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Study: CB1 ECS Receptor Plays Key Role in Colon Cancer

Updated: Apr 13, 2023

This article is brought to you by the new Higher Learning LV Cannabis for Cancer seminar.

 

Welcome to Higher Learning LV's Study Summary series. This series reviews and summarizes peer-reviewed research studies and was developed specifically for cannabis industry professionals. These study summaries provide easily digested quick reads for a variety of important issues regarding the commerce and chemistry of legal cannabis.

A 2008 preclinical study entitled "Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth" that was published in the journal Cancer Research explored the potential role played by the human endocannabinoid system (ECS) in fighting colorectal cancer.


"Cannabinoids are currently used to treat chemotherapy- or radiotherapy-induced nausea and vomiting, as well as for pain relief, insomnia relief, mood elevation, and appetite stimulation," wrote the scientists. "Medicinal use of these compounds is also thought to be beneficial for digestive disorders such as diarrhea and Crohn's disease," they added.


The Study

The study echoed how the cannabinoids produced by cannabis and hemp (such as CBD and THC) act very similarly to the endocannabinoids produced by the human ECS, including anandamide and 2-AG. "Plant-derived cannabinoids and their derivatives exert a wide variety of biological effects by mimicking endogenous compounds (endocannabinoids), which primarily activate two cannabinoid-specific G-protein–coupled receptors, CB1 and CB2," reported the study.


The study echoed how the cannabinoids produced by cannabis and hemp (such as CBD and THC) act very similarly to the endocannabinoids produced by the human ECS, including anandamide and 2-AG.

The scientists noted that previous studies suggest "that cannabinoids exert potential antitumor effects on a wide spectrum of human tumor cell lines" and emphasized the anti-inflammatory support provided by cannabinoids.

"Because chronic inflammation is a known risk factor for [colorectal cancers], the aim of the present study was to determine the role of cannabinoid receptors in a mouse model of colon cancer and the mechanism of the receptor action," stated the researchers.


More specifically, "to understand the role of endocannabinoid signaling in [colorectal cancers]," the scientists examined "the expression pattern of CB1 and CB2 in human grade 2 to 3 colon carcinomas."


The Results

The study reported that the gastrointestinal tracts of humans, mice, and rats "produce two major endocannabinoids, anandamide and 2-arachidonoyl-glycerol [2-AG]." It noted that patients with colorectal cancers feature cancer cells that produce two to three times more anandamide and 2-AG "than do the neighboring normal [cells]."


The research reported that CB1 receptors in the ECS may play a critical role in supporting the body's ability to maintain health and, more specifically, it's potential to fight cancer.

The research reported that CB1 receptors in the ECS may play a critical role in supporting the body's ability to maintain health and, more specifically, it's potential to fight cancer.

"CB1 [receptors] provide intrinsic protection against colonic inflammation," reported the study. It found that "endocannabinoid signaling is important in regulating gastrointestinal motility, secretion, and neurotransmitter release," all of which are necessary for proper gastrointestinal health.


The study employed quantitative real-time analysis that "revealed greatly reduced expression of CB1 [receptors] in 18 of 19 cancer specimens" when compared to normal cells. "In contrast, no recognizable pattern of CB2 [receptor] expression was found in tumor tissues or in the colorectal cancer cell lines examined," reported the scientists.


The study employed quantitative real-time analysis that "revealed greatly reduced expression of CB1 [receptors] in 18 of 19 cancer specimens."

The research reported that when patients suffer a "loss of CB1 expression" in their ECS, it "could be associated with [colorectal cancer] progression."


Conclusions

The study noted that previous research investigations have revealed the role of CB1 ECS receptors in fighting cancer, but that these preclinical studies did not feature living creatures (instead, they worked with cell cultures and employed other techniques). "Our results further show that the CB1 receptor mediates the antitumor effects of endocannabinoids in vivo [in living creatures]," reported the study.

It suggested that colorectal cancer patients may not benefit from an increase in their endocannabinoid levels due to unresponsive (down-regulated) CB1 receptors in their ECS and that this "may represent a general mechanism in other cancer types and may provide a new therapeutic strategy for treatment and/or prevention of colorectal cancers."


The researchers theorized that unresponsive CB1 receptors are associated with disease states and neurodegenerative diseases beyond cancer, "including Huntington's disease, Alzheimer's disease, and multiple sclerosis." However, they also stressed the need for additional research into the role of CB1 receptors—and the ECS overall—in fighting various cancers and other conditions. "Further investigation is required for examining whether CB1 expression is reduced in other cancer types as well," concluded the study's authors.


"We provide in vivo evidence showing that endocannabinoid signaling via CB1 [receptors] plays a key role in regulating intestinal tumor growth," summarized the study.

The scientists emphasized that the anticancer efficacy of cannabinoids involves more than one mechanism or biochemical pathway. "In addition to stimulating apoptosis*, cannabinoids have been shown to have antiproliferative effects on colorectal cells," they reported.

Importantly, the researchers also revealed that "some biological effects of cannabinoids are known to be independent of CB receptor binding," hinting at the complexity of the interaction of cannabinoids within the human endocannabinoid system and the significant gaps of understanding with which modern researchers and medical professionals must deal.


"Endocannabinoid signaling via CB1 [receptors] plays a key role in regulating intestinal tumor growth," summarized the study.

"We provide in vivo evidence showing that endocannabinoid signaling via CB1 [receptors] plays a key role in regulating intestinal tumor growth," summarized the study. "Our results may provide a rationale for the development of CB1 agonists that do not cross the blood-brain barrier [and, thus, cause no psychoactivity] for cancer prevention," concluded the scientists.


*Apoptosis is a genetically programmed mechanism by which certain cells, including cancers, kill themselves via what is basically cellular suicide. Other research studies indicate that certain cannabinoids and terpenes play a role in apoptosis and that this is one of the chief mechanisms by which these phytomolecules may act as effective therapeutic agents against cancer.


View the original study.


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