Authors :
Presenting Author: Monserrat Fuentes-Mejia, MSc – Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV)
Sandra Adela Orozco-Suárez, PhD – Unit for Medical Research in Neurological Diseases, National Medical Center; Luisa Rocha, PhD – Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV)
Rationale:
Drug resistance affects 30% of patients with epilepsy. Cannabidiol (CBD) decreases the expression of drug-resistant severe seizures in specific syndromes. At present, it is unknown if CBD prevents the development of drug-resistant epilepsy. This study was designed to investigate if the repetitive administration of CBD alone or in combination with diazepam (DZP) prevents the development of drug resistant seizures.
Methods:
Male Wistar rats (250-300 g) were used. Drug-resistant seizures were induced with the repetitive administration of 3-mercaptopropionic acid (MP) (30 mg/kg i.p. every 12 hours for 10 trials). The animals received one of the following treatments before MP administration: a) CBD+DZP treatment (n=10): CBD (200 mg/kg p.o.) and DZP (0.7 mg/kg i.m.); b) DZP treatment (n=10): DZP alone was administered alone; c) CBD treatment (n=10): CBD was applied alone; d) VHE treatment (n=10): coconut oil (9.52 ml/kg p.o.) was administered. The severity of seizures per animal was estimated with the ratio between the number of severe seizures and total amount of MP received during the experimental procedure. The establishment of drug resistance to DZP was investigated after the repetitive administration of the different treatments.
Results:
The VHE+MP and CBD+MP treatments resulted in similar ratios of severe seizures (0.019±0.0023 and 0.0207±0.0022, respectively, p=0.9127). Rats receiving DZP+MP and CBD+DZP+MP treatments showed lower ratios (0.0121±0.0022, p=0.0054 and 0.0098±0.0023, p=0.0004 respectively, vs VHE+MP). VHE+MP treatment resulted in drug-resistant seizures to DZP in 90% of the animals. CBD+MP and DZP+MP treatments caused resistance to DZP in 50% of the rats (p=0.1409 vs VHE+MP in both). CBD+DZP+MP treatment resulted in lower resistance to DZP (33%, p=0.0198 vs VHE+MP).
Conclusions:
Our results indicate that the development of drug-resistant seizures is reduced with the repetitive administration of CBD combined with DZP, an effect not evident when these drugs are applied alone. Further combinations of CBD with antiseizure medications should be investigated.
Funding:
Thanks to CONAHCyT grant A3-S-26782, scholarship 1009939 and HempMeds Mexico SA de CV.