טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentRony Chanoch
SubjectEffect of Cannabis on Microglial Cell Functions
DepartmentDepartment of Biology
Supervisor Dr. Meiri David
Full Thesis textFull thesis text - English Version


Abstract

Microglia are the immune cells of the central nervous system (CNS). In response to damage or disease, microglia undergo complex activation processes that are determined by their environment. They have an important role in the healthy brain, by acting as the sentinels of the brain and maintaining homeostasis. To perform these functions, microglia adopt different activation phenotypes depending on the local environment. In damage or disease, their functions include: migration to sites of injury, release of cytokines, and phagocytosis, including the phagocytosis of amyloid-βeta, which forms the senile plaques in Alzheimer’s disease (AD). Microglia are known to have the ability of phagocytosing amyloid-βeta, but in AD brains, microglia are unable to uptake the amyloid plaques. 

The therapeutic potential of Marijuana and its active compounds, called cannabinoids, have been recently rediscovered and studied in many medical studies, including as a potential therapeutic in Alzheimer’s disease. More than 120 cannabinoids have been identified within the Cannabis plant, and extracts created from different Cannabis strains have a unique cannabinoid profile and a differential biological effect on cells.

The effect of cannabinoids on cells, both from Cannabis and endogenous cannabinoids, or endocannabinoids, is mediated by the endocannabinoid system. Microglia have a functional endocannabinoid signaling system, composed of cannabinoid receptors and the complete machinery for the synthesis and degradation of endocannabinoids. The expression of cannabinoid receptors and the production of endocannabinoids have been related to the activation profile of these cells and therefore, their specific phenotype.

There are some studies that show that cannabinoids, as well as cannabinoid receptor agonists or antagonists, have an effect on microglial migration, phagocytosis, and cytokines released, but no studies have focused on the effect of whole Cannabis extracts on these functions. In addition, few works on cannabinoids in general have focused on the acid form of cannabinoids.

We have shown that Cannabis extracts in their native form, where the cannabinoid acids have not gone through decarboxylation, increased microglial migration, phagocytosis of amyloid-βeta, and decreased in the release of pro-inflammatory cytokine, TNF-α. In addition, we have shown that the native Cannabis extracts were able to block the LPS-inhibition of phagocytosis of amyloid-βeta. We therefore propose that Cannabis extracts in their native form can be especially relevant as a therapeutic in Alzheimer’s disease. These results are opening the door for more comprehensive research for the optimization of preclinical Cannabis-based therapies for Alzheimer’s disease.