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Should you take a cannabis tolerance break for the COVID vaccine?

Interactions between cannabis and vaccines
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It is 2021 and COVID-19 is still on everyone’s mind, and since there is a rapidly expanding number of SARS-COV-2 variants, this likely won’t change any time soon. Luckily, we have access to a selection of vaccines that add a much needed layer of protection against COVID-19. The good news is, by now millions of people have already been successfully vaccinated, confirming and bolstering the DATA from the clinical trials and statistics tell us that the COVID-19 vaccines are both effective and quite safe.

The short answer: YES ! take a break in the days before and after vaccination

The bad news is, consuming cannabis alters the immune system response to vaccines. So if you are actively consuming cannabis during the vaccination period you may be robbing yourself of that much needed vaccine protection. Therefore, going on a tolerance break leading up to and during a vaccination seems like a smart idea.

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The immune system in a nutshell

To understand why we recommend a tolerance break leading up to and in the days after a vaccination you will need to understand some fundamental principles of the hugely complex immune system. So I will break it down into the essentials :

The first thing you need to know is that the majority of pathogens fail to get past our #1 layer of defense, our skin. For example, the SARS-COV-2 virus won’t infect you if you have it on your hands. Your skin would have to have an open wound for an infection to get past its barrier. However, if you have the virus on your hands and then touch your face you risk exposing the mucosal membranes of the eyes, mouth and airways to the virus, which will increase your risk of infection dramatically. Should a pathogen cross the barrier of the skin it will face the rest of the immune system. The immune system is one the most complex systems of the human body. It consists of a highly interconnected web of cells that are designed to identify, categorize, quantify, clear and remember the threats against your body’s ecosystem.

Beyond the skin, the second line of defense consists of non-specific responses against the invaders. Your immune system does not yet know who it is dealing with, but it is equipped with a number of pattern-recognition mechanisms that can non-specifically neutralize pathogens. From an evolutionary point of view, this “innate'' non-specific immune response is considered to be the oldest part of the immune system. On a very high level, it consists of a number of cells, mostly phagocytic cells, i.e. amoeba-like white blood cells (leukocytes) that chase after bacteria and smaller foreign objects, and “eat” them, as well as the “complement system” , a protein based “self-assembling” hole making mechanism which attacks bacterial cell walls, literally punching holes into them, while also making the pathogens extra “tasty” for the phagocytic cells. You can see a video of a phagocytic cell chasing a bacterial cell below. Incidentally, this is why inflammation hurts. Those phagocytic cells squeeze inbetween the endothelial cells forming your blood vessel in order to get to injured or infected tissue. You'll perceive that as swelling and pain.

The “innate'' non-specific immune response acts quickly and can distinguish between the overall categories of pathogens it encounters. In other words, it can tell apart a parasite from a virus, bacteria or fungus, but it cannot tell which specific bacteria or virus it is. However, what those first-line phagocytic cells can do is “recruit” other more specialized immune cells that are able to mount an “adaptive / specific '' immune response against a specific pathogen. To that end the cells of the immune system are in constant communication with each other.

cells of the immune system are in constant communication with each other.

They communicate either via direct cell-to-cell contact, i.e by “touching” each other’s receptors at close range or via the release of longer range signaling molecules (cytokines) into the tissues and blood stream. You can think of those cytokines as “pheromones'' for immune cells that help regulate the immune response. There are many different kinds of cytokines that convey a lot of information depending on their concentration and specific mix that is released into the tissue around the site of infection and into the bloodstream. The concentration of the cytokines is the highest around the site of infection. This allows cells to move along a concentration gradient and home in on the site of infection from very long distances. Furthermore, the exact “mix” or cocktail of cytokines provides the immune system with information about what type of infection it is dealing with.

Imagine all of your blood and tissue fluids as one big glass of water. When the immune system cells take a sip and it tastes like water, then you are healthy. If it contains a certain mix of cytokines, it is suddenly sweet. Sweet could mean there is a viral infection in your body. A different mix of cytokines could make it taste spicy and that might mean there is a bacterial infection. The overall milieu, i.e. mix of cytokines in the blood and tissue “primes” the cells of the immune system to mount either an antiviral, anti-bacterial, anti-fungal or anti-parasitic defense. The concentration gradient of the cytokines tells the immune system where in the body the infection is. Meanwhile, the cytokine signal is combined with direct cell-to-cell interaction between cells presenting actual fragments of the pathogen to cells of the specific/adaptive immune system. It is this combination that informs what kind of immune response the immune system decides to mount.

This is important, because the immune system needs to switch between different modes of action that can be mutually exclusive. For example, if a virus is floating around in the tissue and the space between the cells, but hasn’t yet entered the individual cells, we will need a “humoral” response that aims to produce antibodies which bind to the virus, block its action and clump it together into aggregates that phagocytic cells can then clear away. - But, if the virus has already entered its target cell and is taking over its host’s biosynthesis machinery, then we need a cell-mediated response where cytotoxic cells identify and then kill the infected cells. But if there is a parasite present we need an entirely different response.

However, since the immune system is sharing “one big glass of water” it has to choose one or the other. If the glass of water was sweet, sour and spicy at the same time, then the immune system would not know what to fight. To prevent this confusion, the cytokines are tightly regulated. So, if enough cells are releasing “sweet” cytokines and direct cell-cell interaction says “virus”, then a suppressive signal is sent to the cells shouting at “spicy” and “sour” to shut up and focus on “sweet” for now. Once the message is unified to “sweet” the adaptive immune system can do its thing. Cloning its specific effector cells, produce antibodies and cytotoxic cells, culminating in the production of a set of “memory” cells that lie in wait for the next re-infection with the defeated pathogen, so that next time we can skip a large portion of lead process and skip straight to the killing part. So then how do the COVID vaccines work ?

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COVID vaccines and the “sweet” taste of a TH1 immune response.

Now that you understand the bare fundamentals of how the immune system functions let’s look at the COVID vaccine cliff notes. The basic principle of vaccine induced immunity is simple. You present the phagocytic cells of the “non-specific” innate immune system with a “dummy” fragment of the SARS-COV-2 virus. This is the “spike” protein you will have heard about in the news. The phagocytic cells recognize the “spike” fragment as a foreign virus and then send out cytokines into the big shared metaphorical “sweet glass of water” to recruit the adaptive immune cells to come and have a look at that “spike” protein. The adaptive immune system acknowledges the presence of a virus, starts producing effector and memory cells that clear the infection away and then remembers the whole ordeal for next time so it can skip straight to the killing part. The COVID vaccines differ in the method of delivering the “dummy” spike protein fragment to the phagocytic cells. BioNtech/Pfizer and Moderna use a modern nanoparticle that is essential a tiny fat bubble which contains synthetic RNA that holds the code for the spike fragment, while the other manufacturers like AstraZeneca and Johnson & Johnson are using another living, yet harmless lab-grown adenovirus that acts as a vector for delivering a synthetic DNA molecule into cells at the injection site. The delivery vectors are different but the outcome is the same.

Let’s use the original BioNtech vaccine as an example: The phagocytic cells come across the fat nanoparticles at the injection site and eat them. The particle releases the RNA molecule into the cell which is then read alongside all the other RNA molecules by the host cell’s biosynthesis machinery. When the RNA is read it produces the spike protein. RNA like this is not very stable and can only be read for a limited amount of time. So, after a short while the only thing that remains from the BioNtech vaccine is the “spike protein fragment”, as both the lipid droplet and the RNA will have been consumed. Subsequently, the spike protein elicits an immune mode switch which culminates in an immune response and memory formation. After this has happened there is no trace of the vaccine anymore. Only the immune memory remains. The original creators of the BioNtech vaccine published a paper last September describing and characterizing what type of “immune mode” the vaccine was stimulating. In conclusion they verified that their vaccine skewed the immune response of their patients towards a “cell-mediated adaptive TH1 response that is characterized by the expression of two major TH1 cytokines : IFN-gamma and Interleukin-12”. To rephrase this with the glass of water metaphor, IFN-gamma and Interleukin-12 are two cytokines that turn the glass of water “sweet” which is consistent with a specific cell-mediated antiviral response.

Cannabis affects the “Immune Mode Switch”

The cannabis plant is filled with phytocannabinoids. The two most famous ones being delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). These phytocannabinoids interact with the body’s natural endocannabinoid system via a number of cell membrane receptors. The two most well studied ones are cannabinoid receptor 1 (CR1) and cannabinoid receptor 2 (CR2). CR1 is mainly found on the cells of the peripheral and central nervous system, while CR2 can be found on but not limited to a variety of immune cells. Overall, the endocannabinoid system is extensively expressed through-out all major organs of the human body and plays a role in maintaining and facilitating “homeostasis”, which can be described as the process of returning cells back to their default resting state. If you would like to learn more about homeostasis and the endocannabinoid system, then check out our article: "Goldilocks, cannabis and the endocannabinoid system (ECS)".

So what happens to the immune system when you consume cannabis?—Well, since cannabinoid receptors were found on immune cells, there has been quite a bit of research evaluating how the “immune mode switch” is affected by phytocannabinoids. In particular delta-9 THC. The conclusion that is echoed from several directions of the research community is that delta-9 THC suppresses the “adaptive cell-mediated TH1 immune mode”, at different points throughout the chain of the immune response. It affects the initial phagocytic cells that sound the alarm and all of the important cells along the cascade of the adaptive immune response. In other words, it prevents the glass of water from tasting “sweet” so the antiviral immune response is suppressed.

A church constructed from spent BioNtech/Pfizer vials (Paderborn, Germany)

So ultimately how does cannabis affect the COVID vaccine?

To summarize this whole ordeal. If you take a COVID vaccine the idea is that you trick the immune system into activating a specific adaptive immune response mode (TH1). The immune response culminates in the formation of memory cells that lie in wait until you actually encounter the REAL coronavirus. When that happens the memory cells can skip right to the chase and effect the virus out of existence.

Cannabis suppresses the immune response required for vaccination to work

If you consume cannabis leading up to or during the week following vaccination, you are likely actively suppressing the TH1-mode-immune response that is required for the vaccine to function and do its job. Therefore your immune system likely won’t produce memory cells properly, thus possibly rendering the vaccine useless. So in conclusion, it would be wise to take a break from cannabis in the week before the vaccination and in the week after the vaccination in order to allow enough time for the vaccine to function. As an added bonus you will reduce your cannabinoid tolerance, so when you smoke cannabis again after your 2 weeks of abstinence the experience will be that much more potent.

If you made it this far and are still confused about things. Then maybe have a look at this Family Guy episode. And just consider, that all the cells fighting the infection are on a smoke break.

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https://www.youtube.com/watch?v=zDQuwkJIBaY

References:

  1. Punt, J., Stranford, S. A., Jones, P. P., & Owen, J. A. (2019). Kuby immunology. https://www.worldcat.org/title/kuby-immunology/oclc/1002672752
  2. Sahin, U., Muik, A., Derhovanessian, E. et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020). https://doi.org/10.1038/s41586-020-2814-7
  3. Miranda, K., Mehrpouya-Bahrami, P., Nagarkatti, P. S., & Nagarkatti, M. (2019). Cannabinoid Receptor 1 Blockade Attenuates Obesity and Adipose Tissue Type 1 Inflammation Through miR-30e-5p Regulation of Delta-Like-4 in Macrophages and Consequently Downregulation of Th1 Cells. Frontiers in immunology, 10, 1049. https://doi.org/10.3389/fimmu.2019.01049
  4. Klein, T. W., Newton, C., Larsen, K., Chou, J., Perkins, I., Lu, L., Nong, L., & Friedman, H. (2004). Cannabinoid receptors and T helper cells. Journal of neuroimmunology, 147(1-2), 91–94. https://doi.org/10.1016/j.jneuroim.2003.10.019
  5. Sido, J. M., Jackson, A. R., Nagarkatti, P. S., & Nagarkatti, M. (2016). Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation. Journal of molecular medicine (Berlin, Germany), 94(9), 1039–1051. https://doi.org/10.1007/s00109-016-1404-5