A year into Covid-19 and no governing health organization has established a task force to study pre-existing medications in the prevention of Covid-19, according to Dr. Pierre Kory‘s testimony at a US Senate meeting. An anti-parasitic drug, Ivermectin, has shown unproven but ‘miraculous‘ results in large doses that are now accepted by many physicians. Despite positive clinical trials, a lack of negative studies, and its forty years of use, Ivermectin still cannot be suggested for coronaviruses. So, do any drugs work, is a natural remedy like cannabis an antiviral for Covid-19?
PPARs and a druggable pocket?
We previously mentioned a special receptor triggered by cannabis that might affect Covid-19 via complicated immune support. The receptor in question is known as PPAR-y. This is a crucial mechanism for the function of many biological systems and is safely activated by certain botanical components. Despite this, any attempt to develop a pharmaceutical formulation has so far caused complications.
This druggable receptor has been the focus of many studies on Covid-19 treatments since our initial discussion at the beginning of the pandemic. Further discoveries have included a new druggable pocket within Sars-Cov2. This pathway is centered around a common fat component utilized in many biological functions known as linoleic acid, which is heavily depleted by the virus.
This fatty acid helps increase PPAR-y signaling which in turn can regulate lipid homeostasis. So, the devastation caused by Covid-19 is also partly related to the depletion of PPAR activity. Thankfully though, the druggable receptor can be activated by certain antiviral cannabinoids in cannabis which will affect Covid-19 by stopping a deadly cycle.
- THCa and CBGa (oral), CBG, and CBD are PPAR-y agonists. As well as components of chocolate, maca root, pomegranate, thyme, oregano, hot pepper, rosemary, sage, lemongrass, Omega fats, and soybean.
Grand Unified Theory (G.U.T.): The Endocannabinoid System, cannabis, and the Microbiome – Russo. E.B., MD, Cannamed, 2018
Protein inhibiting flavonoids
Lopinavir/ritonavir is an antiviral drug that went through trial testing against Covid-19 but was deemed ineffective against severe cases on its own. There is still some mild effect against Sars-Cov2 that, given minimal side effects, should not be overlooked in nature’s broader profile – enter cannabis.
Lopinavir/ritonavir‘s effects on the immune system can be partially supplemented by cannabinoids by activating PPAR-y. Yet, the antiviral drug combination, as well as hydroxychloroquine, also blocks the spike protein that Sars-Cov2 uses to bind to human receptor sites. They do this by acting as antinutrients. Cannabinoids, quercetin, and other flavonoids found in certain cannabis strains are equally as effective as antiviral drugs for Covid-19 in this regard. The problem with utilizing antinutrients in disease therapy is their low oral bioavailability, hence the importance of zinc and Vitamins, D and C. But, even with good absorption, they can only partially block the virus since Sars-Cov2 allegedly has a secondary binding site that can surpass these specific drugs.
- Certain flavonoids are as effective as lopinavir and more effective than hydroxychloroquine against Sars-Cov2’s S protein.
- These flavonoids can be found in, but not limited to, cannabis, spinach, green olives, and citrus fruits.
Cannabinoid 1 receptor, Phyptecs, 2015
Cannabis, cytokine storms, and immunity
The University of Lethbridge found a small number of mostly CBD-dominant strains that might reduce two key cytokines involved in Covid-19’s lethal storm. Furthermore, CB2 receptor agonists, such as caryophyllene, can support our immunity as well as Covid-19 antibody production.
A warning though, excessive cannabis consumption does have the potential to suppress the immune system which can negatively affect Covid-19. As an example, CBD can inhibit ACE-2 which is a receptor that the virus binds to and severely depletes. So, theories suggest that an ACE-2 inhibitor can increase Covid-19 severity. Although, the drug’s effect is indeed neutral according to further trials and epidemiological evidence.
- CB2 receptor agonists in cannabis help produce an antiviral antibody, IgM, to fight Covid-19 by intelligently controlling B cells.
- Chronic cannabis use can suppress a key cytokine in many lethal Covid-19 cases.
Do you experience a stronger or weaker immune system after using cannabis? Let us know in the comments and stay tuned to learn how cannabis and packaged food can affect Covid-19 through our gut bacteria.
- Attia, Y. A., Alagawany, M. M., Farag, M. R., Alkhatib, F. M., Khafaga, A. F., Abdel-Moneim, A. E., Asiry, K. A., Mesalam, N. M., Shafi, M. E., Al-Harthi, M. A., & Abd El-Hack, M. E. (2020). Phytogenic Products and Phytochemicals as a Candidate Strategy to Improve Tolerance to Coronavirus. Frontiers in veterinary science, 7, 573159. doi.org/10.3389/fvets.2020.573159
- Cabral, G. A., & Griffin-Thomas, L. (2008). Cannabinoids as therapeutic agents for ablating neuroinflammatory disease. Endocrine, metabolic & immune disorders drug targets, 8(3), 159–172. doi.org/10.2174/187153008785700118
- Ciavarella, C., Motta, I., Valente, S., & Pasquinelli, G. (2020). Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease. Molecules (Basel, Switzerland), 25(9), 2076. doi.org/10.3390/molecules25092076
- Hung, I. F., Lung, K. C., Tso, E. Y., Liu, R., Chung, T. W., Chu, M. Y., Ng, Y. Y., Lo, J., Chan, J., Tam, A. R., Shum, H. P., Chan, V., Wu, A. K., Sin, K. M., Leung, W. S., Law, W. L., Lung, D. C., Sin, S., Yeung, P., Yip, C. C., … Yuen, K. Y. (2020). Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet (London, England), 395(10238), 1695–1704. doi.org/10.1016/S0140-6736(20)31042-4
- Keen, L., 2nd, Abbate, A., Blanden, G., Priddie, C., Moeller, F. G., & Rathore, M. (2017). Confirmed marijuana use and lymphocyte count in black people living with HIV. Drug and alcohol dependence, 180, 22–25. doi.org/10.1016/j.drugalcdep.2017.07.026 (Retraction published Drug Alcohol Depend. 2019 May 1;198:199)
- Keen, L., 2nd, Pereira, D., & Latimer, W. (2014). Self-reported lifetime marijuana use and interleukin-6 levels in middle-aged African Americans. Drug and alcohol dependence, 140, 156–160. doi.org/10.1016/j.drugalcdep.
- Lüdtke, A., Buettner, J., Schmidt, H. H., & Worman, H. J. (2007). New PPARG mutation leads to lipodystrophy and loss of protein function that is partially restored by a synthetic ligand. Journal of medical genetics, 44(9), e88. doi.org/10.1136/jmg.2007.050567
- MacCallum, C. A., & Russo, E. B. (2018). Practical considerations in medical cannabis administration and dosing. European journal of internal medicine, 49, 12–19. doi.org/10.1016/j.ejim.2018.01.004
- Meini, S., Pagotto, A., Longo, B., Vendramin, I., Pecori, D., & Tascini, C. (2020). Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives. Journal of clinical medicine, 9(7), 2050. doi.org/10.3390/jcm9072050
- Russo E. B. (2018). Cannabis Therapeutics and the Future of Neurology. Frontiers in integrative neuroscience, 12, 51. doi.org/10.3389/fnint.2018.00051
- Russo, M., Moccia, S., Spagnuolo, C., Tedesco, I., & Russo, G. L. (2020). Roles of flavonoids against coronavirus infection. Chemico-biological interactions,328, 109211. doi.org/10.1016/j.cbi.2020.109211