## 2 Phytocannabinoids (PCs), Endocannabinoids (ECs) and Synthetic Cannabinoids (SCs)
### Synthetic Cannabinoids (SCs)  
The third group of cannabinoids consists of synthetic analogs of both ECs and PCs groups, appositely designed by scientists in the field, to enhance the benefits and therapeutic properties of ECs and PCs, while reducing the psychotropic and adverse effects. Among others, they include the compounds reported as examples in Figure 6 (chemical structures), and Table 3 (pharmacological properties and selectivity for receptors CB1 and CB2), which have demonstrated to be promising for treating severe humans' chronic diseases including breast and prostate tumors, the unpleasant side-effects of chemotherapy, and chronic pain [42]. Figure 5: Chemical structure of two THC metabolites (11-NCTHC and 11-HTHC) and of two products deriving from CBCA degradation. Figure 6: Structure of some SCs capable to act on CB1 and/or CB2 receptors. \begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**SCs**} & \multicolumn{3}{c}{**Binding Affinity**} & **Effects** & **Refs.** \\ \cline{2-5}  & **CB1 (Ki, nM)** & **CB2 (Ki, nM)** & & **Appetite stimulant** \\  & & & **Psychotropic effects** & [60] \\ \hline Methanandamide & & & & \(\downarrow\) Nausea \\ (AM-356) & 20 & 815 & & Antienetic \\ \hline SR144528 & 280 & 0.1 & Anti-inflammatory & [48] \\ \hline Cannabinor \({}^{\#}\) (PRS-211,375) & 5585 & 17.4 & \(\downarrow\) Neuropathtic pain & [62] \\ \hline CP47,597 & 2.1 (Kd) & 56 & Analgesic & [48] \\ \hline JTE907 & 490 & 2.2 & Anti-inflammatory & [48] \\ \hline JWH133 & 680 & 3.4 & \(\downarrow\) Neurotoxicity & \\  & & & \(\downarrow\) Alzheimer symptoms & [48] \\ \hline AM1241 & 272 & 3.4 & \(\downarrow\) Hyperalgesia & \\  & & & \(\downarrow\) Allodynia & [48] \\  & & & & Amyotrophic lateral sclerosis \\ \hline GW405,833 & 8640 & 7.2 & \(\downarrow\) Hyperalgesia & [48] \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Selectivity of some SCs for CB1 and CB2 receptors, and their effects. On the base of their affinity and selectivity for receptors CB1 and CB2, they can exert both therapeutic and psychotropic effects, or mainly one of the two. Table 3 summarizes the selectivity of some SCs for CB1 and CB2, and their therapeutic effects. The following Figure 7 shows the chemical structures of compounds in Table 3 not previously reported in Figure 6.  
Methanandamide (AM-356) is a synthetically constructed stable chiral analog of anandamide. AM-356 acts on the cannabinoid receptors, and specifically on CB1-type receptors in the CNS found in mammals, fish, and certain invertebrates (e.g., Hydra), thus resulting also a psychoactive compound [68]. HU-210, as well as other SCs including L-759,656, HU-308, L-759,633, L-768,242 etc. are potent analgesic and anti-inflammatory compounds with many of the same effects as natural THC [44]. WIN 55,212-2 is an organic heterotricyclic SC. Particularly, it is the 5-methyl-3-(morpholin-4-ylmethyl)-2,3-dihydro [1,4]oxazine [2,3,4-hi]indole substituted at position 6 by a 1-naphthylcarbonyl group. It has a role as an analgesic, and neuroprotective agent, as well as an apoptosis inhibitor [69]. JWH-133 is a \(\Delta^{9}\)-tetrahydrocannabinol lacking the hydroxy group and having a 1,1-dimethylbutyl group at position 3 in place of the pentyl group. It acts as potent and highly selective CB2 receptor agonist, thus exerting antineoplastic effects, and working as a vasodilator and an anti-inflammatory agent, as an apoptosis inhibitor, as well as an analgesic molecule [70]. \(\Delta^{11}\)-THC, also known as exo-tetrahydrocannabinol, is a synthetic isomer of tetrahydrocannabinol, developed in the 1970s. It can be synthesized from \(\Delta^{8}\)-THC by several different routes, and only the (6 aR, 10 aR) enantiomer is known. In animal studies in mice, it was found to exert the same effect of \(\Delta^{9}\)-THC with around 1/4 its potency. It has been identified as a component of \"vaping liquids\" sold for use in humans [71].