PI3Kγ pathway mediates the anticonvulsant neuroprotective effects of CBD.”

https://www.sciencedirect.com/science/article/abs/pii/S0028390820302240?via%3Dihub

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