M.Sc Thesis


M.Sc StudentAmsalem Keren
SubjectEvaluating Different High-CBD Cannabis
Strains for Epilepsy Treatment
DepartmentDepartment of Biology
Supervisor DR. David Meiri
Full Thesis textFull thesis text - English Version


Abstract

Epilepsy is a neurological disorder characterized by episodes of disturbed brain activity resulting in recurrent seizures. Many possible treatments reduce the seizures’ intensity and frequency, and yet 33% of the patients remain pharmaco-resistant. In the last years, high-cannabidiol (CBD) cannabis strains are being used to reduce seizures in pharmaco-resistant patients. Today, therapists prescribe cannabis strains based only on their CBD content, without addressing all the other unique compounds found in each strain.

There are many high-CBD cannabis strains, with different chemical compositions, that are available for patients. However, cannabis extracts contain more than 500 different molecules, including phytocannabinoids, terpenes, and phenolic compounds, which have different therapeutic properties.

This research aimed to evaluate whether the different cannabinoids profile of each high-CBD cannabis strain affects their potential use as anti-convulsant. For this propose, we profiled the cannabinoid composition of four different high-CBD cannabis strains using a mass-spectrometry, coupled to liquid chromatography (LC-MS), and found that each of the tested strains has a unique phytocannabinoid profile. In order to evaluate the different high-CBD cannabis strains anti-convulsion properties, we used a chemically induced convulsions mice model of Pentylenetetrazol (PTZ).

In this research, we demonstrate that not all high-CBD cannabis strains have the same anti-convulsion properties using both behavioral and neuronal activity measurements. We show that different phytocannabinoids can penetrate the blood-brain-barrier (BBB) into the brain tissue and their composition in the brain depends on the extract cannabinoids profile. According to our results, the presence of these phytocannabinoids did not affect the endocannabinoid profile in the brain. Using endocannabinoids system receptors antagonists, we show that the cannabinoid receptor 1 (CB1) and transient receptor potential cation channel subfamily V member 1 (TRPV1) pathways are involved in the anti-convulsion effect when the CB1 pathway is anti-epileptogenic and the TRPV1 pathway is pro-epileptogenic. Lastly, we isolated the CBD fraction of different high-CBD cannabis strains and were able to identify a small group of phytocannabinoids and terpenes that are probably responsible for the anti-convulsion effect.

These results provide valuable insights regarding the use of high-CBD cannabis treatment in epilepsy. We demonstrated that the anti-convulsion effect of different high-CBD cannabis strains depends on their specific cannabinoids profile. This raises a crucial need to further analyze the cannabinoids profile in each strain and to customize the cannabis epilepsy treatment in order to optimize its therapeutic effects.