# _Cannabis sativa_ L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment
## 3 Chemical Composition
### Phenolic Compounds  
Phenolics, including flavonoids, lignans, and stilbenes, are yet another group of compounds found in _Cannabis_[42]. Phenolic compounds are synthesized from phenylalanine through the cytoplasmic phenylpropanol pathway. This precursor is phenylalanine, which can be transformed into esters, lignans, lignans, flavonoids, stilbenes, and coumarins. These compounds are formed mostly from tyramine and esters of coenzyme A with coumaric acid (p-coumaroyl-CoA), caffeic acid (caffeoyl-CoA), and coniferic acid (coniferyl-CoA). The course of the synthesis of flavonoids is shown in the diagram (Figure 7) [42]. Twenty-six flavonoids, which mainly represent flavonoids and flavones, were isolated from _Cannabis_ sp., including apigenin, luteolin, kaempfer, vitexin, isovitexin, orientin, and quercetin [80; 81]. There is a considerable variation in the content of flavonoids between different varieties of _C. sativa_ L., as well as between the individual parts of this plant. Their presence has been confirmed in flowers, twigs, leaves, and pollen. Methylated isoprenoid flavones, cannflavin A and cannflavin B, first isolated in 1980 by [PERSON] and [PERSON] were also reported (Figure 8) [82]. The biological activity of cannflavin's seems to be connected with their structure: a prenyl side chain--a geranyl (C10--cannflavin A) or a dimethylallyl (C5--cannflavin B) group, which is attached to the six position of the flavone A-ring--and modification at the 3' flavone B-ring position with a methoxy group, which elevates the lipophilicity and results in a higher permeability through biological membranes [83; 84; 85]. In 2008, another compound from this rare group--cannflavin C  
Figure 7: Diagram of the biosynthesis of phenolic compounds [42]. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Cannabinoids** & **Terpenes** & **Use** \\ \hline CBD & limonene, linalool, pinene & acne treatments \\ CBG & pinene & antiseptics \\ CBD & limonene, linalool & anxiety disorders \\ Extract CBD/THC 1:1 & caryophyllene, linalool, myrcene & sleep disorders \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Examples of the use of combinations of cannabinoids with terpenes [64]. CBG: cannabinoid. was isolated [81]. It seems that the germination process elevates the production of the mentioned cannflavins [80]. _Cannabis_ sp. flavonoids have antibacterial, anti-inflammatory, antiproliferative, and neuroprotective properties. Flavonoids can affect the pharmacokinetics of \(\Delta^{9}\)-tetrahydroocannabinol [80]. Besides, apigenin has estrogen and anxiolytic properties. Cannflavins A and B, due to the inhibition of 5-lipoxygenase and prostaglandin E\({}_{2}\), show anti-inflammatory effects [42]. Moreover, cannflavin B exhibits antimicrobial and antileishman activity [80]. Two groups of lignans were detected in _C. sativa_ L.: lignanamides and phenolic amides. They occur in the roots, fruits, and seeds of the plant [81]. The lignanamides found in _Cannabis_ include cannabisins and grossamide. For the first time, cannabisin A was detected from _Cannabis sativa_ in 1991 [86]. Later, more and more cannabisins were identified. Cannabis M, N, and O were identified quite recently, in 2015 [87]. They have antioxidant, anti-inflammatory, and neuroprotective properties [87; 88]. Cannabis D is present in _Cannabis_ leaves, and its amount increases strongly with exposure to UV light. Significant levels of lignans such as syringaresinol, pinoresinol, lariciresinol, and secoisolariciresinol were determined in the hydrophilic extract obtained from _Cannabis_ seeds. However, it was found that the total amount of lignans in _Cannabis_ seeds is about 20 times lower than in flax seeds and is only 32 mg per 100 g of dry weight [89]. Moreover, the content in the seed shell is only 1% of the lignans content in the whole seed. Lignans have antiviral, antioxidant, antidiabetic, and anticancer properties and can be used in the treatment of obesity [90].