# Antitumor Effects of _Cannabis sativa_ Bioactive Compounds on Colorectal Carcinogenesis
## 3 Bioactive Compounds in the Prevention and Treatment of Colorectal Cancer
### Effects of Cannabinoids in CRC-Associated Mechanisms
#### 3.1.2 \(\upDelta^{9}\)-Thc  
THC has also been reported to have good outcomes in inhibiting cell viability on CRC cells, namely, SW480, HCT-15, HT-29, and HCA7 [52; 64]. In HT-29 cells, THC suppressed cell viability more than CB83 (a synthetic cannabinoid) after 24 h of treatment at 30 \(\upmu\)M [52]. Additionally, [PERSON] and coworkers reported that \(\upDelta^{9}\)-THC and \(\upDelta^{8}\)-THC were more toxic to polyp-derived cells than other cannabinoids, namely, CBD, CBC, CBDV, THCA, CBG, and other minor cannabinoids [65]. Furthermore, THC at 30 \(\upmu\)M was shown to trigger significant inhibition of proliferation at 24 h (70.9 \(\pm\) 5.59, \(p\) < 0.01) in HT-29 CRC cells, compared to untreated cells [52].  
The induction of apoptosis by THC through the activation of the CB1 receptor in CRC cells was first reported in 2007 by [PERSON] et al. [64]. The authors suggested that apoptosis was induced by the activation of the B-cell lymphoma-2 (Bcl-2) family member BAD protein dependent on the CB1-mediated Ras-mitogen-activated protein kinase and PI3K/Akt pathway inhibition. In reality, the inhibition of ERK and Akt activity by THC was complemented by activation of the proapoptotic BAD. Additionally, THC increased the simultaneous cleavage of the caspase-3 substrate PARP. Through staining with 4',6-diamidino-2-phenylindole, morphological changes such as chromatin condensation and micronucleleation were seen in cells treated with THC. [PERSON] et al. [52] supported the evidence that THC acts through the CB1 receptor in inducing cytotoxicity in HT29 cells.  
In addition to the previous effects, THC was also claimed to exhibit anti-inflammatory and antimutomal potential in AOM/dextran sodium sulfate (DSS)-induced female C57 BL/6 mice [48]. After treatment with THC (10 mg/kg body weight), the animals' colons had a significant reduction in the severity of inflammation and tumor induction, as indicated by hematoxylin and eosin staining. Furthermore, this cannabinoid caused a reduction in IL-22 produced mainly by intra-epithelial cells, a cytokine that plays an important role in the severity of inflammation-induced colon cancer.  
Optimizing the delivery method can improve the efficacy of THC treatment for CRC owing to its lipophilicity, tar-like viscosity, and instability. In fact, [PERSON] et al. suggested an alternative method of THC delivery. The oil-in-water emulsion solvent evaporation method used by the authors to encapsulate THC into biodegradable microspheres revealed its ability to prevent cancer cell proliferation in CACO-2 cells [66].  
Due to THC's psychoactive effects, clinical research has linked certain negative effects with its use, including dysphoria, depersonalization, anxiety, panic attacks, and para-noia [67]. Long-term use and high doses have been associated with most of these negative consequences. According to studies on cannabinoid effects, some of the harmful effects of THC may be mitigated by CBD. However, the results are not always consistent [68]. More research is needed to determine if THC can be used in combination with other treatments, such as chemotherapy, to improve outcomes. Studies should also evaluate the potential long-term effects of THC use in patients and/or animals with CRC.