Cannabidiol Attenuates Seizures and Social Deficits in a Mouse Model of Dravet Syndrome

Kaplan JS, Stella N, Catterall WA, Westenbroek RE; Proc Natl Acad Sci U S A. 2017

Purpose

• On this site, we have covered various research on the efficacy of cannabidiol (CBD) in the treatment of epilepsy, such as:
  • The use of CBD in drug-resistant epilepsy
  • The efficacy of CBD in reducing seizure frequency in children and adults with four or more seizures per month
  • Effect of Epidiolex^®, a purified CBD, in the treatment of Lennox-Gastaut syndrome
• Since these studies that have been done in people with various epilepsy syndromes, little is known about how CBD produces its effects.
• Studies in experimental animals are necessary to understand the mechanism of action (how it works) of CBD in epilepsy.
  • In the current study, researchers looked at the effects of CBD in a mouse model of Dravet syndrome.
  • Dravet syndrome is a neurological disorder characterized by refractory seizures (i.e., seizures that do not respond to medications), neuropsychiatric disturbances, and a host of other conditions.
  • Given that Dravet syndrome can be associated with premature death, it is critical that we find novel therapies for it.
  • Indeed, the usefulness of Epidiolex^® in children and young adults with Dravet syndrome has been investigated and reported.

Description of Study

• Dravet syndrome is caused by a mutation in a gene called SCN1A.
  • Scientists have developed mouse models of Dravet syndrome by targeting the SCN1A gene.
  • Mice with this specific mutation show seizure characteristics and social abnormalities that are like those seen in people with Dravet syndrome.
• In the current study, scientists used the Dravet syndrome mice and looked at the effects of CBD on seizures (such as how frequent the seizures are, how long do they last, and when they do occur) and on behavioral characteristics.
• Finally, in an attempt to understand the mechanism (how) by which CBD exerts its effects, the scientists explored the GABAergic system.
  • GABA is a neurotransmitter that is responsible for inhibiting (or dampening down) excitation.
  • Dravet syndrome is associated with abnormalities in the GABAergic system, so it makes sense to see whether CBD has an effect on this neurotransmitter.
• A combination of experimental techniques (such as seizure generation and monitoring, behavioral analyses, and electrophysiology) was used.

Summary of Study Findings

• Similar to what is seen in people with Dravet syndrome, the study’s authors saw that CBD decreases seizures in mice with Dravet syndrome.
• CBD was also able to reduce deficits in social interaction seen in mice with Dravet syndrome.
• As expected, the scientists found that CBD enhances GABAergic neurotransmission, which may explain its effects on seizure reduction and improvement in behavior.

What does this mean?

• As compared to other anti-epileptic drugs, CBD has relatively fewer side-effects.
• It is exciting to figure out how CBD produces its effects to reduce seizures, because this finding could provide the scaffold for future experiments.

Article published in Proc Natl Acad Sci U S A, October 2017.