Effects of Orally Administered Cannabidiol on Neuroinflammation and Intestinal Inflammation in the Attenuation of Experimental Autoimmune Encephalomyelitis

AbstractCannabidiol (CBD) is a bioactive compound isolated from Cannabis plants that has garnered attention within the medical community due to its potent anti-inflammatory properties. To better understand how CBD limits excessive neuroinflammation we administered CBD via oral gavage (20 mg/kg) in a murine model of multiple sclerosis (MS) known as experimental autoimmune encephalomyelitis (EAE). Using single cell RNA sequencing (scRNA Seq) and array-based transcriptomics we were able to delineate how CBD limits excessive inflammation within the central nervous system (CNS) as well as within the intestinal lining in EAE. In-depth scRNA Seq analysis of CNS tissue demonstrated that CBD treatment resulted in a significant reduction in CXCL9, CXCL10 and IL-1 β expression within the CNS, leading to inhibited infiltration of inflammatory macrophages. CBD inhibited IL-1β production independent of the classical cannabinoid receptors, CB1 and CB2. CBD treatment also led to induction of Myeloid-derived Suppressor Cells (MDSCs) both in the CNS and periphery. Interestingly, CBD treatment of EAE mice revealed significant suppression of inflammation in the gastrointestinal (GI) tract. The intestinal epithelial cells (IECs) of CBD treated mice demonstrated a transcriptional inhibition of a family of pyroptosis initiators that drive localized inflammation k nown as gasdermins (GSDMs). Further investigation into the GI tract via 16s sequencing of cecal and fecal contents demonstrated that or...
Source: Journal of NeuroImmune Pharmacology - Category: Drugs & Pharmacology Source Type: research