Cannabidiol (CBD) showed anticonvulsant action in several preclinical models and is
currently approved by regulatory agencies to treat childhood epilepsy syndromes. However,
CBD treatment has limited benefits, and its long-term effects on cognition are not
fully understood yet. This study aimed to examine the impact of long-term CBD treatment
in the pentylenetetrazole (PTZ)-kindling model of epilepsy. Adult male Wistar rats
(N = 24) received PTZ (35 mg/kg intraperitoneally) every other day until two consecutive
generalized seizures occurred. CBD (60 mg/kg body weight) was administered daily by
the oral route until the kindled state was achieved (n = 12). To confirm that the
formulation and administration techniques were not of concern, liquid chromatography–mass
spectrometry was performed to test the brain penetration of the CBD formula. As a
result of CBD treatment, a lower mortality rate and significantly prolonged generalized
seizure latency (925.3 ± 120.0 vs. 550.1 ± 69.62 s) were observed, while the frequency
and duration of generalized seizures were not influenced. The CBD-treated group showed
a significant decrease in vertical exploration in the open field test and a significant
decrease in the discrimination index in the novel object recognition (NOR) test (−0.01
± 0.17 vs. 0.57 ± 0.15, p = 0.04). The observed behavioral characteristics may be
connected to the decreased thickness of the stratum pyramidale or the decreased astrogliosis
observed in the hippocampus. In conclusion, CBD treatment did not prevent kindling,
nor did it affect seizure frequency or duration. However, it did increase the latency
to the first seizure and decreased the prolonged status epilepticus-related mortality
in PTZ-kindled rats. The cognitive impairment observed in the NOR test may be related
to the high dose used in this study, which may warrant further investigation.
