Comparative analysis of the effects of Δ9-tetrahydrocannabinol and cannabidiol on pilocarpine-induced status epilepticus in mice.

Gatica R.; Noches V.; González M.; Henny P.; Andrés M. · Neuroscience · 2026

**Background & Methods** This experimental study compared the acute effects of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) during pilocarpine-induced status epilepticus in male C57BL/6 mice. Seizures were induced via intraperitoneal pilocarpine injection, followed by cannabinoid administration, with assessment of behavioral seizure severity, cortical electrical activity via electrocorticography, and neuroLSD1 gene expression via real-time PCR. **Key Findings** • CBD administration did not alter seizure severity or reverse behavioral manifestations of status epilepticus, suggesting limited acute anticonvulsant efficacy in this experimental model. • THC reduced seizure severity compared to control, but this benefit was substantially limited by marked sedation in treated animals, complicating clinical interpretation of seizure reduction. • Neither CBD nor THC reversed the electroencephalographic abnormalities induced by pilocarpine, indicating that acute cannabinoid administration does not normalize cortical electrical activity during active seizures. • THC uniquely prevented seizure-induced downregulation of neuroLSD1, maintaining this transcriptional regulator at physiological baseline levels despite the epileptic insult, suggesting a potential neuroprotective mechanism distinct from direct anticonvulsant action. **Dosage & Administration** CBD: 100 mg/kg intraperitoneal injection THC: 10 mg/kg intraperitoneal injection Both administered acutely following pilocarpine 300 mg/kg intraperitoneal injection **Safety & Adverse Effects** Marked sedation was observed in mice receiving THC, representing a significant adverse effect that complicated interpretation of seizure reduction. No specific adverse effects were reported for CBD administration. **Evidence Quality** This is a preclinical animal study with moderate limitations. The use of a single rodent model and sex (males only) restricts generalizability to human populations. The acute single-dose design does not reflect chronic therapeutic cannabinoid regimens currently approved for refractory epilepsy. While the study provides mechanistic insights regarding neuroLSD1 regulation, the lack of electrocorticographic reversal and minimal behavioral benefit of acute dosing suggest that single-dose acute cannabinoid administration may be insufficient for seizure management. The findings contradict some clinical efficacy of chronic CBD therapy, highlighting the distinction between acute and chronic cannabinoid effects. This represents level 4 evidence (animal research), supporting the need for translational studies investigating chronic dosing strategies.

More recent cannabis research