Cannabidiol reduces seizures following CNS infection with Theiler's murine encephalomyelitis virus

Epilepsia Open

Robert S. Fujinami¹  Glenna Wallis²  Misty D. Smith²  Karen S. Wilcox²  Dipan C. Patel² 

[1] Department of Pathology University of Utah Salt Lake City Utah;Department of Pharmacology & Toxicology University of Utah Salt Lake City Utah;

关键词: animal model;    cannabidiol;    infection;    seizures;    TMEV;   

DOI  :  10.1002/epi4.12351

来源: DOAJ

【 摘 要 】

Abstract Objective C57BL/6J mice infected with Theiler's murine encephalomyelitis virus (TMEV) develop acute behavioral seizures in the first week of infection and later develop chronic epilepsy. The TMEV model provides a useful platform to test novel antiseizure therapeutics. The present study was designed to test the efficacy of cannabidiol (CBD) in reducing acute seizures induced by viral infection. Methods C57BL/6J mice were infected intracortically with 2 × 105 plaque‐forming units of TMEV. Mice were divided into two treatment groups—1) CBD‐treated mice and 2) vehicle‐treated mice. Frequency and severity of acute seizures were evaluated by video‐monitoring the mice four times daily by the experimenter blinded to the treatment group. Results Cannabidiol (180 mg/kg; 360 mg/kg/day) decreased both the frequency and severity of acute behavioral seizures following TMEV infection, but 150 mg/kg of CBD did not improve overall seizure outcome. The time to peak effect (TPE) of CBD in the 6 Hz 32 mA psychomotor seizure test using C57BL/6J mice was observed at 2 hours post‐CBD treatment. Interestingly, CBD (150 mg/kg) significantly reduced frequency and severity of TMEV‐induced acute seizures at 2 hours post‐CBD treatment. These results suggest that CBD could be effective in decreasing TMEV‐induced acute seizures when the seizure test is conducted at the TPE of CBD. Significance Cannabinoids are increasingly studied for their potential antiseizure effects. Several preclinical and clinical studies provide evidence that CBD could be an effective therapy for intractable epilepsies. The present study corroborates those previous findings and provides an opportunity to investigate pharmacokinetics, pharmacodynamics, and mechanism(s) of antiseizure effects of CBD in the TMEV model, which may help to design future clinical studies more effectively.

【 授权许可】

Unknown