Title : Cannabinoid acids for the treatment of multiple sclerosis
Abstract:
Penetration of immune cells into the brain, activation of glia and secretion of inflammatory mediators like cytokines and free radicals like nitric oxide (NO) play key role in Multiple sclerosis (MS); an autoimmune disease. Phytocannabinoidshave anti-inflammatory properties. All phytocannabinoids originate from cannabigerolic acid, which is converted to tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). These acid derivatives contain chemical groups similar to those identified in Nonsteroidal Anti-Inflammatory Drugs. Thus, acid derivatives of phytocannabinoids may modulate neuroinflammation and MS.In the present study, we examined the effect of CBDA and THCA on NO, TNFα, and IL17A production in BV2 microglia activated by lipopolysaccharide (LPS), vs. neutral derivatives, CBD and THC. In vivo, we followed the clinical score in myelin oligodendrocyte glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE) mice model of MS. CBDA decreased LPS-induced NO production in BV2 cells. THCA also abrogated LPS-induced NO production in BV2 cells CBDA and THCA increased TNFα secretion from LPS-stimulated BV2 cells. CBDA decreased IL17A secretion, respectively. Treatment with THCA reduced IL17A production. CBDA treatment improved MS clinical score versus the MOG group in an in vivo EAE model. We have shown the potential of CBDA and THCA in the regulation of neuroinflammation in vitro and in vivo, it may lead to a potential therapy for neuroinflammatory diseases such as MS.