# Phytocannabinoids Biosynthesis in Angiosperms, Fungi, and Liverworts and Their Versatile Role
## 6 Phytocannabinoids and Their Derivative Role and Bioactivity in Humans and Animals
### Cannabinoid Receptors in Humans and Their Role
G-protein-coupled receptors (GPR), such as GPR18 and GPR55, serve as potent phyto-cannabinoid receptors. GPR18 is a \"deorphanized\" receptor present in cells and tissues of the thymus, spleen, small intestine, lymph nodes, leukocytes, and gametes [92; 93; 94; 95]. Phytocannabinoids (e.g., \(\Delta^{9}\)-THC) are agonists to GPR18. It plays a potent role in signalizing toxin-sensitive G-protein, Akt, PI3K, and p42/44 mitogen-activated protein kinase [96; 97]. Additionally, cannabinoid (e.g., \(\Delta^{9}\)-THC) induces \(\beta\)-arrestin recruitment in the cells which are transfected with GPR18 [86; 95]. GPR55 is the important \"deorphanized\" metabotropic receptor that interacts with several active phytocannabinoids; it is present in the central nervous system (CNS), adipose tissues, adrenal gland, immune cells, small intestine, osteoblasts and osteoclast [98; 99]. GPR55 displays a low sequence with both CB\({}_{1}\)R and CB\({}_{2}\)R (about 15%); GPRs interact with G\(\alpha\)12 or G\(\alpha\)13, which results in activation of several pathways such as Rho-associated protein kinase, Ras homolog gene family member A (RhoA), p38, MAPK/ERK pathways [91; 100]. Some phytocannabinoids potently activate GPR5. Moreover, GPR55 is the most complex CBR. The same ligand acts as an agonist, antagonist, or neutral; it also possesses the allosteric modulator site [86; 87]. Phytocannabinoids serve as weak and partial agonists on the GPR55, but via the help of some cannabinoids (CBD, cannabitivarine, CBDV), they inhibit lysophosphatidyllinked GPR55 activation. Thus, GPR55, along with cannabinoids, can participate in curing cancer cells, obesity, inflammation, neuropathic pain, osteoporosis, and neuromodulation. Transient receptor potential (TRP) superfamily channels have 27 polymodal sensor cation channels classified into six broad types in humans [101]. Among these six families, four groups interact with cannabinoids and other derivatives. Thus, these participate in boosting the immune system, with analgesia (pain reliever), and nociception (processing of sensory nervous system); they also modulate inflammations and pain sensations [102; 103; 104]. Phytocannabinoids exerts strong therapeutic potential in humans assessed by the meta-analysis of several clinical trials; it possesses a strong effect on health conditions such as nausea, vomiting, insomnia (sleeping disorder), depression, anxiety, paraplegia (paralyzes in a lower limb due to spinal cord injury), psychosis (emotional metal disorder), appetite stimulation in several syndromes [86]. Additionally, cannabinoids play a significant role in ailments of human diseases and syndromes such as Tourette syndrome (nervous system disorder such as continuous movements), AIDS, and treating intraocular pressure of the eye in glaucoma [105]. The endocannabinoid system (internal lipid retrograde neurotransmitters which bind on CBR) along with phytocannabinoid is involved in modulating pharmacological, physiological, biological, and cognitive processes [106]. Due to the limited space, in this review, we only name diseases and ailments cured by phytocannabinoids that are liver encephalopathy, hepatic disease, asthma, respiratory tract changes, bronchospasm, bone remodeling and metabolism, osteoarthritis, and osteoporosis. Phytocannabinoids may also be used to treat diseases related to CNS such as brain trauma, stroke, brain aging, neuroinflammation, and neurodegeneration. Additionally, they have served as an anti-solid depressant to cure patients with suicidal tendencies; apart from all this, they are a strong pain reliever and immunomododulator. Phytocannabinoids are also given to pregnant women to avoid miscarriage and preimplantation embryo development [86; 105; 107]. Phytocannabinoids have several medicinal properties in curing diseases and disorders and assist as an important template for chemists to form novel and synthetic medicine [108]. Several investigations display the potential of synthetic cannabinoids in human ailments.