## Animal Studies
### Cannabidi Slows Symptom Onset in EAE Mice
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Ligand (Route)**} & \multicolumn{2}{c}{**Concentration (Time of**} & \multirow{2}{*}{**Species (Sex)**} & \multirow{2}{*}{**Effect**} & \multirow{2}{*}{**Reference**} \\  & **Administration in Days** & & & \\  & **Post Disease Induction** & & & \\ \hline CBD (IP) & 20 mg/kg (9–25) & C57 BL/6 (f) & \(\uparrow\) & [56] \\  & 5–10 mg/kg (0) & & & \\ CBD (IP) & 10 mg/kg (0) & C57 BL/6 (f) & \(\uparrow\) & [57] \\  & 50 mg/kg (0) & & & \\ CBD (OG) & 75 mg/kg (1) & C57 BL/6 (f) & \(\uparrow\) & [58] \\ CBD (IP) & 5 mg/kg (19–21) & C57 BL/6 (f) & \(\uparrow\) & [59] \\ CBD (IP) & 5 mg/kg (11–13) & C57 BL/6 (f) & \(\uparrow\) & [60] \\  & 5 mg/kg (210) & Biozzi ABH (m/f) & \(\uparrow\) & [61] \\  & 10 mg/kg (210) & & & \\ CBD.A\({}^{9}\)-THC (SC) & 10 mg/kg (11) & C57 BL/6 (f) & \(\uparrow\) & [62] \\  & 20 mg/kg (11) & C57 BL/6 (f) & \(\uparrow\) & [62] \\  & 20 mg/kg (11) & C57 BL/6 (f) & \(\leftarrow\) & [62] \\ CBD.A\({}^{9}\)-THC (SC) & 10 mg/kg (10–15) & C57 BL/6 (f) & \(\uparrow\) & [63] \\ CBD (SC) & 20 mg/kg (10–15) & C57 BL/6 (f) & \(\leftarrow\) & [63] \\ \(\Delta^{9}\)-THC (SC) & 20 mg/kg (10–15) & C57 BL/6 (f) & \(\uparrow\) & [63] \\  & 10 mg/kg (10–15) & C57 BL/6 (f) & \(\uparrow\) & [64] \\ CBD.A\({}^{9}\)-THC oil extract (OG) & 215 mg/kg (6–18) & [PERSON] (f) & \(\uparrow\) & [65] \\ CBD oil extract (OG) & 215 mg/kg (6–18) & [PERSON] (f) & \(\leftarrow\) & [65] \\ \(\Delta^{9}\)-THC oil extract (OG) & 215 mg/kg (6–18) & [PERSON] (f) & \(\leftarrow\) & [65] \\ \hline \hline \end{tabular}  
* IP = intra peritoneal; OG = oral gavage; IV intravenous; SC = subcutaneous; f = female; m = male; \(\uparrow\) = positive reduction in symptomatology and histological markers; — = no significant change in symptomatology and histological markers.  
\end{table} 
Table 1: Summary of the effects of cannabinoids on EAE mouse models of multiple sclerosis. that EAE mice treated with CBD showed a greater trend of recovery compared to the EAE only mice. They also found that by treating mice with CBD, they were able to preserve the paw sensibility response in EAE mice. Histological analysis from this study revealed that mitogen-activated protein kinases (MAPK) signaling pathway is strongly activated by EAE induction, and, repeated administration of CBD reduces the levels of expression and thwarts neuronal death. This is consistent with the findings of [PERSON] and [PERSON] who have written extensively on the topic [67]. Similarly to findings from the studies presented above, [PERSON] and colleagues [58] found that treating EAE induced mice with oral CBD earlier than other studies reduced the clinical disease score, again in C57 BL/6 mice. Histological analysis from this study showed that mice which had received treatment with oral CBD had significantly reduced levels of myelin derived suppressor cells. Similar to these articles, it was reported that there were fewer cell infiltrates and T cells in the white matter tracts of the cerebellum. From this, the authors concluded that CBD has a role in reducing neuroinflammation in the cerebellum. This study reported an increase in IFN-\(\gamma\) which conflicts with the findings of [PERSON] [56] who reported that CBD can reduce the amounts of IFN-\(\gamma\) available. [PERSON] et al. differed in their approach in that they decided on a low dose of 5 mg/kg of CBD from studies on rheumatic arthritis that use cannabinoids. Even with a low dose of CBD, their histological analysis showed diminished axonal damage, as well as microglial activation and T-cell activation in the spinal cord with reductions in clinical scores being visible from day 23 post EAE induction. [PERSON] et al. found very similar results and found that treating EAE-infected mice with CBD caused a reduction in neurobehavioural scores, reduced inflammation, demyelination, axonal damage, and cytokine expression in C57 BL/6 mice treated with a low dose of 5 mg/kg administered IP.