This project aims to identify novel targets for testing cannabinoids in animal models of disease and enable future drug discovery ventures for epilepsy and other disorders.
One of the major, yet relatively uninvestigated, targets for cannabinoids is the family of receptors in the brain known as Cys-loop receptors. Cys-loop receptors are among the most prevalent in the brain and play a vital role in regulating the excitability of neurons. Examples include GABAA, nicotinic acetylcholine, glycine, and serotonin type 3 (5-HT3) receptors. These receptors are implicated in a range of disorders, including epilepsy, pain, dementia, anxiety, addictions and depression. They are also heavily implicated in neuroprotection, sleep, memory and learning, and social behaviour. Many drugs on the market target these receptors, including benzodiazepines, anaesthetics, the drugs used to prevent chemotherapy-induced nausea, and a number of anticonvulsants.
Naturally occurring genetic mutations in these receptors, or ‘channelopathies’, can lead to changes in the way that Cys-loop receptors function and/or the receptor’s expression in the brain and other organs. This can result in disorders such as epilepsy, myasthenia gravis and hyperekplexia (startle disease). Elucidating direct actions of cannabinoids on these receptors may provide mechanisms for treating such conditions.
The major aims of the project are to determine structure-activity relationships for multiple cannabinoids at Cys-loop receptors, to identify novel targets for testing cannabinoids in animal models of disease, and enable future drug discovery ventures for epilepsy and other target disorders based around actions at these receptors.
An early breakthrough was our discovery of direct actions of cannabidiol (CBD) at certain types of GABAA receptors, recently published in the journal, Pharmacological Research.
Drug discovery and development, cellular disease models.
Commenced in 2016
The Lambert Initiative
This project has identified specific phytocannabinoids of interest for a range of disorders.Initial findings suggest specific phytocannabinoids may offer advantages over existing medications for certain disorders. As a result, we have progressed a number of the early leads identified in this project into testing in pre-clinical models of disorders, including epilepsy, anxiety disorders, pain, and sleep disorders.
Some of the important findings from this research were published in the international journal Pharmacological Research in May 2017.