# Phytocannabinoids Biosynthesis in Angiosperms, Fungi, and Liverworts and Their Versatile Role
## 6 Phytocannabinoids and Their Derivative Role and Bioactivity in Humans and Animals
### Bioactivity of Phytocannabinoids
#### 6.2.1 Neutral Cannabinoids  
In humans, phytocannabinoids play a potent role in signal transduction. They show crucial interaction with the G-protein coupled cannabinoid receptors (GPCRs such as CB\({}_{1}\)R and CB\({}_{2}\)R), peroxisome proliferator-activated receptor \(\gamma\) (PPAR\(\gamma\)), and TRP ion channel. CB\({}_{1}\)R is the most abundant GPCR located in CNS, whereas CB\({}_{2}\)R is found in immune cells and tissues. Thus, cannabinoids play a crucial role in signaling, immune, and CNS proper functioning [72; 74]. In humans, \(\Delta^{9}\)-THC displays pleiotropic effects such as analgesic (relieve pain), relaxation, pain tolerance, and dysphoria (anxiety disorder); thus this reveals \(\Delta^{9}\)-THC displays agonistic effects by the activation of CB\({}_{1}\)R of \(\beta\)-arrestin 2 recruitment and signaling; also \(\Delta^{9}\)-THC is the essential psychoactive (alters mood, behavior, feeling and thoughts by affecting CNS) bioactive constituent [73; 104]. \(\Delta^{9}\)-THC is found in the drug dronabinol (Marinol(r)), and the constituent of sesame oil plays potent antigenetic (prevents vomiting) for cancer patients receiving chemotherapy. Additionally, it also stimulates appetite in a patient with AIDS (acquired immunodeficiency syndrome); chronic administration of doses increases weight and appetite. \(\Delta^{9}\)-THC is also given to patients with insomnia and depression as it improves sleep. In humans, \(\Delta^{8}\)-THC decreases intraocular pressure (fluid pressure inside the eye) and exhibits antiglaucoma activity [76]. Phytocannabinoid CBG possesses non-psychotic activity that has a lower affinity for both CB\({}_{1}\)R and CB\({}_{2}\)R, several times lower than \(\Delta^{9}\)-THC. CBG has remarkable activity towards ligand-gated cation channels of superfamily TRP. CBG serves as an agonist of TRP type ankyrin 1 (TRPA1) and TRP type vanilloid 1 (TRPV1), whereas it acts as an antagonistic of TRP type melastatin 8 (TRPM8). \(\Delta^{9}\)-tetrahydrocamnabivarinic acid (\(\Delta^{9}\)-THCV) serves as a non-psychoactive that is antagonistic to CB\({}_{1}\)R. In particular, \(\Delta^{9}\)-THCV potentially acts against obesity-linked glucose intolerance. In humans, it acts as the potential phytocannabinoid for treating metabolic disorders, hepatosteatosis syndrome, and obesity. It also helps recover fasting plasma glucose and pancreatic \(\beta\) cell functioning. Additionally, \(\Delta^{9}\)-THCV reduces adiponectin and apolipoprotein [75].  
CBD plays a potent pharmacological role in humans by affecting CNS and some peripheral portions, as it is highly antagonistic to CB\({}_{1}\)R and CB\({}_{2}\)R. Additionally, CBD also acts as an essential allosteric modulator of receptor \(\mu\)-opioid (pain reliever), thus used to relieve pain [75]. In humans, doses in the range of 10 to 700 mg CBD are not toxic and are delivered to patients in the form of Epidiolex(r) with epilepsy treatment-resistant, interlinked with CDKL5 deficiency disorder and many other disorders and syndromes [80]. CBD does not act as a psychoactive compound and can be delivered in patients receiving pharmacotherapy. Furthermore, CBD reduces \(\Delta^{9}\)-THC-elicited psychotic disorders and decreases the deleterious effect of \(\Delta^{9}\)-THC on memory which is hippocampus-dependent. CBD acts as the potential cannabinoid to cure obesity, convulsive disorder, and rheumatoid arthritis. Furthermore, CBD also possesses antipsychotic, antianusea, and antianxiety properties [79].  
CBC acts as the non-psychotropic which does not interact with CB\({}_{1}\)R and CB\({}_{2}\)R [5; 78]. Additionally, CBC inhibits endocannabinoid inactivation and further activates TRPA1, which helps recover intestinal inflammation and has several protective roles [110; 111]. Additionally, CBC also possesses anti-inflammatory activity for curing lipopolysaccharide-enhanced edema. In particular, till 2021, no CBC study involves humans [112].