In C57BL/6 mice, inflammation and neuronal demyelination were individually decreased by CBD and PEA (Rahimi et al., 2015).
However, anti-inflammatory and anti-demyelinating activities were shown to be decreased by co-administration of both cannabinoids, proposing antagonism between both cannabinoid pathways.
In a mouse model of MS, Sativex oromucosal spray (50% THC and 50% CBD) was compared with each phytocannabinoid alone to assess their effect. It was observed that motor deterioration was similarly reduced by CBD-BDS and Sativex, whereas THC-BDS exhibited a weaker effect. The effect of CBD was via PPARγ receptors while THC effect was via CB2 and primarily CB1 receptors (Feliú et al., 2015).
In the rat model of experimental autoimmune encephalitis / multiple sclerosis, it was found that CBD exhibits immunoregulatory activities through induction of CD4+CD25−CD69+LAG3+ cells in MOG35-55-activated APC/TMOG co-cultures (Kozela et al., 2015).
Gene profiling found that CBD exhibits its immunoregulatory activities in activated memory TMOG cells via inhibiting pro-inflammatory genes, T cell proliferation, and potentially T-cell memory while enhancing anti-inflammatory genes (Kozela et al., 2016).
In the Experimental Autoimmune Encephalitis (EAE) mouse model of Multiple Sclerosis, it was shown that daily use of a 1% CBD cream could exhibit neuroprotective activities against EAE (Giacoppo et al., 2015).