New Research Reveals Why CBD Is Such An Effective Treatment For Seizure Disorders
The novel findings give us insight into other common conditions as well.
Long before CBD was a household name, parents of kids with epilepsy were engaging in a whisper network: a non-psychoactive compound found in cannabis and hemp, they said, had helped reduce or eliminate their children’s seizures.
Cannabis’ Schedule 1 classification, combined with the fact that they were giving a treatment not approved by the FDA to their children, meant parents faced terrifying consequences for getting caught doing so. Nevertheless, a handful of brave parents came forward to publicly talk about the success they’d had treating their kids’ epilepsy with CBD, and a public push to develop and test a CBD-based epilepsy drug slowly but steadily grew. In 2018, the FDA approved one such medication, Epidiolex.
The clinical data was unequivocal: The CBD-based medication could treat many seizure disorders with very few, if any, side effects. Exactly why CBD was so effective, however, has remained fairly unclear. But a study published last week in the journal Neuron may offer some answers. The researchers’ findings provide a window into the neurobiology of epilepsy and suggest exciting implications for future treatments.
How CBD treats epilepsy and what that tells us about seizure disorders
Richard Tsien, chair of the department of physiology and neuroscience at NYU Langone Health and one of the researchers on the study, tells Inverse that understanding the mechanism by which CBD works may help us understand how seizure disorders happen.
Our neural networks are teeming with electrical activity all the time. Electrical signals are sent along a neuronal path until they reach a gap. At the gap, neurotransmitters are released, signaling the next neuron. That signaling can either be excitatory or inhibitory. When it’s excitatory, it activates an action in the receiving neuron. When it’s inhibitory, the activity is inhibited or prevented in the receiving neuron. The appropriate ratio of excitatory to inhibitory actions allows our brains to function optimally — there’s neither too much excitatory signaling nor too much inhibitory signaling happening at one time.
The neurotransmitters in question here are GABA and Glutamate, and a specific type of glutamate receptor called G-protein-coupled receptor 55 (GPR-55). When glutamate binds with GPR-55, it lets sodium ions through the membrane and causes the neuron to become depolarized. “GABA tries to oppose that depolarization,” Tsien says.
Another key player in regulating the ratio of excitatory to inhibitory signaling is a molecule called lysophosphatidylinositol (LPI).
“LPI is the body's own way of regulating the strength of excitatory glutamatergic transmission, and inhibitory, GABAergic transmission in the watchdog, to make sure that excitation is brisk, and inhibition is held in check,” Tsien says. “That's because neural circuits thrive up to a point in having enough excitability to process information. And someone's got to spy on how strong the excitation is and how weak the inhibition is.”
Under normal circumstances, LPI functions a bit like a hall monitor; it’s trying to get as many students down the hall and into their classrooms as quickly and efficiently as possible. If you have too much LPI, however, the hall monitor becomes more akin to a fire alarm, amplifying too much excitation.
Tsien and his colleagues confirmed earlier studies showing that CBD blocks the ability of LPI to amplify nerve signals in the hippocampus. His team showed for the first time that LPI also weakens inhibitory signals that counter seizures, making CBD’s LPI-blocking a two-pronged treatment for a two-pronged disorder.
Additionally, CBD “has the blessing that it brings [neural activity] back from living close to the edge and dampens it while not preventing normal information processing,” Tsien says.
How a new understanding of epilepsy could help us treat other disorders
Dysregulation between excitatory and inhibitory signaling is far from an epilepsy-specific idea. Though not fully proven, a few other disorders may be rooted in this imbalance as well, says Tsien, including schizophrenia, Alzheimer’s, and autism, though much more research is needed before any preliminary conclusions can be made.
Instead of too much excitatory signaling, a disease like Alzheimer’s could involve too much inhibitory signaling, which may “contribute to the physiological effects,” Tsien says.
Because we’re still learning about the mechanisms by which our body regulates excitatory and inhibitory signaling, understanding how to correct this dysregulation could result in countless medical advances. For example, Tsien says, a molecule similar to LPI called LPA decreases excitation and inhibition (as opposed to LPI, which turns up excitation and down inhibition). “The combination of LPI and LPA could allow you to regulate synapses to whatever strength you wanted because you can play off LPI and LPA’s effects. All that autoregulation is fascinating to me,” Tsien says. “I believe it will ultimately lead to a better understanding of these diseases as well as healthy brain functioning.”