People with brain tumours frequently experience tumour-associated seizures, which respond poorly to antiseizure medication. Cannabis-based treatments have the potential to fill this therapeutic gap. The medicinal use of cannabis extracts is however, controversial. One key issue for cannabis-based treatments of seizures is that their mechanism of action is unclear.
Hence, we propose a project to investigate the anti-seizure mechanisms of two common phytocannabiniods, ?9-tetrahydrocannabidiol (THC) and Cannabidiol (CBD) using ex vivo living human brain tissue, donated by individuals who are undergoing brain tumour surgery. The live human brain tissue generates spontaneous seizure-like discharges.
Year 1: Local field potential recordings to identify spontaneous epileptic discharges in peritumoural cortex. Wash on Cannabidiol and THC separately and together to determine dose-response curves for their effects on seizure discharges.
Year 2: Investigate the mechanisms of the anticonvulsant effects of CBD and THC, focusing on excitatory circuitry. The student will use patch-clamp recording of visualised pyramidal neurons to study changes in neuronal excitability and excitatory neural circuitry and whether CBD and THC block the proconvulsant effects of glutamate release by glioma cells.
Year 3: Evidence suggests that Inhibition in the peritumoural cortex is reduced, which contributes to tumour-associated seizures. The student will therefore assess whether CBD and THC boost inhibition to suppress seizure discharges.
Recorded neurons will be filled with a fluorescent dye and biocytin for imaging after recording has finished. The extent of tumour infiltration in recorded human brain tissue will be assessed by labelling the tumour cells and the excitatory and inhibitory neurons.