Cannabidivarin safe, reduces seizure frequency in paediatric MECP2-related Rett syndrome

Treatment with a nonhallucinogenic phytocannabinoid, cannabidivarin (CBVD), is well tolerated in children with Rett syndrome (RTT), according to data from a phase 1 trial. Moreover, it improves seizure control in those whose disease is caused by methyl-CpG-binding protein 2 (MECP2) pathogenic variants.

The trial included five female RTT patients (median age 12.6 years) with drug-resistant epilepsy and a pathogenic MECP2 variant. All these girls received an CBDV oral solution at 50 mg/ml initially and titrated to 10 mg/kg/day.

Researchers collected data including pharmacokinetics, seizure type and frequency, adverse events, electroencephalogram (EEG), and responses to the Rett Syndrome Behaviour Questionnaire and Rett Syndrome Symptom Severity Index.

All five children achieved the maximum CBDV dose of 10 mg/kg/day. Over an average treatment period of 14.55 months, mean monthly seizure frequency decreased by about 79 percent. Of note, three children achieved a reduction of >75 percent. Overall, seizure frequency dropped from 32 to 7.2 seizures per month.

In terms of safety, most (91 percent) adverse events (AEs) were mild or moderate, and none led to treatment discontinuation. Sixty-two percent of AEs were deemed unrelated to CBDV, while 31 percent were identified as possibly related, of which nearly all were mild, and the remainder were assessed as RTT symptoms. CBDV-related AEs included hypersomnolence and drooling. None of the serious adverse events reported were related to CBDV.

There were no significant changes seen in EEG or nonepilepsy-related symptoms of RTT.