# Antitumor Effects of _Cannabis sativa_ Bioactive Compounds on Colorectal Carcinogenesis
## 1 Introduction  
Cannabis is one of humanity's oldest plants, yet it has also been a topic of discussion throughout history [1]. This plant is psychotropic and includes about 500 distinct chemical components, the most important of which are cannabinoids. The _Cannabis indica_ [PERSON], _Cannabis ruderalis_ [PERSON], and _Cannabis sativa_ [PERSON] are the species with the most psychotropic secondary metabolites. _C. ruderalis_ yields smaller amounts of \(\Delta^{9}\)-tetrahydrocannabinol (\(\Delta^{9}\)-THC) and is less used in medicine, while _C. indica_ is typically employed as a sedative, and _C. sativa_ as a psychoactive [2]. Among them, _C. sativa_ is the most widely cultivated and exploited for a variety of purposes [3].  
Cannabis for medicinal uses has recently been legalized in many countries. Plant material and extracts can be used to alleviate chronic pain and muscle spasms, reduce nausea during chemotherapy, improve appetite in HIV/AIDS patients, improve sleep, and reduce tics in Tourette's syndrome patients. Moreover, it can be used in extreme cases of anorexia, arthritis, glaucoma, and inflammatory bowel disease [4]. The bulk of medicinal compounds is found in feminine inflorescences, and medicinal properties are commonly attributed to cannabinoids, although other bioactive substances, including terpenes, may also contribute to the health effects of cannabis [5]. According to the entourage effect theory, the medicinal benefits of cannabis are increased when all the plant's constituents, such as terpenes, flavonoids, and cannabinoids, are present and interact with each other. Some researchers believe that the entourage effect may be especially important when it comes tothe potential use of cannabis for cancer treatment [6]. In fact, cannabinoids and terpen are known to have a whole range of potential health benefits, ranging from pain relief [7; 8] to anti-inflammatory properties [9; 10]. Thus, the high interest in these compounds is related to their numerous pharmacological properties. Regardless, this topic is far from being well understood.  
Colorectal cancer (CRC) is one of the cancers with the highest incidence and mortality worldwide, due to the lack of early diagnosis methods and effective treatments. Cannabinoids are known to interact with the intestinal endocannabinoid system (ECS), which expresses CB1 and CB2 receptors, other G-protein-coupled receptors, endogenous ligands, and degrading enzymes [11]. It has been suggested that _C. sativa_ can exert anticarcinogenic effects, through antiproliferative, anti-inflammatory, pro-apoptotic, antiangiogenic, and other mechanisms, including in CRC [12; 13]. However, the research on the use of _C. sativa_ bioactive compounds for the treatment of this cancer is still limited and inconclusive.  
On the other hand, it is important to consider that cannabis consumption can also have adverse impacts on health, normally triggered by THC. These effects may include fatigue, tachycardia, nausea, dizziness, dry mouth, altered mood and behavior, psychomotor impairment, and visual and auditory hallucinations [14; 15]. Furthermore, the long-term use of medicinal cannabis may increase the risk of substance use disorder and psychiatric comorbidities. It is also vital to remember that marijuana is still controlled in several countries where using it is prohibited [4].  
This review summarizes the current knowledge regarding the potential benefits of cannabinoids, terpen, and their mixtures from _C. sativa_ for the prevention and treatment of CRC, focusing on their effects on apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. While the bioactivity of cannabinoids in CRC has been reviewed before [16; 17; 18], this work highlights the importance of understanding the effect of terpen and their synergistic effects with cannabinoids to fully elucidate their mechanisms of action and safety.