Dee Mani is Amazon's best-selling author, cannabis & natural health advocate
Dee Mani is Amazon's best-selling author, cannabis & natural health advocate
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It’s no secret that many cancer patients are using cannabis to help manage pain, fatigue, nausea, and other direct effects of chemotherapy. Less known is that extensive preclinical research shows that plant cannabinoids — most notably, tetrahydrocannabinol (THC) and cannabidiol (CBD) – produce antitumor responses in various animal models of cancer.
Most of this preclinical research has examined the anticancer activity of pure compounds, mainly THC isolates. But medical cannabis patients aren’t using pure, single-molecule THC to battle cancer. Instead, they are consuming whole-plant cannabis oil extracts that include hundreds of compounds, many of which also have therapeutic properties. These artisanal cannabis oil preparations known as FECO, are available in licensed dispensaries in the USA, where medical cannabis is legal, and elsewhere via the black market.
However, few rigorous studies have analysed the effects of whole-plant cannabis extracts. So a team of Spanish researchers, led by Cristina Sanchez at Complutense University in Madrid, decided to compare the efficacy of pure THC isolates and THC-rich oil extracts in a series of preclinical experiments focused on breast cancer. The researchers also investigated the effects of pure THC and an artisanal THC-rich oil formulation when combined with standard chemotherapy drugs.
Their findings were reported in a 2018 article – “Appraising the ‘Entourage Effect’: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer”, – which was published in the journal Biochemical Pharmacology.
The phrase “entourage effect” in this context refers to the FECO synergistic interplay between numerous cannabis compounds – cannabinoids, terpenes and flavonoids – that impart a therapeutic impact more significant than the sum of the plant’s components.
One in eight women is estimated to develop breast cancer (these statistics are more than likely much higher now in today's society). Unfortunately, breast cancer is tricky to treat because few biomarkers signal when someone has the disease, and many patients show or develop resistance to current conventional therapies. Moreover, several specific types of breast cancer respond poorly to modern toxic treatment. These difficulties underscore the importance of exploring new treatments for breast cancer. Although we do know the pharmaceutical/medical industry will never be able to recommend totally holistic healing, whilst the 1939 Cancer Act is still in place.
Two biomarkers frequently used to diagnose breast cancer are hormonal receptors (the estrogen receptor and progesterone receptor) and the HER2 oncogene (a gene which can transform a normal cell into a tumour cell). But a more aggressive malignancy, “triple-negative breast cancer,” doesn’t express hormonal receptors or the HER2 oncogene. As a result, no targeted hormone therapy exists for triple-negative breast cancer, so patients are treated with extremely harsh chemotherapies that indiscriminately kill proliferating cells, whether cancerous or not. Which results in the chance to develop a secondary cancer from such an overload of toxicity in the body, coupled with a destroyed immune system.
These three types of cancer – hormone-sensitive, HER2, and triple-negative – were used as models for “Appraising the entourage effect.”
In all models of breast cancer studied, in vitro and in vivo, the whole plant extract (FECO) was significantly more effective at producing anticancer effects than single-molecule THC. These results were broadly consistent for the type of cancer and model. In addition, researchers tested the compounds in cell cultures (Petri dishes) and rodent models (mice).
In the case of hormone-sensitive breast cancer cells, FECO was 15-25% more potent than THC alone. In live-animal models, single-molecule THC exhibited no significant antitumor response, unlike the whole plant extract, which had a pronounced antitumor effect. Testing on lab animals is a necessary step towards establishing the efficacy of a specific clinical treatment.
When the cannabinoid preparations were added to tamoxifen, a standard chemotherapy drug, in a cell plate, the combined therapy was about 20-25% more effective than chemotherapy alone. But these results were not replicated in live-animal trials. Significantly, the cannabinoids also did not negatively impact the efficacy of the chemotherapy. This suggests that, at the very least, using cannabis as an add-on treatment to deal with common side effects of chemotherapy, like nausea and appetite loss, won’t impede chemotherapy’s ability to destroy cancer cells.
In hormone-sensitive breast cancer, it appears that THC produces effects via interaction with the CB2 cannabinoid receptor. CB2 receptor activation has received significant attention because of its potential to treat diseases while avoiding the “high” mediated by the CB1 cannabinoid receptor, which THC also activates. When THC binds to CB1, it causes the swimmy-headed feelings of intoxication associated with cannabis consumption.
FECO was significantly more potent than THC alone, for HER2-positive breast cancer cells. However, both single-molecule THC and FECO showed antitumor effects when the experiment was replicated in mice. Additionally, THC and the entire plant extract amplified the anticancer effects of lapatinib, the standard chemotherapy drug for HER2 breast cancer.
As with hormone-sensitive breast cancer, THC’s antitumoral effect in HER2-positive breast cancer experiments was mediated by the CB2 cannabinoid receptor. Published in the Proceedings of the National Academy of Science, a subsequent report by Cristina Sanchez and other Spanish scientists noted that HER2 and CB2 receptors are often found in the same place on cells.
CB2 conjoins with HER2 – forming what is called a dimer – and this dimerization is associated with poor treatment outcomes for breast cancer. The PNAS report shed new light on THC’s anticancer mechanism of action: When THC binds to the CB2 receptor, it breaks up the CB2-HER2 dimer, triggering a chain reaction of signals that culminate in tumour regression.
Triple-negative, the breast cancer subtype with the worst prognosis, does not generally respond well to chemotherapy. Again, FECO was found to be more effective than THC alone in decreasing the viability of cancer cells in vitro as well as in mouse model studies.
The results of the Spanish study, along with compelling data from other researchers, suggest a promising future for whole-plant cannabis oil extracts and multi-target cancer therapies. But the Western medical system and its typical drug development procedures are not conducive to the approval of complex botanical preparations as multi-target medicaments – in part because elucidating a precise mechanism of action when numerous compounds are involved is much more complicated than studying a single-molecule pharmaceutical that’s geared toward a single, primary outcome.
The fact that both the THC isolate and FECO were shown to be effective at reducing tumour viability is truly groundbreaking and should be an impetus for advancing the development of nontoxic, cannabinoid-based treatments for breast cancer.
Cannabinoid therapies are particularly promising for tumour-producing cancers given that “no overtly cannabis-resistant tumors have been described so far,” according to the Spanish researchers. “Considering how different cancer subtypes are, and the fact that the viability of non-transformed cells is not affected by cannabinoids at the concentrations they kill tumour cells, it is tempting to speculate that these compounds tackle essential, as yet unidentified, cellular functions that all cancer cells share, and that are absent in their non-cancerous counterparts.”
The Spanish breast cancer study underscores the importance of the entourage effect by demonstrating that FECO with numerous cannabinoid components, is more effective than pure THC. Although the pharmacology of cannabis drug preparation extracts is obviously more complex to study,” the researchers acknowledge, “this therapeutic approach has the potential to produce better therapeutic responses than pure cannabinoids.”
The Spanish scientists emphasize that FECO “did not, in any case, diminish the antitumor efficacy of any of the standard treatments.” That’s good news for cancer patients who use cannabis to manage the adverse side effects of chemo.
Cannabis is safe for not only treating the direct effects of chemo, such as pain and nausea and for appetite stimulation. But, it's also highly efficient in causing apoptosis (cancer cell death).
Obviously, it is much safer to use cannabis treatment as part of a holistic protocol, but if the patient does decide on conventional treatment, it's important to note that cannabis can help reduce the main effects of chemo and does not interfere with the medication, whilst helping protect the non-cancerous healthy cells.
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