Dravet Syndrome Mice Study Shows Cannabidiol Benefits and Action

Article by Leila Gray, UW Medicine

Dravet syndrome mice study shows cannabidiol benefits and action Cannabidiol treatment of mice with this genetic condition reduces epileptic seizures and autism-like behaviors. MEDIA CONTACT: Leila Gray

Treatment with cannabidiol reduces some major symptoms in mice with a genetic condition recapitulating Dravet syndrome, a devastating childhood brain disorder.   Cannabidiol is a non-intoxicating substance among the several active compounds derived from Cannabis plants. This molecule can also be produced synthetically.

The results of its use to treat Dravet syndrome are reported in the latest edition of the Proceedings of the National Academy of Sciences, PNAS.

Children with this syndrome have severe, difficult-to-control epilepsy.  Their seizures, which can be frequent and prolonged, first appear in infancy.  As the affected individual grows, intellectual impairments, autism-like behaviors and other debilitating problems can emerge. Many patients need nearly constant care. Some are at risk for early death. Few therapeutic options exist for this life-long condition.

UW Medicine researcher William Catterall, one of the authors of the PNAS paper, noted, “There has been increasing interest in the lay press about parents who have used cannabidiol to successfully treat their children.” Catterall is a professor of pharmacology at the University of Washington School of Medicine in Seattle.

Medicinal cannabis use is booming for many disorders, the authors of the paper said, even without enough preclinical evidence or sufficient insights into its mechanism of action.  The success of small-scale clinical trials for Dravet syndrome patients in reducing the frequency of their seizures, they explained, encourages additional research to determine if cannabidiol might help with other aspects of their condition.

“We have developed a mouse genetic model of Dravet syndrome, which is allowing us to probe more deeply into the possible beneficial effects of cannabidiol,” Catterall said.  The researchers also wanted to see how the beneficial effects of cannabidiol may depend on changes in the molecular signaling processes that certain brain neurons use to communicate with each other.

The researchers found that, in mice, cannabidiol treatment effectively reduced the severity and duration of seizures, as well as their frequency.  The Dravet mice on low-dose cannabidiol treatment spent more time interacting with mice that were strangers to them, and were less likely to try to escape these social interactions.  These results predict that Dravet syndrome patients may have better social interactions and fewer autism-like symptoms when treated with low doses of cannabidiol. This improvement in social interactions was lost at the higher doses necessary to protect against seizures.

“These findings present a conundrum for designing Dravet syndrome treatments that both control seizures and improve social behavior,” noted Nephi Stella, another researcher on the study from the UW departments of pharmacology and psychiatry and behavioral sciences.  The discrepancy is similar to that seen in an earlier study of clonazepam by Catterall and colleagues, which required higher doses to control Dravet syndrome seizures, but lower doses to treat its autistic and cognitive aspects.  Stella heads a Laboratory of Cannabis and Cannabionoid Pharmacology at UW Medicine.

Read full article here.

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