Cannabidiol Reduces Seizures, EEG Abnormalities in AS Mice, Study Finds

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Treatment with cannabidiol reduces seizures and abnormal electric brain activity in mice with Angelman syndrome (AS), supporting its use as an anti-seizure treatment for patients, a study finds.

The study, “Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice,” was published in bioRxiv, a preprint biology platform.

AS is a genetic neurological disorder caused by the loss or malfunction of the maternal copy of the UBE3A gene in neurons from specific regions of the brain. This gene provides instructions to make an enzyme called ubiquitin protein ligase E3A, which normally targets other proteins to be destroyed.

Although the disorder can make itself known in different ways, 80–95% of patients have epilepsy, which is often resistant to treatment with standard anti-epileptic medications.

Cannabidiol (CBD) is a purified liquid formulation of plant-derived cannabis that has strong anti-seizure, anti-psychotic and anxiolytic properties.

In 2018, the U.S. Food and Drug Administration approved Epidiolex (cannabidiol) for the treatment of epileptic seizures in children with Dravet syndrome and Lennox-Gastaut syndrome, two rare forms of epilepsy that fail to respond to treatment with conventional anti-epileptic drugs.

“However, little is known about the potential anti-epileptic and other benefits of CBD in AS,” the investigators said.

In this study, a group of researchers from the University of North Carolina set out to examine the effects of CBD on abnormal electric brain activity associated with with epileptic seizures in a mouse model of AS.

The investigators used three approaches to trigger epileptic seizures in the animals: acoustic stimuli; increase in body temperature (hyperthermia stimuli); and treatment with flurothyl, a volatile compound that triggers epileptic seizures, once a day, for a period of eight days and a retest after 36 days.

They also used two CBD treatment regimens: an acute treatment regimen, in which animals were treated with CBD at a dose of 100 mg/kg one hour before receiving stimuli to induce seizures; and a two-week course of treatment with CBD at a dose of 100 mg/kg, administered once a day by intraperitoneal (through the abdominal wall) injection.

Results showed that acute treatment with CBD reduced the frequency and severity of seizures induced by acoustic and hyperthermia stimuli. However, neither the acute nor the two-week treatment with CBD prevented the enhanced seizure activity normally observed in animals during the retest period with flurothyl.

CBD also normalized animals’ brain electric activity, suggesting its use may be beneficial to correct abnormal patterns of brain activity seen by electroencephalogram (EEG) in AS patients.

Investigators also found that CBD had a mild sedative effect on the animals. However, this effect was not strong enough to compromise their ability to move normally.

“This suggests that CBD can suppress pathological EEG signatures in AS model mice, and perhaps in AS individuals [and] lends critical support for using CBD to treat seizures, along with behavioral and EEG abnormalities in AS, and expands the potential beneficial spectrum of CBD,” the researchers concluded.