Table 2.

The effects of cannabinoids in CNS and periphery in in vivo studies of neurodegenerative diseases.

Cannabinoids	Disease, Model	Effects in CNS	Effects in Periphery	References
10 mg/kg each of THC+CBD (1:1 ratio)	MS, EAE animal models	Reduced disease severity; reduced LPS levels in the brain	Reduced IL-17A and IFN-γ and increased MDSCs in splenocytes; increased short-chain fatty acids in gut microbiome; reduced Akkermansia muciniphila in feces	[221]
CBD 20 mg/kg	MS, EAE animal models	Attenuated disease severity, increased MDSCs, and reduced CXCL9, CXCL10, and IL-1β expression	Increased MDSCs and monocytes in the spleen, decreased neutrophils in mesenteric lymph nodes, and suppressed systemic inflammation in the GI tract	[239]
CBD 4.3 mg/kg	PD, transgenic mouse model	Improved motor deficits and prevented αSyn aggregation	Downregulated pathologic metabolites that participate in arginine biosynthesis and histidine metabolism	[233]
CBD 75 mg/kg	MS, EAE animal models	Reduced clinical disease, neuroinflammation in the cerebellum, and T cell infiltration into spinal cord	Suppressed IFN-γ-producing CD8+ T cells in the spleen	[29]
CBD 20 mg/kg	MS, EAE animal models	Attenuated EAE disease progression; MDSCs increased in spinal cord and brain	Reduced IFNγ and IL-17 and increased IL-10 production in the spleen; peritoneal MDSCs elevated	[186]
CB2 agonist, HU-308, 15 mg/kg	MS, EAE animal models	Improved EAE symptoms and reduced spinal cord lesions, microglial activation, and chemokine receptors	Downregulation of chemokines CCL2, CCL3, CCL5 and their receptors CCR2 and CCR1 in bone marrow	[76]
CB2 agonist, Gp1a, 5 mg/kg	MS, EAE animal models	Attenuated EAE development, limited infiltration of CD4 T cells, downregulated pro-inflammatory genes in spinal cords	Suppressed expression of chemokine receptors in splenic T cells	[84]