Pot potential

Promising research suggests CBD could help beat back an aggressive cancer

Early-stage cell studies point to another way CBD could become medicine.

CBD is as trendy for dogs as it has been for humans. With the hype that touts the cannabinoid as a cure-all, it's easy to forget that CBD has serious medical clout.

According to new research, it now shows promise in combating one of the most serious medical issues for both people and pets: glioblastoma, a common and often-deadly form of brain cancer.

Gliomas are tumors that often occur in the brain or spinal cord, and begin in glial cells – "gluey" cells that, when functioning normally, surround neurons and help them function. It's estimated that gliomas make up about 30 percent of all brain tumors, and 80 percent of malignant tumors (which are the ones that are cancerous).

Gliomas can be extremely aggressive. The survival rate for patients with malignant brain tumors is about 36 percent according to the National Brain Tumor Society.

A study released Monday, based on results from human and canine cells, suggests that CBD could effectively be used alongside other cancer treatments because of its ability to disrupt how cancer cells function.

CBD can slow cancer growth because it causes the mitochondria in cancer cells to dysfunction, the study reports. Mitochondria is what allows the cells to produce energy, and keep living.

This study has not been published in a journal, but would have been presented at the 2020 Experimental Biology conference (it has been canceled due to the coronavirus).

Chase Gross is the study's first author and a student at Colorado State University's Doctor of Veterinary Medicine program. He suggests that these results may lead to improved cancer treatments for both humans and our pets, who also suffer from brain tumors as well.

"CBD has been zealously studied in cells for its anticancer properties over the last decade," Gross explains. "This could lead to new treatments that would help both people and dogs that have this very serious cancer."

For dogs, brain tumors are responsible for about 2 percent of deaths. They tend to appear in long-nosed dogs, like Golden Retrievers but are also common in Boston Terriers, French Bulldogs, Boxers, Doberman Pinschers, Scottish Terriers, and Old English Sheepdogs.

CBD is one of hundreds of active components of cannabis, but unlike THC it's not responsible for the high associated with marijuana. Tinnakorn jorruang/Shutterstock

Importantly, CBD cannot be used to treat cancer. This distinction is important: The CBD industry is rife with false or unproven claims about what it can actually do. The FDA is is "increasingly concerned" about cannabis products that falsely claim to shrink tumors or treat cancer.

Past studies have suggested that cannabinoids, like CBD, may have anti-tumor effects, but these are largely dependent on the type of cancer and the dosage in question. For glioblastoma, past research suggests that CBD can mess with various molecular pathways that tumors use to thrive.

Here, CBD is described as a "synergistic glioblastoma therapy option," meaning it could potentially be used in tangent, and boost, other forms of treatment.

Gross and his colleagues tested the effect of a pure CBD isolate and another form of CBD that had minimal amounts of THC and other cannabinoids. On its own, CBD was both cytotoxic (meaning it killed some cells), and stopped other cells from proliferating.

However, the concentrations of CBD needed to achieve those effects were "not pharmacologically possible" the authors write. Crucially, this study is an early step towards proving CBD's effectiveness.

Still, the team found that, even in lower concentrations, CBD was able to mess with mitochondria. Ultimately, they argue that CBD causes the mitochondria to release reactive oxygen species which can cause DNA damage or cell death.

It also appeared to create large, swollen vesicles inside the cell that were the precursors of a breakdown in the cell.

Taken together, this suggests CBD sets off the cancer cell's internal "self-destruct" functions (also called apoptosis or programmed cell death).

The swollen vesicles after they were treated with CBD. This swelling is a "hallmark" of cell death, the authors suggest. Chase Gross, Mando Ramirez, Colorado State University

Before this work can go any further, the team will need to scale up animal testing, likely, in dogs.

But these results, as Gross notes, may present a path forward. In 2020, an estimated 87,240 people may receive a brain tumor diagnosis. These results represent one of many ways scientists are searching for solutions beyond what we already have. While there is no cure for glioblastoma, there are treatment options. In the future, these might be paired with CBD.

Abstract: The use of cannabidiol (CBD), the major non-psychoactive compound derived from cannabis, as a nutraceutical in both human and veterinary medicine has increased steadily within the past ten years despite a lack of scientific evidence for its effectiveness. Of the cornucopia of ailments that CBD supposedly treats, epilepsy, pain, and cancer remain prominent areas of interest to scientists and the general public. In the world of cancer research, several publications have demonstrated that CBD is cytotoxic against breast, endometrial, glial, and blood cancers, and in all cases it appears that CBD triggers apoptosis through a cannabinoid receptor independent process. A recent publication suggests CBD causes cell death in leukemia cells via calcium dependent mitochondrial membrane disruption, leading to activation of intrinsic apoptosis. Other receptors, such as TRPV1, and pathways, such as autophagy, have been implicated in CBD-induced cell death but the molecular details remain elusive. Because of their remarkable similarities, from a comparative oncology perspective, canine and human gliomas are of particular interest. Regardless of species, gliomas are aggressive tumors that are notoriously challenging to treat, given their resistance to multimodal treatment, thus creating a need for more effective therapeutics. We sought to characterize the mechanism of CBD-induced cell death in both human and canine glioma cells. We show that CBD by itself is cytotoxic, anti-proliferative, and anti-migratory but at concentrations which may not be pharmacologically attainable. Using resazurin and the IncuCyte live cell imaging platform, we show that metabolic-based assays artificially increase cell line sensitivity to CBD compared to the IncuCyte, suggesting that non-cytotoxic concentrations of CBD perturb mitochondrial function. Furthermore, we show that CBD treatment results in the formation of large cellular structures whose existence are RIPK3-dependent. After treatment with a variety of cell death inhibitors, we demonstrate that CBD-induced cell death occurs via apoptosis; a classically necroptotic protein, RIPK3, also appears to be involved. Lastly, by combining CBD with the autophagy inhibitor hydroxychloroquine (HCQ) we show that sensitivity to CBD increases with HCQ treatment in canine cells, which suggests involvement of the autophagy pathway for mediating CBD-induced cell death. These data demonstrate that human and canine glioma cells respond similarly to CBD, indicate a non-canonical function of RIPK3, and support the involvement of autophagy in CBD-induced cell death.

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