# Antitumor Effects of _Cannabis sativa_ Bioactive Compounds on Colorectal Carcinogenesis
## 2 Bioactive Compounds of _Cannabis sativa_
### Cannabinoids  
Cannabinoids are a type of terpenophenolic compounds with a C\({}_{21}\) backbone [22]. The diversity of chemical structures of phytocannabinoids is mainly due to the differences between the isoprenyl groups, the side chain and the rescorinyl core [23]. Cannabinoids, according to their chemical structure, can be classified into 11 different classes: cannabigerol (CBG), cannabidiol (CBD), cannabichromene (CBC), \(\Delta^{9}\)-THC, \(\Delta^{8}\)-THC, cannabicyclol (CBL), cannabinol (CBN), cannabinodiol (CBND), cannabielsoin (CBE), cannabitriol (CBT), and miscellaneous-type cannabinoids [22; 24].  
Most cannabinoids originate from cannabigerolic acid (CBGA), as revealed in Figure 1. Its biosynthesis occurs with the production of CBGA from the alkylation of olivetolic acid with geranyl pyrophosphate (GPP). The primary cannabinoids, cannabichromenic acid (CBCA), cannabidiolic acid (CBDA), and \(\Delta^{9}\)-tetrahydrocannabinolic acid (\(\Delta^{9}\)-THCA), are synthesized in acid form by the enzymes CBCA synthase, CBDA synthase, and THCA synthase. Decarboxylation then converts the acidic forms of cannabinoids into neutral forms (THC, CBD, and CBC), which are recognized for having higher pharmacological potential [2; 25; 26; 27]. This conversion typically occurs naturally as the plant matures and dries, or because of heat exposure during processing or cooking [28].  
The phytocannabinoids are essentially produced in glandular trichomes, mainly in female infloresences. _C. sativa_ mostly syntheries cannabinoids of the alkyl type, characterized by a pentyl (C\({}_{5}\)) side chain and an isoprenyl (C\({}_{10}\)) monoterpene component. In general, \(\Delta^{9}\)-THC and CBD are the prevalent components of this plant and, based on the proportion of these two, three _C. sativa_ chemotypes are known: (i) drug type, with predominant \(\Delta^{9}\)-THC; (ii) intermediate type, with similar amounts of both cannabinoids; and (iii) fiber type, with predominant CBD. CBGA, CBDA, and their decarboxylated derivatives are the main cannabinoids found in the fiber type [20].  
Naturally, the quality and composition of _C. sativa_ extracts vary among the _C. sativa_ chemotypes. These are also highly dependent on other factors, including the extraction techniques employed. As an example, according to the study by [PERSON] et al. [29], a methanolic soxhlet extraction, which requires higher temperatures than ultrasound-assisted extraction (UAE), supercritical fluid extraction CO\({}_{2}\) (SFE-CO\({}_{2}\)), and ethanolic maceration, provided a higher quantity of decarboxylated cannabinoids in the final extract, i.e., in neutral form. In turn, the use of UAE, SFE-CO\({}_{2}\), and maceration improved the levels of  
Figure 1: Biosynthesis of cannabinoids in _Cannabis_. CBC, cannabichromene; CBCA, cannabichromenic acid; CBD, cannabidiol; CBDA, cannabidiolic acid; CBGA, cannabigerolic acid; \(\Delta^{9}\)-THCA, \(\Delta^{9}\)-tetrahydrocannabinolic acid; \(\Delta^{9}\)-THC, \(\Delta^{9}\)-tetrahydrocannabinol.  
acid forms of cannabinoids in the extracts. In this sense, efforts must be made to optimize the extraction procedure, keeping in mind the desired target compositions [30].  
Note that contrarily to \(\Delta^{9}\)-THC, CBD is psychotropically inactive and is of current interest due to its antiepileptic, antioxidant, and anti-inflammatory properties, being useful in neuropsychiatric disorders, and the attenuation of THC's negative effects [31]. The main pharmacological effects of the major cannabinoids are summarized in Table 1.