Preprint Article Version 1 This version is not peer-reviewed

Subthreshold Cannabidiol Potentiates Levetiracetam in the Kainic Acid Model of Temporal Lobe Epilepsy

Version 1 : Received: 9 August 2024 / Approved: 12 August 2024 / Online: 12 August 2024 (14:14:22 CEST)

How to cite: Lucchi, C.; Marcucci, M.; Aledresi, K. A. M. S.; Costa, A.-M.; Cannazza, G.; Biagini, A. G. Subthreshold Cannabidiol Potentiates Levetiracetam in the Kainic Acid Model of Temporal Lobe Epilepsy. Preprints 2024, 2024080813. https://doi.org/10.20944/preprints202408.0813.v1 Lucchi, C.; Marcucci, M.; Aledresi, K. A. M. S.; Costa, A.-M.; Cannazza, G.; Biagini, A. G. Subthreshold Cannabidiol Potentiates Levetiracetam in the Kainic Acid Model of Temporal Lobe Epilepsy. Preprints 2024, 2024080813. https://doi.org/10.20944/preprints202408.0813.v1

Abstract

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p<0.001, Duncan’s new multiple range test) and their total duration (p<0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p<0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

Keywords

cannabidiol; epilepsy; kainic acid; levetiracetam

Subject

Medicine and Pharmacology, Neuroscience and Neurology

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