Summary
Objective
Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (
CBD
) in a battery of acute seizure models. Additionally, we defined the disease‐modifying potential of chronic oral administration of
CBD
on associated comorbidities in the reduced intensity status epilepticus–spontaneous recurrent seizures (
RISE
‐
SRS
) model of temporal lobe epilepsy (
TLE
).
Methods
We evaluated the acute antiseizure effect of
CBD
in the maximal electroshock seizure, 6‐Hz psychomotor seizure, and pentylenetetrazol acute seizure tests, as well as the corneal kindling model of chronic seizures in mice following intraperitoneal administration. Median effective or behavioral toxic dose was determined in both mice and rats. Next, we tested an intravenous preparation of
CBD
(10 mg/kg single dose) in a rat model of pilocarpine‐induced status epilepticus. We defined the effect of chronic
CBD
administration (200 mg/kg orally) on spontaneous seizures, motor control, gait, and memory function in the rat
RISE
‐
SRS
model of
TLE
.
Results
CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine‐induced status epilepticus rat model,
CBD
attenuated maximum seizure severity following intravenous administration, further demonstrating
CBD
's acute antiseizure efficacy in this rat model. We established that oral
CBD
attenuated the time‐dependent increase in seizure burden and improved
TLE
‐associated motor comorbidities of epileptic rats in the
RISE
‐
SRS
model without affecting gait. Chronic administration of
CBD
after the onset of
SRS
ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task.
Significance
The present study illustrates that
CBD
is a well‐tolerated and effective antiseizure agent and illustrates a potential disease‐modifying effect of
CBD
on reducing both seizure burden and associated comorbidities well after the onset of symptomatic seizures in a model of
TLE
.