Investigating cannabinoid modulation of endosomal toll-like receptor signalling

The cannabis plant, Cannabis sativa L., contains many bioactive compounds of interest such as cannabinoids, terpenes, and flavonoids. Plant-derived phytocannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are of great interest in immunological research due to their anti- inflammatory properties. The use of cannabinoid-based therapeutics in autoimmune conditions such as multiple sclerosis (MS) further underscores their immunomodulatory therapeutic potential, however the exact mechanisms of action underlying their clinical efficacy remain to be elucidated. Of particular interest to our laboratory is the impact of cannabinoid treatment on innate immune signalling. Indeed, cannabinoids have been previously demonstrated to modulate the inflammatory signalling of a family of innate immune receptors termed the toll-like receptors (TLRs). Given that TLRs are important mediators of the immune response, and that TLRs have been indicated to play a role in MS disease pathogenesis, the targeting of TLRs by cannabinoids is an important and novel area of investigation. This study aimed to elucidate the impact of cannabinoids on TLR7/8/9-mediated inflammatory signalling using in vitro models of inflammation. The effects of Δ9-THC and CBD treatment were examined in human macrophage cell lines and primary immune cells. Furthermore, using a bank of human post-mortem specimens, this study aimed to investigate the neuropathological changes in the endocannabinoid and innate immune system associated with MS pathology. Our study has demonstrated promising anti-inflammatory effects of cannabinoids.

 

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Publication History

Article published online:
16 November 2023