## 2 Phytocannabinoids (PCs), Endocannabinoids (ECs) and Synthetic Cannabinoids (SCs)  
### Phytocannabinoids (PCs) and Endocannabinoids (ECs)  
Generally, the term 'cannabinoids' refers to a heterogeneous family of compounds that exhibit activity upon particular human cannabinoid receptors, namely CB1 and CB2 [41; 42]. They encompass the natural compounds present in the _Cannabis_ plants, lipid mediators called ECs naturally produced by human cells, as well as by all vertebrates on planet Earth, and the synthetic analogs of both groups designed by scientist, called SCs [42]. Natural cannabinoids from _Cannabis_ are more specifically called PCs referring to their original plant source, differently from ECs which are produced from human cells [43; 44]. PCs and ECs could include compounds structurally very different both between the two families and inside the same class, as shown in Figures 2 and 3, which report the structure of the most relevant PCs and ECs, respectively. Both PCs and ECs exert their effects by interacting with CB1 and CB2 receptors, found throughout the human body, and whose locations have been listed in Table 2. We have constructed Table 2 using the valuable information contained in the relevant work by [PERSON] et al. [45]. Figure 2: Chemical structure of the main PCs found in _C. sativa_ acting on CB1 and/or CB2 receptors. The activation of CB1 receptor or the concurrent activation of both receptors by ECs or PCs leads to both psychotropic, undesired effects and therapeutic outcomes. Exactly, while mind alteration, psychotropic effects, cardiovascular adverse events can occur, analgesic, sedative, antidepressant, anti-inflammatory, anti-anorexia, anti-emetic, anticancer and antibacterial desirable effects can also arise. As an example, the FDA-approved drug formulations containing the synthetic versions of A9-THC namely dronehold (marketed as Marinol(r) or Syndros(r)) or nabilome (marketed as Cesamet(tm)), as well as the extracted THC (marketed as Sativex(r)), possess affinity for both CB1 and CB2 [48]. Clinically, they are primarily used to treat the chemotherapy-induced nausea, to enhance appetite in cachexia AIDS-patients, and to alleviate the spasticity and pain associated with multiple sclerosis [30]. Unfortunately, evidence of undesired psychotropic and cardiovascular adverse effects strongly limits the therapeutic efficacy of such medicines [49]. Otherwise, the selective activation of CB2 receptors, occurring for example by CBG or CBD, could provide therapeutic effects, such as immuno-modulatory properties, anti-inflammatory, anti-emetic, and anti-anorexic effects without exerting the psychotropic actions deriving from the CB1 activation. In addition, the potent analgesic effects, associated with the activation of CB2, could be helpful in alleviating chronic widespread musculoskeletal pain (CWP) disorders, such as fibromyalgia syndrome [50]. Also, the selective activation of CB2 receptors could enhance severe human diseases as osteoporosis, atherosclerosis, cancer, chronic liver injuries and neurodegeneration [48]. Collectively, CB1 and CB2 receptors together with ECs make part of the so-called EC system (ECS), which was discovered in the 1990's by scientists researching cannabinoids, which includes also several enzymes involved