Epidiolex Lowered Premature Mortality in Dravet Mice, Studies Find

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Epidiolex studies

Epidiolex, the first plant-derived cannabidiol (CBD) medication to be approved by the U.S. Food and Drug Administration (FDA), can reduce premature mortality and alleviate several behavioral deficits in mouse models of Dravet syndrome, according to data from two studies.

The results, “Cannabidiol improves survival and behavioural co-morbidities of Dravet syndrome in mice,” were published in the British Journal of Pharmacology.

Dravet syndrome is a severe type of drug-resistant epilepsy that causes  seizures, cognitive deficits, and increases mortality. The disorder is caused by genetic mutations in the SCN1A gene, which provides instructions for a subunit of a sodium channel that is essential for the generation and transmission of electrical signals in the brain.

Epidiolex, marketed by Greenwich Biosciences (a subsidiary company of GW Pharmaceuticals), has shown effectiveness in previous trials at lowering the frequency of seizures when used as an add-on therapy in children with Dravet and Lennox-Gastaut syndromes.

“However, little is known about its potential effect on the premature mortality and comorbidities associated with Dravet syndrome,” researchers wrote.

Now, researchers at the University of Reading in the U.K., in collaboration with investigators at GW Pharmaceuticals, showed that Epidiolex can lower mortality, anxiety, depression, and ameliorate social behavior and memory in a mouse model of Dravet.

“This is the first comprehensive longer term study in mice looking at CBD on problems associated with Dravet syndrome beyond seizure. It is the first to demonstrate that CBD treatments may have a beneficial impact [on] the problems and potentially help [reduce] early death in mice for the rare forms of epilepsy,” Alister McNeish, an associate professor in cardiovascular pharmacology at the University of Reading, and senior author of the paper, said in a press release.

In the paper, researchers reported the findings of two studies, each assessing the effects of Epidiolex in two different mouse models of Dravet.

In the first study, they explored the effects of Epidiolex in four groups of newborn mice: two that had been genetically-engineered to carry two mutated copies of the Scn1a gene (the mouse equivalent to the human SCN1A gene); and two groups of healthy animals (controls).

Mice who lack the Scn1a gene “differ from human Dravet syndrome by their complete loss of expression of NaV1.1 [sodium] channels, but they reproduce the ataxia, seizures and premature mortality commonly observed in Dravet syndrome patients,” the researchers wrote.

All animals were assigned randomly to receive either Epidiolex or a vehicle solution (control treatment), twice-a-day, via under-the-skin (subcutaneous) injections. Treatment was started when animals were eight days old and lasted until they were 25 days old or died, whichever occurred first.

They found that Epidiolex prolonged the median survival of newborn mice lacking both copies of Scn1a from 15.5 days to 16.25 days. Treatment with Epidiolex also improved the welfare rates of these animals compared to the control treatment. No adverse reactions to treatment were found in either group.

In the second study, researchers evaluated the effects of Epidiolex in three groups of mice: two groups of genetically-engineered animals that carried one mutated copy of the Scn1a gene, and one group of healthy animals.

These animals carrying the mutated Scn1a gene “recapitulate several features of Dravet syndrome including seizures, premature mortality and co‐morbidities such as social deficit, anxiety and memory impairments,” the researchers wrote.

As in the first study, animals were treated with either Epidiolex, or a vehicle solution, twice-a-day, both administered through subcutaneous injections. Treatment also was started when animals were eight days old, but in this study it lasted until they reached 52 days old, or died, whichever occurred first.

In this study, they found that Epidiolex reduced premature mortality in sick animals. Approximately 66% of Dravet mice who received placebo died before the completion of the study, in contrast to only 17% of those treated with Epidiolex.

Treatment also improved animals’ social behavior, cognitive function, and lessened signs of anxiety and depression. Moreover, it did not have any adverse effect on animals’ gait or motor function.

“These are encouraging findings for considering any development of drugs using purified botanical CBD. The development of new drugs using cannabis-derived compounds is an exciting new area of research and we hope to understand other potential benefits of CBD-derived treatments,” said Claire Williams, professor in the department of psychology at the University of Reading, and co-author of the study.

Investigators also noted study findings apply only to Epidiolex and “cannot be directly extrapolated to other CBD formulations” at this time.

Nevertheless, they are convinced “the results obtained from the present indicate that CBD may produce improvements in Dravet syndrome therapy related to survival and comorbidities in addition to seizure control.”

The study was funded by GW Pharmaceuticals, and two of its authors are employees of the company.