Cannabidiol Pretreatment Reduces Status Epilepticus and Glutamate Uptake Induced by Kainic Acid in Adult Zebrafish

Cannabis Cannabinoid Res. 2025 May 12. doi: 10.1089/can.2024.0189. Online ahead of print.

ABSTRACT

Background: Epilepsy is a neurological chronic disorder that affects about 70 million people worldwide. Status epilepticus (SE) are neural disturbances that cause intense glutamatergic excitatory discharges that modulate changes in normal brain physiological activity. Cannabidiol (CBD) is the main nonpsychomimetic compound present in Cannabis sativa and exhibits a wide spectrum of neuroprotective properties. The use of zebrafish (Danio rerio) is regarded as an important alternative animal model for studies on seizures, as it has neuronal mechanisms similar to humans. Objective: This study aims to evaluate the effects of CBD on SE induced by kainic acid (KA) in zebrafish. Methods: Animals received CBD (5, 10, or 40 mg·L^-1 tank water) for 24 h followed by KA administration (5 mg/kg intraperitoneally). The convulsive pattern of alterations was then assessed. After 12 h, cerebral glutamate transport and oxidative stress were also verified. Results: CBD at 5 and 40 mg·L^-1 induced a significant decrease in the seizure intensity (26.1% and 29.9%) and an increase in the latency to reach SE (from 10.71 min to 17.5 and 25 min), respectively. In addition, CBD administration (40 mg·L^-1) attenuated the decrease in cerebral glutamate transport following 12 h KA-induced seizure. The KA-induced seizure was also able to alter the oxidative stress parameters 2′,7′-dichlorofluorescin, and catalase activity. However, CBD (40 mg·L^-1) did not influence these markers. The present study indicates that CBD promotes a neuroprotective response against the epileptic profile in zebrafish. These findings contribute to the understanding of the influence of CBD on the modulation of excitatory/inhibitory disruption on zebrafish seizure.

PMID:40354278 | DOI:10.1089/can.2024.0189