## 4 Conclusions  
From the literature discussed, it is accurate to say that CBD is highly effective in slowing the onset of symptoms and the progression of disease in EAE mice that have been induced with MOG (35-55). It seems to do this by reducing the amounts of pro-inflammatory cells, microglial and T-cell activation as well as diminished axonal damage in the spinal cord and reduced cytokine expression. Additionally, it seems that when CBD is administered IP, it protects the mouse from oxidative neuronal damage and neurodegeneration. It would be inaccurate to draw from the literature which dose is most effective in doing this, as conflicting findings have repeatedly been reported, with some studies having reported doses as low as 5 mg/kg showing effective and promising results [56], whereas others reporting that only higher doses, up to 50 mg/kg, were effective [57]. Building from this, the literature clearly shows that administering drug combinations of CBD and \(\Delta^{9}\)-THC, such as nabiximabs (Saitvex), are more effective in reducing the symptoms of MS in EAE-induced mice than administering either CBD or \(\Delta^{9}\)-THC alone. This may be due in part to the compounds having a synergistic effect. While CBD reduces the amount of infiltration of pro-inflammatory cytokines: IL-17, IFN-\(\gamma\), TNF-\(\alpha\) and IL-\(\lg\)[87], \(\Delta^{9}\)-THC seems more effective in reducing clinical scores of spasticity. The results of human studies are far less encouraging. A drawback for this cohort of studies is the fact that histological analysis of cell aggregates in the spinal cord cannot be done in living humans. The literature in this area shows that cannabinoid drugs such as Sativex or ECP002A are moderately effective in reducing scores of spasticity as measured by spasticity NRS or MAS. This literature is conflicting and often difficult to decipher. A possible cause of the conflicting nature of these studies is the study design. Rightly, some studies implement a randomised double-blind placebo-controlled study design in a large sample size [88; 89], whereas others implement less favourable study designs in smaller groups. These varying designs pose significant issues for prescribing physicians as the results pose uncertainty. A slightly clearer picture is painted regarding NP. Sativex seems to be effective in reducing patient-reported measures of pain, as measured by pain NRS, but less effective in reducing objective measures of pain, measured by the MAS. Again, these findings can be contradictory. Some studies report statistically significant results whereas others report clinically relevant or non-significant results. Contradictory findings can also be seen in terms of cognition. Again, some authors report statistically significant cognitive dysfunction and cortical changes as a result of Sativex or smoked cannabis, whereas others found that cannabis use causes little to no cognitive or cortical changes. Further research is needed in this field, as currently, the findings are about as clear as mud. In animal studies, an optimal dose should be found to assess the true effect of CBD and \(\Delta^{9}\)-THC on models of MS. In humans, more randomised double-blind placebo-controlled studies are needed in a long-term patient group. By doing this, researchers will be provided with more in-depth knowledge of the effects of cannabinoid drugs on spasticity, pain, and cognition. Conceptualization, E.J. and S.V. ; resources, S.V. ; writing--original draft preparation, E.J. ; writing--review and editing, E.J. and S.V. ; supervision, S.V. All authors have read and agreed to the published version of the manuscript. This review paper work was funded by the Dublin City University Faculty of Science and Health Internship Award to Principal Investigator [PERSON] and the Behavioural Neuroscience Laboratory. [PERSON] was successfully selected as the intern to work on this review paper.