## 2 Phytocannabinoids (PCs), Endocannabinoids (ECs) and Synthetic Cannabinoids (SCs)
### Phytocannabinoids (PCs) and Endocannabinoids (ECs)
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Receptor Type** & **Location** & **Sublocation** & **Ref.** \\ \hline \multirow{4}{*}{CB1} & Central nervous system (CNS) & Hippocamp, cerebellum, basal ganglia, cortical regions & \\  & & Olfactory areas & \\ \cline{2-4}  & Peripheral nerve terminals & Eye, vascular endothelium, adipose tissue, lungs, liver & [46] \\  & Extra-neuronal sites & Spleen, kidneys, uterus, prostate, testis, stomach, placenta & \\  & & Skeletal, muscles & \\ \hline \multirow{4}{*}{CB2} & Peripheral immune & \multirow{2}{*}{Spleen, tonsils, thymus, lymph nodes} & \\  & system tissues & & \\ \cline{1-1} \cline{2-4}  & Peripheral immune & B cells, natural killer cells, monocytes, macrophages & \\ \cline{1-1}  & system cells & Neutrophphils, CD8+ T cells, CD4+ T cells & \\ \cline{1-1} \cline{2-4}  & & Cresbulum, olfactory tubercle, striatum & \\ \cline{1-1} \cline{2-4}  & & Thalamic nuclei (hippocampus and amygdala) & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Locations of CB1 and CB2 receptors in the human body. Figure 3: Chemical structure of the main ECs found in humans acting on CB1 and/or CB2 receptors. in producing and recycling ECs. In humans, ECs are naturally produced by cells within the body in response to external factors, like pain or temperature. As shown in Figure 3, among other molecules, ECs include the well-known compounds 2-arachidonoylglycerol (2-AG) and anandamide (ANA), as well as the less-known ECs like virodamine, and 2-arachidonoyl glycerol ether [51]. Particularly 2-AG and ANA activate both CB1 and CB2 receptors with affinity for CB1 higher than that for CB2 [48]. Collectively, the interaction between ECs and their corresponding receptors is pivotal in maintaining the body's internal balance or homeostasis. ECs regulate some very important aspects of human health, as depicted in Figure 4.  
Researchers suggest that ECs deficiencies could cause many refractory health conditions, such as depression, arthritis, fibromyalgia, and [PERSON]'s disease that could ameliorate upon treatments with _Cannabis_, due to the activation by PCs of the same receptors activated in normal conditions by ECs. In fact, as reported above, PCs specifically produced by _Cannabis_ plants and not by humans, when appropriately assumed can interact with CB1 and/or CB2 receptors triggering effects similar to those prompted by ECs, thus influencing the same aspects reported in Figure 4 and contributing to maintain or recover the body's internal balance or homeostasis [41]. Anyway, if abused, the psychotropic and undesired side effects of psychoactive PCs, such as THC and CBN may overwhelm the benefits. Figure 5 shows the chemical structure of two metabolites which form in the human body after _Cannabis_ consumption, of cannabicyclolic acid (CBLA), a degradative byproduct of cannabichromenic acid (CBCA), and of cannabicyclol (CBL) which is the product of decarboxylation of CBLA [53]. Particularly, CBL is a non-psychoactive cannabinoid, which could also derive by degradation of CBC through natural irradiation or under acid conditions [54]. Particularly, CBLA, like CBCA and CBC, is a minor cannabinoid found in low concentrations in the _Cannabis_ plant. It is not produced by _Cannabis_ directly, but it forms when CBCA degrades after exposure to ultraviolet (UV) light or heat. CBLA is an acidic cannabinoid, like THCA, CBCA and CBDA, which produces CBL, upon decarboxylation and release of CO\({}_{2}\). CBLA is not considered intoxicating, is often deemed non-psychoactive or non-psychotropic, and curiously, it does not interact with receptors CB1 and CB2. There is little research into the effects and potential therapeutic uses of CBLA and CBL. Anyway,  
Figure 4: Aspects of humans’ life regulated by the ECS, through the interaction of ECs with receptors CB1 and/or CB2, as reported in the relevant review by [PERSON] et al. [52].