Cannabidiol (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-1β 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 known as
gasdermins (GSDMs). Further investigation into the GI tract via 16s sequencing of cecal and fecal contents demonstrated that
oral administration of CBD resulted in no significant changes in the intestinal microbiota composition. These findings demonstrate the beneficial effect of CBD treatment on autoimmune
neuroinflammation by ablating expression of pro-inflammatory
chemoattractants, regulating inflammatory macrophage activity, promoting MDSC expansion, and limiting the systemic low-grade
inflammation in the GI tract, culminating in the attenuation of EAE.