New uses for CBD in genetic brain disorder

Cannabidiol (CBD) has been much in the news for the right reasons, as it is being found to have a host of medical applications. Now a new study shows that this marijuana extract can help people with a rare brain condition called Angelman syndrome to improve behavioral traits and to control their seizures.

This syndrome is present at birth, caused by the absence or mutation of the UBE3A gene from the mother. It causes intellectual retardation, inability to speak, impaired gait and balance, irregular brain waves leading to frequent seizures, which not only harm brain function and the patient’s overall health further but often do not respond to anti-seizure drugs.

The study was published in the Journal of Clinical Investigation on September 10, 2019.
CBD is known to have anti-seizure effects, to reduce anxiety, and counter psychosis. It has received approval from the US Food and Drug Administration (FDA) as a drug for treating two infrequently encountered forms of epilepsy. However, this study deals with its use in Angelman syndrome, to reduce behavioral abnormalities and to control seizure activity.

Angelman syndrome was reproduced in mousemodels, and they were then treated with CBD in increasing doses, while observing seizure patterns and frequencies, motor problems and abnormalities in brain electrical activity on electroencephalography (EEG).

The researchers discovered that a single dose of CBD by injection significantly reduced the severity of seizures that had been triggered by causing a rise in body temperature or loud noises. At a dose of 100 mg/kg, which is usually used in epilepsy, CBD causes the mice to become a little sedated but without any other significant benefit on motor skills or memory.

However, the mice with AS are different from AS in humans, in that the former show reduced motor activity while the latter are often hyperactive. The higher the dose, the greater was the sedation produced. The impaired brain rhythms were normalized as well.

However, the administration of CBD could not produce any change in the neuroplastic changes which could then lead to the establishment of a seizure focus. Neuroplasticity refers to the way the central nervous system can respond to a variety of normal or disease-related stimuli by a change in its structure or function, which may be only for a short while or durably. This is achieved by producing both new neurons and their connections.

Neuroplastic changes constantly go on, at any stage of life, and may compensate for cerebral damage. In some cases, neuroplasticity can cause neurological development or degenerative illness, as in childhood seizures. This is called epileptogenesis, and is due to progressive reorganization of the neural network.

CBD was unable to arrest the process of neuroplasticity which led to the emergence of epileptogenic foci, whether it was given as a single dose or over two weeks just after a kindling protocol (when repeated seizures are induced to produce longer and more severe induced seizures until they reach a steady state).

This promising study serves as a foundation to build the correct dosage and use of CBD as a rational therapy for Angelman-associated seizures and also those found in other similar conditions. However, the researchers emphasize that the drug must be tested in human clinical trials, and to be taken only under medical supervision.

Journal reference:

Bin Gu, Manhua Zhu, Madison R. Glass, Marie Rougié, Viktoriya D. Nikolova, Sheryl S. Moy, Paul R. Carney, and Benjamin D. Philpot. Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice. Journal of Clinical Investigation. https://doi.org/10.1172/JCI130419. September 10, 2019