Cannabidivarin Safe, Reduces Seizures in Five Rett Patients: Study

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Cannabidivarin (CBDV) treatment was well tolerated and reduced the monthly frequency of seizures in five children with Rett syndrome, according to data from a Phase 1 trial.

“In our small patient cohort [group] of children with drug resistant epilepsy and MECP2-related RTT [Rett syndrome], CBDV treatment was well tolerated and an overall trend toward reduction in mean monthly seizure frequency was observed,” the researchers wrote, adding that the data overall support additional trials of the therapy in children with Rett or other seizure disorders.

The study, “The efficacy and safety of cannabidivarin treatment on epilepsy in girls with Rett syndrome: A phase I clinical trial,” was published in Epilepsia

Rett syndrome is usually caused by mutations in the MECP2 gene, which severely affects brain function. Epilepsy is a common symptom, reported in up to 90% of Rett patients. For many, currently available anti-seizure medications are ineffective.

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Phytocannabinoids are a class of chemical substances derived from the cannabis plant, which may cross the selective blood-brain barrier and affect brain function. For this reason, they have emerged as promising treatment candidates for several neurological diseases, including epilepsy.

Preclinical studies in mice and rats suggest that CBDV — a phytocannabinoid that does not change the perception of reality — has anti-seizure effects, and when tested in adults with epilepsy, the treatment showed an ability to reduce seizure frequency.

While CBDV was shown to improve sociability and brain weight, delayed the appearance of motor deficits and rescued memory defects in a mouse model of Rett, its effects in Rett patients — particularly on seizures — has not been explored.

The Phase 1 trial aimed to determine CBDV’s safety, tolerability, and anti-epileptic effects in five girls with Rett (median age, 12.6) at a children’s hospital in Australia. All had epilepsy that had failed to respond to at least two other standard anti-epileptic medications.

Patients began CBDV treatment at 2.5 mg/kg twice per day. If no side effects were reported, the dose was increased by an additional 2.5 mg/kg every week up to a maximum dose of 10 mg/kg per day.

The final mean dose was 9.9 mg/kg daily. Three patients had their dose lowered for brief periods due to side effects, but it was later increased in all cases.

Overall, 77 side effects were reported, the most common being infections (22.1%), neurological effects (20.8%), general (14.3%), and skin (13%) disorders. Most side effects were considered mild (77.9%) and 23 of them — including excessive sleepiness, drooling and diarrhea — were expected, the researchers said.

Among all 77 side effects, three could be definitively associated with CBDV — two cases of excessive sleepiness and one episode of drooling — with an additional 24 (31.2%) considered possibly related to treatment.

Of the 16 side effects that were considered serious, none were definitively related to CBDV treatment. While five were thought to be possibly related, a link to CBDV treatment was later determined to be “unlikely,” the researchers said. All of these five events — tremor, forward lean, hand contortion, and two cases of body trunk tilt — were observed in a single patient.

At the study’s start, or baseline, the mean seizure frequency was 32 a month, which declined by 82% after the treatment’s start to 6.3 per month. All five patients reported a reduced seizure burden, with three showing a greater than 75% reduction in seizure frequency. Four were able to reduce the use of their other anti-seizure medications after starting CBDV.

Electroencephalograms were used to record patients’ electrical brain activity before and after treatment. Results were consistent with what is known in Rett, the team said, but the small sample size precluded measurement of CBDV’s effects.

Other Rett symptoms were measured with the Rett Syndrome Behavioral Questionnaire (RSBQ). Baseline and post-treatment data were available for three girls — two of whom experienced mild behavioral improvements in symptoms such as mental alertness, attention, and eye contact, while a 20% increase in symptoms was observed in the other patient.

Despite the small number of patients and lack of a control group — which limited the findings — the results “are promising regarding the use and safety of CBDV in children with RTT-related epilepsy,” the researchers wrote.

“This extends current data to confirm tolerability in a paediatric population and support trials investigating the use of CBDV in other neurodevelopmental conditions associated with drug-resistant epilepsy. A larger Phase II trial would be required to test the validity of these results,” the team concluded.