## 3 Human Studies
### Cannabinoids Are Only Moderately Effective in Reducing MS Related Spasticity
\begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline
**Adverse Event** & [69] & [70] & [71] & [72] & [73] & [74] & [75] & [76] & **Total** \\ \hline Dizziness & 5 & 7 & 13 & 35 & 4 & 34 & 50 & 4 & 152 \\ Headache & 0 & 0 & 9 & 0 & 0 & 7 & 9 & 3 & 208 \\ Somnolence & 0 & 0 & 9 & 11 & 0 & 16 & 0 & 0 & 36 \\ Muscle Weakness & 3 & 2 & 5 & 0 & 0 & 1 & 0 & 3 & 14 \\ Spasticity & 0 & 0 & 3 & 4 & 0 & 0 & 0 & 0 & 7 \\ Parasesthesia & 0 & 0 & 2 & 0 & 0 & 0 & 0 & 0 & 2 \\ Tremor & 0 & 0 & 3 & 0 & 0 & 0 & 0 & 1 & 4 \\ Vertigo & 2 & 1 & 0 & 0 & 0 & 16 & 34 & 4 & 57 \\ Tinnitus & 0 & 0 & 2 & 0 & 0 & 0 & 0 & 2 \\ Mood Disruption & 0 & 0 & 0 & 0 & 2 & 0 & 1 & 3 \\ Euphoria & 0 & 0 & 9 & 0 & 0 & 0 & 1 & 10 \\ Attention & 0 & 0 & 1 & 0 & 2 & 6 & 0 & 11 & 20 \\ Insomnia & 0 & 0 & 1 & 0 & 0 & 0 & 2 & 0 & 3 \\ Fatigue & 5 & 0 & 5 & 29 & 2 & 16 & 25 & 6 & 88 \\ Feeling abnormal & 0 & 0 & 5 & 50 & 0 & 5 & 0 & 0 & 60 \\ Feeling hot & 0 & 3 & 0 & 0 & 0 & 0 & 0 & 3 \\ Oral Discomfort & 4 & 0 & 3 & 0 & 19 & 13 & 5 & 44 \\ Nausea & 2 & 0 & 1 & 0 & 0 & 12 & 17 & 2 & 34 \\ Appetite & 0 & 0 & 2 & 3 & 0 & 0 & 0 & 5 \\ Stomatitis & 1 & 0 & 0 & 0 & 0 & 0 & 0 & 0 & 1 \\ Incontinence & 1 & 0 & 0 & 0 & 0 & 0 & 0 & 0 & 1 \\ Hypertension & 0 & 1 & 0 & 0 & 0 & 8 & 0 & 0 & 9 \\ Pharyngobia & 0 & 1 & 0 & 0 & 0 & 2 & 0 & 0 & 3 \\ Vision Blurred & 0 & 0 & 0 & 0 & 4 & 0 & 0 & 4 \\ Diarrhoea & 0 & 0 & 0 & 0 & 0 & 7 & 13 & 0 & 20 \\ Vomiting & 0 & 0 & 0 & 0 & 0 & 5 & 0 & 0 & 5 \\ Memory & 0 & 0 & 0 & 0 & 6 & 0 & 0 & 6 \\ Impairment & 0 & 0 & 0 & 0 & 0 & 5 & 0 & 0 & 5 \\ Tychomotor & & & & & & & & & 806 \\ Impairment & & & & & & & & & & \\ Total Adverse & & & & & & & & & & \\ Events & & & & & & & & & & \\ Total Participants & 166 & 22 & 24 & 144 & 28 & 312 & 333 & 17 & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Frequencies of adverse events of MS patients treated with cannabinoids from studies where frequencies were reported. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Ligand** & **Chemical Name** & **Reference** \\ \hline \multirow{4}{*}{Nabiximols (Sativex)} & (6a\(R\),10a\(R\))-6,6,9-trimethyl-3-pentyl-6a,7,8,10a- \\  & tetrahydrobenzo[c]chromoment-1-ol-2-(6(R)-3-methyl-6-propyl-1-en- \\  & 2-ylyclohex-2-en-1-yll-5-pentylbenzene-1,3-diol \\ \(\Delta^{9}\)-tetrahydrocannabinol (-)-(6a,R,10a\(R\))-6,6,9-trimethyl-3-pentyl-6a,7,8,10a- \\ (Dronabinol) & tetrahydroc-6H-benzo[c]chromoment-1-ol \\ ECP002A & (-)-(6a,R,10a\(R\))-6,6,9-trimethyl-3-pentyl-6a,7,8,10a- \\ tetrahydroc-6H-benzo[c]chromoment-1-ol \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Cannabinoid ligands used in human studies of spasticity, pain and cognition. develop psychotic symptoms than those who consume preparations with low \(\Delta^{9}\)-THC and CBD ratios. Sativex relieves spasticity and pain in multiple sclerosis more effectively than \(\Delta^{9}\)-THC alone, possibly because CBD's effects allow patients to tolerate higher amounts of \(\Delta^{9}\)-THC. CBD may also supplement the antispastic effects of \(\Delta^{9}\)-THC, possibly through local potentiation of glycine signaling, inhibition of endocannabinoid degradation, or retardation of demyelination through anti-inflammatory, antioxidant, and anti-excitotoxic mechanisms [79].