ThePineapple - A brief look at COVID and cannabis.

[Part 1/3] What you should know about cannabis and COVID-19

Surprise! Social media have been taking things out of context, again.

The COVID-19 pandemic has now been plaguing us since 2019, pun intended. Everyone is fed up with it. Lots of people have died, many in preventable fashion. But our daily lives have been impacted in more than just the public health and death kind of way. The economy seems to be at a tipping point, extremism is on the rise and the world is on the verge of a third world war. All of this is exacerbated by an epidemic of misinformation that is making everything so much worse. In particular, there have been a number of scientific publications on COVID and cannabinoids that splashed onto social media and were taken wildly out of context. To remedy this and to dispel some of this misinformation we are going to provide you folks with an evidence-based framework of basic knowledge and hopefully empower you to make good decisions about cannabis consumption during this pandemic.

by Zach Weinersmith (smbc-comics.com)

Bored in a house and in a house bored

There is so much fear, confusion and distrust of the medical industry, when now is exactly the time to listen to the experts that have dedicated their life’s work to studying and advancing our understanding of the immune system, infectious diseases and medicine. Everyone wants to heal, everyone wants to be safe and everyone just wants relief. Most of us retreated into our comfort zones, I mean quarantine zones. And statistics tell us that cannabis consumption saw a significant rise during the pandemic. Understandably so, since if you are bored in a house, and in house bored, then you may as well let your mind escape. Sensationalist headlines of various miracle cures keep sweeping the world over and over. And recently headlines like “Cannabis can prevent COVID-19!” are among them. But are the headlines in the media true? What does the science say? What should you know about cannabis and COVID-19? Well, as with many things there is a kernel of truth surrounded by a whole bunch of exaggerated hyperbole. Some of the headlines are true, some of them are not and some of them are misleading by omission. Unfortunately, while basically all of the relevant information is publicly accessible. For laymen, the clinical and biomedical research industries are extremely opaque and unintuitive. So unless you are already a part of the field or have acquired a significant amount of education it is impossible to distinguish what is or isn’t good and valid information. So, in this article, I will try and cut through the sensationalism for you to put things into context and hopefully allow you to better understand the state of knowledge and the pros and cons of cannabis during the COVID-19 pandemic.

The short answer is: No, consuming cannabis is not a universal cure for COVID-19

Cannabinoids can interfere with important drugs used to treat COVID-19 complications and counteract vaccine efficiency. However, there is some interesting new cannabinoid research that suggests some cannabinoids could be useful during the early stages of a COVID-19 infection. Which isn’t super applicable right now, but is an interesting stepping stone towards potentially finding cannabinoid based COVID-19 treatment options in the future.

Can cannabinoids prevent COVID infections ?

Of late, there has been a little bit of a media frenzy surrounding two recent scientific papers that both provide us with data suggesting cannabinoids could be used to block the coronavirus (SARS-CoV-2) from binding its target cells and trigger an innate immune response. In other words, potentially mitigating COVID-19 infections in the early stages. This has naturally led to a lot of excitement but also a lot of wrong conclusions, because the conversation often fails to provide the right context within the overall big picture of COVID. In order to provide you with this context I will need to give you a bit of prerequisite knowledge on how the coronavirus (SARS-CoV-2) binds to the cells of the human body and why this is a problem, before we circle back and I’ll go over the key findings of those two publications with you. But before we do that I am going to give you the cliff-notes up front. If you wish to understand the how and why, then continue on to part 2 & 3 of this series. Part 2 will give you some important general information on COVID-19 complications and vaccinations before we move on to discuss the new cannabinoid research findings in part 3.

Part 1: What you should know about Cannabis and COVID-19 <--- you are here

Part 2: The COVID side of this story

Part 3: Blocking COVID Infections With Cannabinoids ?

The “cliff-notes”

  1. The coronavirus (SARS-CoV-2) binds to human cells via the ACE2 receptor
  2. The ACE-2 receptor sits on a lot of important cells including blood vessels.
  3. The two most deadly COVID complications are blood clots and cytokine storm
  4. Blood thinners such as “baby-aspirin” can act preventative and lower the risk of blood clots
  5. Cannabis interacts with blood-thinners which under certain circumstances can be problematic
  6. Cannabis, especially the psychoactive delta-9 tetrahydrocannabinol (THC) interferes with vaccination.
  7. Cannabidiol (CBD) can lower cytokine storm in endothelial cells. Conversely, THC can make it worse in white blood cells (Macrophage Activation Syndrome).
  8. The cannabinoid precursors CBDA, THCA-A, CBGA but not CBD, THC and CBG can block virus entry into cultured cells in vitro (no animal or human data)
  9. CBD and its metabolite 7-OH-CBD inhibit SARS-CoV-2 replication and promote the host innate immune response during the early stages of infection. THC reverses this effect (animal and human evidence) - This new data suggests that pure CBD preparations which are already approved for treatment against epileptic seizures might turn out to be a useful prophylactic treatment for COVID-19 as well.
  10. 8 & 9 only applies to those specific cannabinoids and not whole cannabis flower or extracts.

RosnerLab at the University of Chicago
THC can interfere with several medications used for treating severe COVID complications

So, in other words. THC seems to be bad at multiple stages. It interferes with common treatments for potentially deadly COVID complications and also counteracts vaccine protection. Meanwhile, there is some early stage cell culture data that suggests some cannabinoid precursors like CBDA, THCA and CBGA can lower the ability of the virus to enter the cell. But we don’t have animal or human data for that. But keep in mind that heating those cannabinoid acids will decarboxylate them and thus remove the protective effects. Lastly, in a recent study it was demonstrated that CBD can slow down viral replication during the early stages of infection and promote beneficial innate immune responses. However, the authors are quick to point out that this applies only to CBD and its metabolite 7-OH-CBD and not other cannabinoids. Especially not THC which when present counteracts the effect of CBD. 

The scientists behind the study have this to say: 

“We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time”

“The purity of CBD and the chemical composition of the materials labeled as CBD are also important, especially in light of our findings suggesting that other cannabinoids such as THC might act to counter CBD antiviral efficacy. This essentially eliminates the feasibility of marijuana serving as an effective source of antiviral CBD”

continue to part 2 —>

References:

  1. Damkier, Per et al. “Interaction between warfarin and cannabis.” Basic & clinical pharmacology & toxicology vol. 124,1 (2019): 28-31. doi:10.1111/bcpt.13152 https://pubmed.ncbi.nlm.nih.gov/30326170/
  2. MGH News and Public Affairs "COVID-19 and Blood Clots". Harvard Medical School campus resource. Sep. 9 2020 https://hms.harvard.edu/news/covid-19-blood-clots
  3. Daher, Jalil. “Endothelial dysfunction and COVID-19 (Review).”Biomedical reports
    vol. 15,6 (2021): 102. doi:10.3892/br.2021.1478 https://pubmed.ncbi.nlm.nih.gov/34667599/
  4. Hojyo, Shintaro et al. “How COVID-19 induces cytokine storm with high mortality.” 
    Inflammation and regeneration vol. 40 37. 1 Oct. 2020, doi:10.1186/s41232-020-00146-3 https://pubmed.ncbi.nlm.nih.gov/33014208/
  5. Hamming, I et al. “Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.” The Journal of pathology
    vol. 203,2 (2004): 631-7. doi:10.1002/path.1570 https://pubmed.ncbi.nlm.nih.gov/15141377/
  6. Miranda, Kathryn et al. “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 vol. 10 1049. 10 May. 2019, doi:10.3389/fimmu.2019.01049 https://pubmed.ncbi.nlm.nih.gov/31134094/
  7. Anil, Seegehalli M et al. “Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages.” Scientific reports vol. 11,1 1462. 14 Jan. 2021, doi:10.1038/s41598-021-81049-2 https://pubmed.ncbi.nlm.nih.gov/33446817/
  8. Wauters, Els et al. “Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.” Cell research vol. 31,3 (2021): 272-290. doi:10.1038/s41422-020-00455-9 https://pubmed.ncbi.nlm.nih.gov/33473155/
  9. Nelson, Kathryn M et al. “The Essential Medicinal Chemistry of Cannabidiol (CBD).” 
    Journal of medicinal chemistry vol. 63,21 (2020): 12137-12155. doi:10.1021/acs.jmedchem.0c00724 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666069/
  10. Sido, Jessica M et al. “Marijuana-derived Δ-9-tetrahydrocannabinol suppresses Th1/Th17 cell-mediated delayed-type hypersensitivity through microRNA regulation.” Journal of molecular medicine (Berlin, Germany) vol. 94,9 (2016): 1039-51. doi:10.1007/s00109-016-1404-5 https://pubmed.ncbi.nlm.nih.gov/27038180/
  11. Sahin, Ugur et al. “COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses.”Nature vol. 586,7830 (2020): 594-599. doi:10.1038/s41586-020-2814-7 https://pubmed.ncbi.nlm.nih.gov/32998157/
  12. van Breemen, Richard B et al.“Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants.”Journal of natural products vol. 85,1 (2022): 176-184. doi:10.1021/acs.jnatprod.1c00946 https://pubmed.ncbi.nlm.nih.gov/35007072/
  13. Nguyen, Long Chi et al. “Cannabidiol Inhibits SARS-CoV-2 Replication and Promotes the Host Innate Immune Response.” bioRxiv : the preprint server for biology 2021.03.10.432967. 10 Mar. 2021, doi:10.1101/2021.03.10.432967. Preprint. https://pubmed.ncbi.nlm.nih.gov/33758843/
  14. Crippa, José Alexandre S et al. “Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.” Cannabis and cannabinoid research, 10.1089/can.2021.0093. 7 Oct. 2021, doi:10.1089/can.2021.0093 https://pubmed.ncbi.nlm.nih.gov/34619044/
  15. Vitetta, Luis et al. “Re: "Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial" by Crippa et al.” Cannabis and cannabinoid research, 10.1089/can.2022.0034. 1 Apr. 2022, doi:10.1089/can.2022.0034 https://doi.org/10.1089/can.2022.0034