Over the past two decades, the use of cannabidiol (CBD) to treat epileptic seizures has gained momentum, especially when antiseizure drugs have failed.CBD’s anticonvulsant properties are well known. But new research highlights a previously unknown way CBD can reduce seizures, especially in people with treatment-resistant epilepsy.
In very basic physiological terms, an electrical impulse travels down a neuronal pathway until it reaches a gap or synapse. Here neurotransmitters are released to cross the gap and stimulate or inhibit the next cell.
Proper functioning of neural circuits requires coordination between synaptic excitation and inhibition. Dysfunction of the excitatory inhibition (E:I) ratio can lead to seizures. G protein-coupled receptor 55 (GPR55) on the surface of neurons is known to regulate the E:I ratio, but the exact mechanism is not well understood.
Similarly, it is not well understood how CBD, the non-euphoric component of cannabis, suppresses seizure activity at the molecular level. CBD is thought to act as an antagonist, blocking the effects of the naturally occurring GPR55 agonist lipid lysophosphatidylinositol (LPI).
A previous double-blind, placebo-controlled Phase III clinical trial conducted in the United States demonstrated that CBD reduced spontaneous recurrent seizures and modulated the E:I ratio of acute seizures. The efficacy of these trials led the FDA to approve his purified plant-based CBD for the treatment of seizure disorders.
A study led by researchers at the NYU Grossman School of Medicine used rodents to test the relationship between LPI and GPR55 as potential modulators of the E:I ratio and the effects of CBD on both. .
Researchers have confirmed previous findings that CBD blocks the ability of LPI to amplify neural signals in the hippocampus, a region of the brain associated with epilepsy.
However, they also discovered something previously unknown: when LPI interacts with GPR55, it dampens seizure-inhibiting signals. It means that it can bring This causes seizures to increase LPI-GPR55 signaling, causing more seizures and increasing levels of LPI-GPR55. This process continues in a vicious cycle, and he offers one explanation for prolonged seizure activity.
Our findings suggest that CBD effectively short-circuits this feedback loop and restores the E:I ratio, thereby further enhancing CBD’s value as an anticonvulsant treatment.
“Our results add to the field’s understanding of central seizure-triggering mechanisms and have many implications for the pursuit of new therapeutics,” said NYU Langone Health’s director of the Department of Physiology and Neuroscience. said Richard Tsien, corresponding author of the study.
Given that E:I imbalance is found in other conditions, the findings of this study have the potential for wider application.
“This study reveals more broadly not only how CBD counteracts seizures, but also how circuits in the brain are balanced.” Because of its existence, this paper may have a broader impact.”
A new study was published in neuron.
Source: NYU Langone Health by EurekAlert!
