Characterization and Anticonvulsant Effects of a Colombian Cannabis sativa Extract: A Preclinical Study in Murine Models of Epilepsy

Background: Epilepsy represents one of the most prevalent chronic neurological disorders worldwide, affecting approximately 50 million people globally. Despite the availability of numerous antiseizure medications (ASMs), approximately 30% of patients develop drug-resistant epilepsy, necessitating the exploration of novel therapeutic alternatives. Cannabis sativa has emerged as a promising source of anticonvulsant compounds, particularly cannabidiol (CBD) and Delta-9-tetrahydrocannabinol (THC), which have demonstrated antiepileptic properties in preclinical models. Methods: This study characterized a chloroform extract of Cannabis sativa cultivated in Colombia and evaluated its anticonvulsant potential in three established murine seizure models: the 6 Hz psychomotor seizure model, the pentylenetetrazol (PTZ)-induced seizure model, and the maximal electroshock seizure (MES) test. Phytochemical characterization was performed using thin-layer chromatography (TLC), colorimetric assays (Duquenois-Levine and Fast Blue B Salt), and gas chromatography coupled with mass spectrometry (GCMS/ EI) and flame ionization detection (GC-FID). Results: Chemical analysis revealed a nearly 1:1 ratio of CBD to THC (51% CBD, 49% THC) in the extract, representing an atypical chemotype. In the 6 Hz model, the extract at 100 mg/kg demonstrated complete protection against seizures, comparable to levetiracetam (40 mg/kg). In the MES test, both 50 and 100 mg/kg doses significantly reduced seizure-related mortality. However, in the PTZ model, the extract showed limited efficacy and appeared to exacerbate seizure severity at higher doses, suggesting potential proconvulsant interactions. Conclusions: This study provides evidence for the anticonvulsant potential of a Colombian Cannabis sativa extract in specific seizure models, particularly those involving generalized tonic-clonic and psychomotor seizures. The unique 1:1 CBD:THC ratio suggests possible synergistic interactions between these major cannabinoids. These findings support further investigation of cannabis-based therapies for drug-resistant epilepsy, while highlighting the importance of careful dose optimization and model-specific efficacy considerations.