Cannabis with breast cancer treatment, more harm than good?

Cancer can be a very scary word, and if you or a loved one has had a recent diagnosis then you are tossed into a whirlwind of information. Eat this but not that, exercise but only do it this way, eat vitamins but only this kind and the list goes on and on. Cannabis is among those common natural product recommendations, from friends, online forums or even a physician, but is it worth the hype? Or does it cause more harm than good? Keep reading to learn more about potential interactions of cannabis and breast cancers treatments.


Chemotherapy – Cancer Treatment

Chemotherapy (chemo), a common cancer treatment, can be effective but not without its mild to life-threatening effects. Some of these include loss of appetite, nausea, vomiting, hair loss, fatigue, mouth sores, weight changes, infertility, and various toxicities (Tao et al. 2015). Some types of chemo stop all rapidly dividing cells, including healthy ones, this leads to the aforementioned list of side effects. While others, such as Tamoxifen (an orally prescribed form of chemo) work by blocking estrogen signaling for cell division in breast cancers that are Estrogen Receptor Positive (ER+), therefore it is not effective on cancers that are Estrogen Receptor Negative (ER-). This is more targeted and does not cause the same side effects as the first option. 

Cannabis effects on symptoms relating to chemotherapy

Cannabis has been employed by those undergoing chemo to help relieve associated symptoms (Parker et al 2011; Wasik et al 2011). However, there have been limited studies focused on herb-drug, drug-drug, or disease-drug interactions with cannabis and chemotherapy. This is partly to do with strict legal and regulatory laws that limit accessibility for researchers. Therefore, data for cannabis use mostly stems from non-scientific observations though sites such as Leafly (online self-declaring symptoms/reactions), and only 25% of medicinal cannabis users were guided by a professional.  

What if cannabis itself could stop cancer from spreading?

Let’s take cannabis use a step further, what if it can actually stop cancer from spreading rather than just treat symptoms of chemo? A recent study by Schoeman et al. aims to better understand the potential anti-proliferative (prevents spreading) effects of cannabis in breast cancer. 

There are 3 categories used to describe strains of Cannabis, but this classification system fails to acknowledge potential roles of more than 600 other compounds present in cannabis (Russo 2011). The potential interactions are known as “entourage effects”. Schoeman and their team tested “intra-entourage effects” (between various phytocannabinoids, cannabinoids found in cannabis) and “inter-entourage effects” (between phytocannabinoids and phytochemicals, chemicals found in cannabis) in two cell lines representing two common types of cancer. One cell line has estrogen receptors (ER+), and the other does not have estrogen receptors (ER-).

Categories of cannabis. Graphics are my own.

Authors used pure cannabinoid formulations either being mostly THC (Recreation Cannabinoid Only) or low in THC (Medicinal Cannabinoid Only) to model “intra-entourage effects”. Since cannabis is rarely used in isolated cannabinoid forms and more commonly smoked, consumed as edibles or extracts from cannabis, understanding “inter-entourage effects” are imperative to better classify the safety and efficacy of cannabis products. Therefore, cannabis extracts that also contain other compounds found in cannabis (ie, terpenes) were used. Similarly, these samples are either high in THC (Recreational Extract) or low in THC (Medicinal Extract). Detailed information about ratios and phytochemicals can be found in the original article here.

Definition of intra and inter- entourage effects. Graphics are my own.

Results:

With these two cell lines the authors were able to test the four different formulations to see potential “intra-“ and “inter-“ entourage effects. Dose-response curves were created to compare the eight combinations. 

“Intra-entourage effects”

Recreational Cannabinoid Only was more efficacious than Medicinal Cannabinoid Only in ER- at the IC50 mark (half the cells are dead) but Medicinal Cannabinoid Only was more efficacious than Recreational Cannabinoid Only at IC75 and IC90 (at which 75% and 90% cells are dead, respectively). For ER+, Recreational Cannabinoid Only was more efficacious then Medicinal Cannabinoid Only at all concentrations tested. Looking at the two cell lines, Recreational Cannabinoid Only was more efficacious in ER+ and Medicinal Cannabinoid Only in ER-. The differences observed between recreational and medicinal are likely due to the expression (or lack of expression) of the ER. Since Recreational Cannabinoid Only had a higher THC content and knowing that THC can also act on cannabinoid receptors 1 and 2, THC could be exhibiting dual anti-proliferative effects at these receptors plus the ER. On the other hand, high CBD concentration formulations may act independent of the ER and show more efficacy in the ER- cell line since there is no ER expression. Overall, this data suggests there may be an “intra-entourage effect” present and more research should be conducted. 

“Inter-entourage effects”

In the medicinal formulations for both the Extract and Cannabinoid Only, the anti-proliferative effects remained relatively unchanged. Whereas the recreational formulation with phytochemicals (Extract) decreased the efficacy of the Recreational Cannabinoid Only in both cell lines. Since the differences observed for presence of phytochemicals were not significant, the effect observed is likely due to the different ratios of THC:CBD and not due to the phytochemical present.  

Conclusions for intra-entourage effects. Graphics are my own.

So does Cannabis interfere with the efficacy of chemotherapy?

The short answer is yes it interferes with the efficacy of chemo drugs. In the study, authors used Tamoxifen (Tam) to test cannabis effects in the presence of a chemo drug. Tam was tested alone and in the presence of all 4 formulations. 

Recreational and medicinal formulations each with Tam, were less toxic and in cancer drug terms, less effective since the goal is to kill the cancer cells.  Tam alone had the highest EC50 (which means the least amount of drug required to kill half the cells). It was more obvious in the recreational formulations which indicates that THC could have a greater impact on the anti-proliferative effects of Tam. Another possibility is that Tam and CBD, both toxic on their own, could be experiencing some synergistic effects making it slightly more toxic than THC and Tam together. 

So what did we learn?

There may be some “intra-entourage effects” at play here and that cannabis used alongside chemo treatment may actually hinder the efficacy of chemo. Furthermore, to maximize safety and efficacy, there should be more emphasis on individual cannabinoid formulations based on the type of cancer, rather then a “one-size fits all” treatment. This is a great start to understanding these interactions and more research should be done with other chemo reagents, but caution should definitely be exercised when making the decision to consume cannabis products while undergoing chemotherapy treatments, especially since this study was done in vitro (in cells) and not in humans. Another point to consider, in order to best understand the interactions with Tam, studies should test Tam in the presence of just CBD and just THC. This is because CBD has shown positive synergistic effects when used with other chemo drugs but research suggests that this is hindered when in the presence of even a small amount of THC. Lastly, only one chemo drug was tested and thus, more studies on varies chemo drugs should be considered.

*Natural Health Products do not always mean safe, so make sure to consult with your physician before trying new products, such as cannabis, in conjunction with other medication. 

PS: This is an assignment for school, if you have any questions please feel free to reach out or comment below.


~Tori Scherle~
BSc Biology
MSc Biology Candidate
Quality Assurance Quality Control Cannabis Trainee
University of Ottawa, Ontario

References and resources from above:
– Schoeman, R., de la Harpe, A., Beukes, N. & Frost, C. L. Cannabis with breast cancer treatment: propitious or pernicious? 3 Biotech 12, 1–12 (2022). Link here.
– Tao JJ, Visvanathan K, Wolff AC (2015) Long term side effects of adju- vant chemotherapy in patients with early breast cancer. The Breast 24:S149–S153. https:// doi. org/ 10. 1016/j. breast. 2015. 07. 035. Link here.
– Parker LA, Rock EM, Limebeer CL (2011) Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol 163:1411–1422. https:// doi. org/ 10. 1111/j. 1476- 5381. 2010. 01176.x. Link here.
– Wasik A, Almestrand S, Wang X, Hultenby K, Dackland Å-L, Anders- son P, Kimby E, Christensson B, Sander B (2011) WIN55, 212–2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells. Cell Death Dis 2:e225–e225. https:// doi. org/ 10. 1038/ cddis. 2011. 106. Link here.
– Russo EB (2019) The case for the entourage effect and conventional breeding of clinical cannabis: no “strain”, no gain. Front Plant Sci 9:1969. https:// doi. org/ 10. 3389/ fpls. 2018. 01969. Link here.
– Leafly database for cannabis reactions, side effects, strain information and more. Link here.
– More information on Tamoxifen. Link here.
– More information on phytocannabinoids including a list of articles. Link here.
– More information on phytochemicals including a list of articles. Link here.

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I'm 22 years old and starting my Masters in Biology at the University of Ottawa in September. I just recently graduated with my Honours BSc - Biology. I love photography, baking, plants & adventures!

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