Researchers at Aston University have contributed to the discovery of a previously unknown way in which cannabidiol (CBD), a non-psychoactive component of cannabis, can reduce seizures in many treatment-resistant forms of childhood epilepsy.
A group of international collaborators, led by scientists at NYU Grossman School of Medicine, including a team from the Aston Institute of Health and Neurodevelopment at Aston University, found that CBD blocked signals carried by a molecule called lysophosphatidylinositol (LPI).
LPI is found in our brain’s neurons and is thought to amplify nerve signals as part of normal function but can be hijacked by some epilepsies to promote seizures.
The study, published in the journal Neuron, expanded on previous findings showing that CBD blocks the ability of the molecule LPI to amplify nerve signals in a brain region called the hippocampus.
The current study argues that, for the first time, the molecule also weakens signals that counter seizures, further explaining the value of CBD treatment and the generation of seizure activity in epileptic people.
As part of the research group, the Aston University team used a leading model of epilepsy, developed by Professor Gavin Woodhall, to perform recordings of electrical signals in brain cells taken from epileptic rodents, some of which had been treated with CBD. By doing this, they were able to pinpoint the molecular mechanisms by which CBD acts to prevent seizure activity in epileptic brains.
Professor Woodhall, co-director of Aston Institute for Health and Neurodevelopment, said: “These new insights into epilepsy and the mechanism by which CBD works to stop seizures is the fruit of years of collaboration between neuroscientists in the UK and USA and our industry partner, GW Pharma.
“We are hopeful that it will lead to even better treatments in future”.
We are delighted that our epilepsy model is being used to make such meaningful breakthroughs in the mechanisms of epilepsy and is paving the way for a wider range of future treatments”.
Dr Stuart Greenhill, senior lecturer in neuroscience, Aston Institute for Health and Neurodevelopment
Corresponding author Richard W Tsien, chair of the Department of Physiology and Neuroscience at NYU Langone Health, said: “Our results deepen the field’s understanding of a central seizure-inducing mechanism, with many implications for the pursuit of new treatment approaches.
“The study also clarified, not just how CBD counters seizures, but more broadly how circuits are balanced in the brain. Related imbalances are present in autism and schizophrenia, so the paper may have a broader impact.”
The results build on how each neuron “fires” to send an electrical pulse down an extension of itself until it reaches a synapse, the gap that connects it to the next cell in a neuronal pathway, and how this activity can change in a network which is likely to generate epileptic seizures.
Source:
Journal reference:
Rosenberg, E.C., et al. (2023) Cannabidiol modulates excitatory-inhibitory ratio to counter hippocampal hyperactivity. Neuron. doi.org/10.1016/j.neuron.2023.01.018.