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What should I know about cannabis and cancer treatments?

Don't panic.
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Suppose you have landed on this page after first reading the riveting tale of Goldilocks and her taste for cannabis. In that case, you are one of three types of people, because three is a theme that totally makes sense if you read the previous article. You may be an all-around inquisitive type, with a thirst for knowledge that only thepineapple can quench in just the right way, or you or a loved one have cancer—If you are among the latter, then man, that sucks. However, don't panic! While this is not the suitable format to delve into too much detail, let me provide you with a canvas you can use as a frame of reference when you engage your doctors. I know, a lot of you will primarily be looking for cannabis specific information here. Nevertheless, I would like to take the opportunity to give you some brief general cancer tips, because not only is the medical industry extremely opaque to the laymen, but with cancer in particular, decisions you make early on during your treatment can have massive long-term consequences on overall survival. Of course there are many types of cancers each with their own set of challenges and specific therapy options. But there are some big picture commonalities we’ll point out here that should help you ask the right questions when you meet with your oncologist. But if you are here only for the cannabis then I’ll say this, cannabis can be useful to mitigate some of the symptoms of cancer and the related therapy. But not all treatments are compatible with cannabis. So you must always discuss cannabis with your oncologist to ensure it does not interfere with your primary medications.

First diagnosis

When you first get the diagnosis, it can be pretty nerve-wracking and confusing, and it is easy to feel overwhelmed. But there is a structure to everything. The medical realities of how cancer is being treated are constantly changing. And hope isn't lost yet. So don't give up. I have seen patients with a terminal diagnosis and 3 months left find a clinical trial that helped them survive. Cancer research is moving very quickly and there have been some world-changing breakthroughs especially in the realm of targeted, T-cell based immunotherapies (CAR-T). Unfortunately, there is a lot of inertia before the scientific discoveries are translated into common clinical applications. What that means is that cancer is being treated in many clinics, but it isn’t necessarily treated at the state-of-the-art.

Find an oncologist who can help you navigate current clinical trials

Cancer science moves so very quickly and the state-of-the-art can mean the difference between surviving for years instead of a few months. Therefore the most important thing for you to understand is that not every oncologist is equal. Find yourself a treatment provider that can help you navigate http://www.clinicaltrials.gov. If your oncologist doesn’t know what that is, then you should probably go look for another one. 

Here are some questions you need to ask your doctor:

  1. Which cancer type was diagnosed?

  2. What "stage am I classified" as?

  3. What is the current FDA-approved method of treatment?

  4. Is the therapy "targeted" (immunotherapy), or is it "non-specific" (like IFN-gamma treatment)? 

  5. What clinical trials for your cancer is your doctor aware of?

  6. What are the "exclusion" / "inclusion" criteria for those clinical trials?

Also as a side-note, clinical trials usually cover the treatment costs. So also keep that in mind. 

That seems like a lot, and not everything makes sense to you right now. Still, they are all important questions that I will help you understand by walking you through a personal experience with a close family member who was diagnosed with skin cancer (malignant melanoma.) By the time my relative was diagnosed, his disease progression was classified as "stage IV." The staging is important because it defines at what stage of the disease progression you were diagnosed. The categories are stage 0 - stage 4(IV). The lower the number, the earlier along the path you are. In the case of my relative, he was diagnosed at stage IV. That is the last stage. At this point, the cancer has already spread (metastasized) to other organs. For him, it was several lymph nodes, the liver, his small intestines, lung, and brain. He was given several months to live at best, and the oncologist recommended "IFN-gamma" as a chemotherapy treatment. That was almost a decade ago, and my relative is still alive with very few disruptive symptoms. 

What to pay attention to 

Luckily for us, I knew three things that helped us out. The rule of three striking yet again. 

  1. Doctors tend to recommend FDA-approved methods. 

  2. Targeted cancer-therapy has a better chance of stopping the disease than non-specific chemotherapy (provided you can hit the target)

  3. You have to be aware that clinical trials have exclusion criteria. 

Ok, so what does that mean? First, you can't really fault doctors for sticking to FDA-approved methods. Aside from trying to save you, they also need to make sure they don’t harm you in the process. FDA-approved methods minimize the risk of causing harm. The problem is for many cancer types the current FDA approved therapies sometimes only have minor, yet statistically significant impact. That means, let's bring up the IFN-gamma example again. Statistically, patients that take the therapy will live maybe 3 months longer. But that comes at the cost of suffering the side-effects of the drug for years. Is it worth being absolutely miserable for 3-5 years in order to live 3 months longer? Personally, I would probably choose quality-of-life over a minor life extension—But this will be something you’ll have to answer for yourself. So, when you discuss the FDA approved treatment your oncologist recommends, always also ask the question of what the average scenario for the therapy is and what the impact on quality-of-life will be.

Cancer research has slowly been moving toward intelligent, personalized, targeted therapy for years. Most of which is still in various stages of clinical trials. In my relative's case, I was aware of one of those trials starting recruitment a couple of months down the line. It so happens that previous treatment with the current FDA-approved "IFN-gamma" would have been an "exclusion" criteria for that trial. So had my relative chosen to follow the oncologist's recommended path, he would have missed out on the trial that ultimately prolonged his life so dramatically. 

In a practical sense, what I suggest is that you ask your doctor about clinical trials. If your doctor isn't aware of any, then swap doctors. Because especially when it comes to cancer treatment you want your doctors to be aware of the current state-of-the-art.  In the meantime, you can find all clinical trials listed in this international database: http://www.clinicaltrials.gov

The trials are organized by region along with information about which stage of cancer the trial is for, exclusion criteria, and contact information. Now, I am not saying participating in a trial is always the correct choice. That depends on many factors. But what I am saying is that you need to make sure your oncologist helps you navigate that decision. Finally, another thing to know is that trials will often cover your medical cost while participating.

Cannabis?! I am here for cannabis!

So where does cannabis fit into all of this?—In the context of cancer and chemotherapy, cannabis can potentially be useful to mitigate some of the unpleasant symptoms that you might be experiencing as a result of the cancer or the therapy for it. Like for example chemotherapy induced nausea and vomiting. It is very disruptive and unpleasant for the patient and mitigating those effects is quite valuable for both the patient’s physical and mental well-being. 

As medications go cannabis can be dosed to be relatively mild and since the cannabinoid receptors are so ubiquitous in the body, it can be applied for a variety of problems. The NIH National Cancer Institute identified the following use cases for cannabis in the context of cancer: 

  • Stimulate appetite
  • Relieve nausea/vomiting
  • Treat anxiety
  • Improve sleep quality
  • Pain relief

Alleviating some of those symptoms can significantly improve a patient's quality-of-life. Cannabis has been a potent recommendation for this. Especially, when it comes to pain relief and nausea mitigation. But never use cannabis without consulting your oncologist. The cannabis plant is a polypharmacy of biologically active molecules.

Cannabis can help with quality-of-life and mitigate some cancer symptoms. However, it can interfere with treatment !

It is important to note that this entourage of compounds can interfere with other medications that are essential to your treatment and/or could be an exclusion criterion for a clinical trial you may need. So, while cannabis is a tool you could use to improve quality-of-life and mitigate some of the negative symptoms, if you do so instead of treating the underlying condition then the outcome won’t be favorable. The primary treatment should always take precedence.

Marijuana is not compatible with every cancer therapy

Over the course of this article, I have pointed out several times that you must always inform your oncologist about your weed usage. That is because there is a very real risk that the active compounds in the plant interfere in some way with the therapy. Unfortunately, that risk isn’t even very remote. The reason is that cannabinoid receptors are everywhere in the body. This is both a gift and a curse. It is a gift, because as we discussed before, it means marijuana may be used to mitigate various kinds of unpleasant side-effects, but it is also a curse, because the active compounds in the plant interact with the cannabinoid receptors found on the cells of the immune system. This should give every oncologist pause, because many of today’s most successful anti-cancer strategies involve taking advantage of the inherent base function of the immune system to kill cells that don’t behave as they should. Targeted immunotherapy is by far the most promising way of tracking down and eliminating metastasis after they have spread through the body. Unfortunately, there have been quite a number of scientific studies that demonstrate how cannabinoids like delta-9 THC alter and even diminish the effectiveness of some very critical immune cells like T-cells. Incidentally, this is the reason why you would want to take a tolerance break in the days leading up to and immediately after vaccination, like for example against COVID-19—But In the context of anti-cancer immunotherapy this is even more important because T-cell immunity is critical for the success of the treatment.  

To give you a specific example of this. A few weeks ago we covered a rather important brand new scientific study in our “journal club #37”.

Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2.”, Xiong et al. Signal Transduct Target Ther. 2022 Apr 6;7(1):99. 

T-cell immunity is critical for the success of many cancer treatments

The high-impact paper by Xiong et al. very convincingly demonstrates that delta-9 THC, the main psychoactive component of marijuana impedes the function of immune checkpoint inhibitors. Ok, let me translate that for you. Those “inhibitors” are a key component of anti-cancer immunotherapy. Specifically, they are routinely used to treat advanced stage metastatic melanoma, i.e. skin cancer. Currently, this is one of the best and most widely used forms of therapy against skin cancer. The idea behind the treatment is to block a mechanism the cancer cells use to evade the immune system. As it can cause unwanted side-effects like nausea, cannabis is often used to manage those adverse effects, but, in this context the immunosuppressive effects of delta-9 THC impairs the function of the anti-tumor specific T-cells that are the core component of the therapy. In other words, if you use marijuana to mitigate the symptoms it comes at the cost of poor overall survival. 

So in the case of metastatic skin cancer consuming cannabis is definitely not a good idea. Basically, if your oncologist mentions “T-cells” in any way it is probably wise to bring up cannabis and discuss possible unfavorable interference with your planned therapy.

Finally, some studies have suggested direct beneficial effects of cannabinoids on some cancer cells. For example, research indicates that cannabinoids can inhibit specific liver and breast cancer cells. And there is some evidence of it synergizing with some forms of chemotherapy. But while there is some promise in that research, it is certainly not far enough along to be immediately applicable to the clinic, nor is it likely that the whole marijuana plant will ever be an outright treatment for cancer. It is just biochemically not well enough defined for it to be used that way. Of course, that doesn’t stop mainstream media from strapping the cart before the horse and writing headlines about how cannabis can cure cancer.—That being said, it does look like the endocannabinoid system is involved in some cancer pathogenesis, i.e. the disease progression. So cannabinoids like THC or CBD could potentially be useful tools to help researchers unravel the role of the endocannabinoid system in those diseases and in turn this may one day lead to more specific, targeted treatments against cancer. Of course, while that is of academic interest it is of little use to you if you have just been diagnosed with cancer. Instead you’ll be looking for what to do about it right now and in the immediate future.

References:

  1. Meng, Howard et al. “Cannabis and cannabinoids in cancer pain management.” Current opinion in supportive and palliative care vol. 14,2 (2020): 87-93. doi:10.1097/SPC.0000000000000493 https://pubmed.ncbi.nlm.nih.gov/32332209/
  2. Chung, Matthew et al. “Update on cannabis and cannabinoids for cancer pain.” 
    Current opinion in anaesthesiology vol. 33,6 (2020): 825-831. doi:10.1097/ACO.0000000000000934 https://pubmed.ncbi.nlm.nih.gov/33110020/
  3. Shin, Sarah et al. “An Integrated Review of Cannabis and Cannabinoids in Adult Oncologic Pain Management.” Pain management nursing : official journal of the American Society of Pain Management Nurses vol. 20,3 (2019): 185-191. doi:10.1016/j.pmn.2018.09.006 https://pubmed.ncbi.nlm.nih.gov/30527857/
  4. Hong, Mihe et al. “Engineering CAR-T Cells for Next-Generation Cancer Therapy.” 
    Cancer cell vol. 38,4 (2020): 473-488. doi:10.1016/j.ccell.2020.07.005 https://pubmed.ncbi.nlm.nih.gov/32735779/
  5. Sanlorenzo, Martina et al. “Role of interferon in melanoma: old hopes and new perspectives.” 
    Expert opinion on biological therapy vol. 17,4 (2017): 475-483. doi:10.1080/14712598.2017.1289169 https://pubmed.ncbi.nlm.nih.gov/28274138/
  6. Whiting, Penny F et al. “Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.” JAMA vol. 313,24 (2015): 2456-73. doi:10.1001/jama.2015.6358 https://pubmed.ncbi.nlm.nih.gov/26103030/
  7. Grimison, P et al. “Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 31,11 (2020): 1553-1560. doi:10.1016/j.annonc.2020.07.020 https://pubmed.ncbi.nlm.nih.gov/32801017/
  8. Abrams, D I, and M Guzman. “Cannabis in cancer care.” Clinical pharmacology and therapeutics
    vol. 97,6 (2015): 575-86. doi:10.1002/cpt.108 https://pubmed.ncbi.nlm.nih.gov/25777363/
  9. Maggirwar, Sanjay B, and Jag H Khalsa. “The Link between Cannabis Use, Immune System, and Viral Infections.” Viruses vol. 13,6 1099. 9 Jun. 2021, doi:10.3390/v13061099 https://pubmed.ncbi.nlm.nih.gov/34207524/
  10. Xiong, Xinxin et al. “Cannabis suppresses antitumor immunity by inhibiting JAK/STAT signaling in T cells through CNR2.” Signal transduction and targeted therapy vol. 7,1 99. 6 Apr. 2022, doi:10.1038/s41392-022-00918-y https://pubmed.ncbi.nlm.nih.gov/35383142/