Is this how CBD stops epileptic seizures? New study
A study reveals a previously unknown way in which cannabidiol (CBD), a substance found in cannabis, reduces seizures in treatment-resistant forms of pediatric epilepsy.
Led by researchers at NYU Grossman School of Medicine, the new study found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI). Found in brain cells called neurons, LPI is thought to amplify nerve signals as part of normal function, but can be hijacked by disease to promote seizures.
Published online February 13 in the journal Neuron, the work confirmed a previous finding that CBD blocks the ability of LPI to amplify nerve signals in a brain region called the hippocampus. The current findings argue for the first time that LPI also weakens signals that counter seizures, further explaining the value of CBD treatment.
“Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches,” said corresponding author Richard W. Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health.
“The study also clarified, not just how CBD counters seizures, but more broadly how circuits are balanced in the brain,” added Tsien. “Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact.”
Disease-Causing Loop
The research team found that either genetically engineering mice to lack GPR55, or treating mice with plant-derived CBD before seizure-inducing stimuli, blocked LPI-mediated effects on both excitatory and inhibitory synaptic transmission.
While prior studies had implicated GPR55 as a seizure-reducing target of CBD, the current work provided a more detailed, proposed mechanism of action. The authors propose that CBD blocks a “positive feedback loop” in which seizures increase LPI–GPR55 signaling, which likely encourages more seizures, which in turn increases levels of both LPI and GPR55.
Other experiments confirmed that LPI influences nerve signals by binding to a protein called G-coupled receptor 55 (GPR55) on neuron cell surfaces. This LPI–GPR55 presynaptic interaction was found to cause the release of calcium ions within the cell, which encouraged cells to release glutamate, the main excitatory neurotransmitter.
