Table 5.

Cannabidiol Effects in Experimental Autoimmune Encephalomyelitis

Model	Approach	Dosage/concentration	Effects	Reference
EAE in ABH	In vivo	In vivo: 0.5–25 mg/kg i.p.	No effects	211
EAE in C57BL/6	In vivo and in vitro	In vivo: 5 mg/kg i.p. in vitro: 1, 5, and 10 μM	in vivo: ↓disease severity, ↓T cell infiltration into the CNS, ↓microglial activation, ↓axonal damage in vitro: ↓T cell proliferation	163a
TMEV in SJL/J	In vivo and in vitro	In vivo: 5 mg/kg i.p. in vitro: 1 and 5 μM	in vivo:↓disease severity, ↓leukocyte infiltration into the CNS, ↓microglial activation, ↓CCL2 (MCP-1), ↓CCL5, ↓IL-1β ↓TNF-α in vitro: ↓sVCAM-1 production from endothelial cells, ↓leukocyte adhesion, ↓CCL2 (MCP-1)	164a
MOG35–55-specific T cells from EAE mice	In vitro	In vitro: 0.1, 1, and 5 μM	in vitro: ↓IL-17A, ↓IL-6, ↑IL-10	144a
MOG35–55-specific T cells from EAE mice	In vitro	In vitro: 5 μM	in vitro:↓IL-17A, ↓IL-6, ↑IL-10, ↑EGR2, ↑CD4+CD25−CD69+LAG3+ phenotype, ↑STAT5/↓STAT3, ↓B cell activity, ↑Nfatc1, ↑Casp4, ↑Cdkn1a, ↑Icos, ↑Fas	153a
EAE in C57BL/6	In vivo	In vivo: 5 mg/kg i.p.	in vivo: ↓disease severity, ↓leukocyte invasion, ↓demyelination, ↓TNF-α, ↓IFN-γ, ↓IL-17A	212
EAE in C57BL/6	In vivo	In vivo: 10 mg/kg i.p.	in vivo: ↓disease severity, ↓FAS ligand, ↓ERK phosphorylation, ↓Caspase-3 activity, ↓Bax/↑Bcl-2, ↓p53-p21 activation, ↓apobody formation	166a
MOG35–55-specific T cells from EAE mice	In vitro	In vitro: 5 μM	in vitro: ↓IL-1β, ↓IL-3, ↓Xcl1 mRNA, ↓IL-12a mRNA, ↑Dusp6 mRNA, ↑Btla mRNA, ↑Lag3 mRNA, ↑Irf4 mRNA, ↑IL-10 mRNA	143a,b
EAE in C57BL/6	In vivo	In vivo: 10 mg/kg i.p.	in vivo: ↓disease severity, ↓leukocyte infiltration, ↑PI3k/Akt/mTOR phosphorylation, ↑S6k phosphorylation, ↑BDNF expression, ↑PPAR-γ, ↓IFN-γ, ↓IL-17A, ↓JNK activity, ↓p38 MAP kinase activity	167a
Adoptive Transfer EAE in C57BL/6	In vivo and in vitro	In vivo: 5–50 mg/kg i.p in vitro: 1, 5 & 10 μM	in vivo: ↓disease severity, ↓leukocyte invasion, ↓demyelination, ↓axonal damage, ↓microglial activation, ↓CB2 receptor expression in CNS, ↓GPR55 receptor expression in CNS in vitro: ↓Cell viability, ↓IL-6, ↑apoptosis, ↑ROS	165a
EAE in C57BL/6	In vivo	In vivo: 20 mg/kg i.p	in vivo: ↓disease severity, ↓leukocyte invasion, ↓IL-17A, ↓IFN-γ, ↓RORγT, ↓T-bet, ↑IL-10, ↑MDSC ex vivo: ↓IL-17A, ↓IFN-γ, ↑IL-10	137a

^aDiscussed in review.

^bSee¹⁴⁰ for a full description of the microarray results.

CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; ERK, extracellular signal-regulated kinase; STAT, signal transducer and activator of transcription; TMEV, Theiler's murine encephalomyelitis virus.