## Animal Studies
### Cannabidi Slows Symptom Onset in EAE Mice
The authors found that these effects were visible on day 16 and concluded that CBD prevents against oxidative neuronal damage and neurodegeneration. These studies show that CBD is in fact effective in delaying symptom onset of EAE and slows disease progression. Combinations of \(\Delta^{9}\)-THC and CBD Are More Effective in Symptom Relief and Neuroinflammation Reduction  
From reviewing the literature, it appears that, a combination of \(\Delta^{9}\)-THC and CBD is more effective in reducing the symptoms associated with an animal model of MS compared to administration of \(\Delta^{9}\)-THC or CBD _per se_. This formulation has been achieved in the drug (6a_R_,10a_R_)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol;2-[(6_R_)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol (nabiximabs; Sativex). Sativex is a herbal preparation containing a defined quantity and standardized extracts of \(\Delta^{9}\)-THC and CBD formulated for oromucosal spray administration with potential analgesic activity, together with other minor cannabinoids, flavonoids, and terpen, all derived from two cannabis plant varieties. In a 2012 study, researchers compared the effects of Sativex, a compound combining \(\Delta^{9}\)-THC and CBD in a 1:1 ratio, to a positive control of baclofen, a frontline treatment for muscle spasticity associated with MS or spinal cord injury [61]. Five mg/kg of Sativex were administered SC with the benefits being seen within 10 min and lasting for at least two hours. It was reported that this administration reduced peak spasticity by 20%. In another group, 10 mg/kg of Sativex were also administered SC. In this group, a peak reduction in spasticity of 40% was observed. The benefits observed in the higher dose group were the same as was observed in the baclofen positive control group, where a 40% peak spasticity reduction was found. It was deduced that \(\Delta^{9}\)-THC caused this reduction of spasticity due to its CB\({}_{1}\) agonistic properties whereas CBD reduced the levels of cell infiltrates due to its PPAR-gamma association. The authors reported mild sedation as the only side effect of cannabis treatment. This is a great advantage over the current frontline treatment of baclofen which has several notable side effects such as seizures, drowsiness, fatigue, abdominal pain, underdose and overdose [30; 31]. If this self-titrating oromucosal drug, which allows the user to achieve their own optimum dose, is as effective as current frontline treatments such as baclofen, but exhibits more favourable side-effects, does this drug have potential to be the new first-line treatment?More recently in 2015, [PERSON] and colleagues [62] administered Sativex at 10 mg/kg. The authors reported that Sativex significantly mitigated the neurological symptoms in EAE, while reducing the number and extent of cell aggregates in the spinal cord of these mice. It was found that CBD alone would only delay symptom onset and did not reduce cell aggregates. This conflicts with the literature depicted previously, where it was found that CBD does indeed reduce cell aggregation infiltrating the spinal cord. In 2019, several authors began to examine in-depth, the effects of administering \(\Delta^{9}\)-THC and CBD in mice. As seen in other studies, [PERSON] et al. [63] administered a 10 mg/kg combination of \(\Delta^{9}\)-THC and CBD in a 1:1 ratio. Their results showed that the combination of the two compounds reduced neuroinflammation and suppressed cell infiltration of TH1 and TH17 pro-inflammatory cytokines, as well as reducing IL-17, IFN-\(\gamma\), Tumour necrosis factor \(\alpha\) (TNF-\(\alpha\)) and IL-\(\beta\) while suppressing pro-inflammatory phenotypes. This is somewhat consistent with the literature described above which found that CBD alone could reduce the amounts of pro-inflammatory cytokines and promote anti-inflammatory cytokines.