Discovery That Cannabidiol Acts Over GABA Neurons Could Explain its Antiepileptic Properties

Article by Ricardo Oliveira, Lift News

Discovery that cannabidiol acts over GABA neurons could explain its antiepileptic properties The mechanism unveiled by the authors offers a compelling explanation for some of the anticonvulsant, analgesic and anxiolytic effects of CBD that have been reported in clinical practice

GABA is one of the basic neurotransmitters of the human brain. It is responsible for a sharp inhibition of neuronal activity, which is required to maintain complex firing patterns across widespread brain networks. Having such a fundamental role, it is no surprise that malfunctions in this system are associated with a myriad of brain disorders that include epilepsy, insomnia, anxiety, stroke and schizophrenia.

The different functions of GABA are determined by the location of its receptors as well as their specific structure. Each GABA receptor is comprised of 5 proteins drawn from a pool of 19 potential proteins, with different configurations determining what substances can activate them and how they work regarding potency, speed and duration of action.

Discovery that cannabidiol acts over GABA neurons could explain its antiepileptic properties The mechanism unveiled by the authors offers a compelling explanation for some of the anticonvulsant, analgesic and anxiolytic effects of CBD that have been reported in clinical practice

Synthetic drugs like benzodiazepines, barbiturates and general anesthetics, as well as natural compounds like kavalactones (from the Kava plant) and flavonoids, exert their effects on humans by binding specifically to GABA receptors and altering their activity.

Endocannabinoids can modulate GABA activity too. When a neuron is under extreme inhibition due to GABA activity, it can synthesize 2-AG and anandamide and send them to the previous neuron whereupon they bind to CB1 and CB2 receptors, leading to a cascade of molecular reactions that ultimately reduces GABA release. Recently, it has been found that the endocannabinoids can also act directly on GABA receptors in a way that is very similar to how the abovementioned drugs work.

This finding could help explain how cannabidiol (CBD), which unlike its cousin THC is not able to activate neither CB1 or CB2 receptors, nevertheless exerts actions that strikingly resemble those of other GABA-mediated drugs. To explore this idea, Dr. Mary Chebib and other researchers from the University of Sydney conducted a highly technical investigation measuring the effects of CBD on human GABA receptors. Their report was recently published in the journal of Pharmacological Research.

The authors started by expressing different types of human GABA receptors in the egg cells of Xenopus frogs (a widespread model for physiological and genetic studies). Next, they inserted two electrodes to measure fine changes in electrical current following GABA administration and  exposure to either CBD or 2-AG.

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