M.Sc Thesis


M.Sc StudentEuhus Benjamin David
SubjectThe Effect of Cannabis on the Mobility and Viability of the
BV-2 Microglia Cell Model
DepartmentDepartment of Biology
Supervisor DR. David Meiri
Full Thesis textFull thesis text - English Version


Abstract

Microglia are the primary defenders of the central nervous system. Their migration plays a paramount role in their function. Cannabinoid compounds from Cannabis sativa and endogenously produced endocannabinoids have been previously shown to stimulate microglia migration in vitro and in vivo, although no studies have been presented using whole extracts of Cannabis. With a classification as a Schedule I drug in most countries, research with whole plant Cannabis only exists in extremely exceptional cases. Conversely, it is one of the most widely used and distributed illicit substances. Due to microglia’s essential role in cell function, we sought to determine the potentially varied effect of multiple Cannabis chemovars on microglia behavior, specifically mobility, using a BV-2 cell line. Using 21 unique extracts local to Israel we were able to demonstrate the stimulatory and inhibitory effects on the mobility of microglia using a scratch and Transwell assay. Cannabis induced migrational changes were found to involve CB2 receptor, and possibly TRPV1 receptor, and were dependent on an upregulation of Calmodulin through influxes of calcium. Using a high performing, High CBDA extract, five fractions were created via HPLC fractionation and tested in various combinations.  Using combinations of fractions, we were able to demonstrate the increased efficacy of whole extract versus isolate compounds. This study demonstrates that Cannabis’ effect on migration can be varied and is due to more than dominant cannabinoid. These effects may be potentially therapeutic for conditions related to dysfunctional microglia such as Multiple Sclerosis and Alzheimer’s Disease.