Cannabidiol benefits and mechanisms shown in mouse study of Dravet syndrome

October 10, 2017, University of Washington
Ball-and-stick model of the cannabidiol molecule. Credit: Public Domain

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 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, however, 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. They found that higher doses of clonazepam were required to control Dravet syndrome seizures, but lower doses to treat its autistic and cognitive aspects.

In looking at how cannabidiol affects brain neurons in the Dravet syndrome mouse model, the researchers observed that it rebalances the ratio of excitation to inhibition in the hippocampus. This is a part of the brain involved in learning and memory.

These experimental findings suggest that cannabidiol reverses Dravet 's core deficit, which is failure of the brain's inhibitory neurons to fire electrical signals and control the activity of nearby excitatory neurons. The researchers also found that cannabidiol may act by antagonizing GPR55, a brain receptor that remains poorly understood.

Determining the detailed molecular mechanism that mediates the therapeutic actions of cannabidiol may suggest development strategies for new drugs aimed at GPR55, according to the researchers. Such potential new class of medicines would ideally be more effective against seizures and cognitive deficit and would enter the brain more efficiently than the currently available therapeutics.

Compared to many existing medications for epilepsy, cannabidiol shows fewer and milder side effects. The researchers concluded that this study contributes to the emerging data that supports the efficacy of in otherwise treatment-resistant epilepsy and may lead to improved therapies for these debilitating diseases.

Explore further: Cannabis derivative cannabidiol reduces seizures in severe epilepsy disorder

More information: Joshua S. Kaplan et al, Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1711351114

Related Stories

Cannabis derivative cannabidiol reduces seizures in severe epilepsy disorder

May 24, 2017
After years of anecdotal claims about its benefits, the cannabis derivative cannabidiol reduced seizure frequency by 39 percent for patients with Dravet syndrome - a rare, severe form of epilepsy - in the first large-scale ...

Cannabis-based medicine may cut seizures in half for those with tough-to-treat epilepsy

April 18, 2017
Taking cannabidiol may cut seizures in half for some children and adults with Lennox-Gastaut syndrome (LGS), a severe form of epilepsy, according to new information released today from a large scale controlled clinical study ...

Study shows promise for children with severe form of epilepsy

October 2, 2017
A new formulation of a drug that was used to treat children with a rare neurological condition in the 1980s, and later became half of a widely used diet-drug combination, may offer promise for pediatric patients with a severe ...

Heat a trigger for seizures

September 7, 2017
Fever is the most common trigger for seizures in children between 5 months and 6 years of age. But the underlying cause is not always clear.

Review: cannabidiol may be beneficial for oral mucositis

February 16, 2017
(HealthDay)—Cannabidiol could be beneficial for the treatment of oral mucositis, although data on its use in dentistry are scarce, according to a review published online Feb. 12 in the Journal of Clinical Pharmacy and Therapeutics.

Brazil approves marijuana derivative for medical treatment

January 14, 2015
Brazil on Wednesday for the first time approved the use of a marijuana derivative to treat people suffering from severe seizures and other conditions.

Recommended for you

Scientists discover how brain signals travel to drive language performance

June 21, 2018
Effective verbal communication depends on one's ability to retrieve and select the appropriate words to convey an intended meaning. For many, this process is instinctive, but for someone who has suffered a stroke or another ...

Scientists discover fundamental rule of brain plasticity

June 21, 2018
Our brains are famously flexible, or "plastic," because neurons can do new things by forging new or stronger connections with other neurons. But if some connections strengthen, neuroscientists have reasoned, neurons must ...

Researchers find mechanism behind choosing alcohol over healthy rewards

June 21, 2018
A new study links molecular changes in the brain to behaviours that are central in addiction, such as choosing a drug over alternative rewards. The researchers have developed a method in which rats learn to get an alcohol ...

Waking up is hard to do: Prefrontal cortex implicated in consciousness

June 21, 2018
Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers ...

Study on instinctive behaviour elucidates a synaptic mechanism for computing escape decisions

June 21, 2018
How does your brain decide what to do in a threatening situation? A new paper published in Nature describes a mechanism by which the brain classifies the level of a threat and decides when to escape.

'Antifreeze' molecules may stop and reverse damage from brain injuries

June 21, 2018
The key to better treatments for brain injuries and disease may lie in the molecules charged with preventing the clumping of specific proteins associated with cognitive decline and other neurological problems, researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.