Scientists have identified several cannabinoid compounds that could potentially treat colorectal cancer.
A team at Pennsylvania State University College of Medicine in Hershey tested hundreds of cannabinoids on various types of human colorectal cancer cells in the laboratory.
Of these, 10 synthetic cannabinoids showed the ability to stop cancer cell growth. The well-known cannabis compounds tetrahydrocannabinol (THC) and cannabidiol (CBD) showed negligible ability to do the same.
The researchers see their findings as a starting point for further studies to better understand the anticancer effects that they observed, and to evaluate the compounds' potential for drug development.
They report their results in a paper that features in the journal Cannabis and Cannabinoid Research.
"Now that we've identified the compounds that we think have this activity," says senior study author Prof. Kent E. Vrana, who is chair of the Department of Pharmacology, "we can take these compounds and start trying to alter them to make them more potent against cancer cells."
"And then, eventually, we can explore the potential for using these compounds to develop drugs for treating cancer," he adds.
Colorectal cancer and cannabinoids
According to the World Cancer Research Fund, colorectal cancer is the "third most common cancer worldwide."
This is also the case in the United States, where a national surveillance program has estimated that colorectal cancer accounted for 8.1 percent of all new cancer incidences in 2018.
For several decades, overall rates of colorectal cancer diagnoses and deaths have been falling steadily in the U.S. Experts attribute this largely to changes in risk factors, more widespread screening, and better treatments.
However, this overall decline masks an opposite trend in that rates and deaths to colorectal cancer are rising among those of 50 years of age and under. The reasons for this remain unclear, although some suggest that obesity, changes in diet, and an increase in sedentary lifestyles may be involved.
Cannabinoids is a term that scientists use to refer to a large group of compounds that mostly exert their effect through cannabinoid receptors.
A receptor is a signal-receiving protein that sits on or inside cells and can alter cell behavior when it binds to a molecule that matches its affinity.
There are three main categories of cannabinoids. Phytocannabinoids are those that occur naturally in the cannabis, or marijuana, plant; endocannabinoids are those that arise within the body; while synthetic cannabinoids are those that scientists create in the laboratory.
However, more recently, scientists have shown growing interest in the potential anticancer effects of cannabinoids.
Study focused on synthetic cannabinoids
For the recent study, the researchers chose to investigate synthetic cannabinoids. From a "library of 370 molecules," they identified 10 synthetic cannabinoids that "inhibited cell viability" in seven types of colorectal cancer cells that came from human tumors.
Prof. Vrana explains that cancer can arise in cells in several different ways. "Each of the seven cells we tested," he says, "had a different cause or mutation that led to the cancer, even though they were all colon cells."
To screen the library of candidates, he and his team first cultured the cancer cells for 8 hours and then treated them with one of the compounds for another 48 hours.
If a compound showed signs of being able to reduce viability in one type of colorectal cancer cell, the researchers then tested it on the six other types.
After further tests and analyses, they whittled the number down to 10 compounds.
"Here, we demonstrated that 10 synthetic compounds are highly efficacious and moderately potent for reducing the viability of seven [colorectal cancer] cell lines," note the authors.
For the sake of comparison, they also ran tests on the two well-known phytocannabinoids THC and CBD. However, these showed a negligible ability to limit colorectal cancer cell viability.
The 10 compounds belong to three different classes of synthetic cannabinoid. The classes have many similarities, but they also have some small differences.
Prof. Vrana says there is a need for further research to understand better how the compounds work, and how to make them more potent and effective against colorectal cancer.
"We know how one of them works," Prof. Vrana notes," "which is by inhibiting the division of cells in general."
"We also found that the most potent and effective compounds don't seem to work through traditional marijuana receptors, although we're not sure of the exact mechanism yet."
Prof. Kent E. Vrana