COVID-19

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Prescription Advice

In case of COVID-19 infection, medical cannabis should be used only with a doctors prescription.

Summary

Summary

The use of cannabis for the treatment of COVID-19 is unknown and scientific literature is ambiguous on this topic.
On the one hand, cannabis compounds have an excellent track record as immunosuppressive agents and as such they have therapeutic potential to reduce inflammation and cytokine storm in case of COVID-19. However, on the other hand, the molecular actions of cannabinoids might actually make it easier for the virus to enter our cells and/or make COVID-19 infection to be more severe. Since this is pure scientific speculation and has not been directly tested, we advise to be cautious with the use of cannabis compounds with respect to COVID-19 and to consult a physician before either start or discontinue the use of medical cannabis.

Please, read the article we wrote for the scientific Journal of Cannabis Research in the following link https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00030-4

Statement

Due to the world situation we are experiencing regarding the spread of the COVID-19 disease, the GH Medical team would like to share with you the result of a quick but deep research we have done about the potential implications of cannabis use and COVID-19.

The coronavirus disease 2019 (COVID-19) is an infectious disease that is currently spreading all around the world causing a huge health and economic crisis. The pathogen of the disease, severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), is a recently identified coronavirus strain which causes a wide range of symptoms, including fever, cough, headache, muscle pain, sore throat, loss of smell and taste and shortness of breath. COVID-19 can develop into pneumonia, acute respiratory distress syndrome (ARDS), cytokine storm, septic shock and death.

The main route of transmission of COVID-19 is through the air, where droplets from an infected person travel to the nose, mouth or eyes of another person. Once the virus is inside the body, it enters into the cells causing the infection.

Scientists have discovered that COVID-19 enters into our body through a specific receptor located in our lungs. This receptor is called ACE-2 and is located specifically in the alveoli, which are responsible of the oxygen exchange to provide oxygen to our body. When the virus infects these cells, these cells starts to fail in their endeavor, compromising the full organism. The organism then reacts against the virus using the immune system, which needs to be healthy to work efficiently.

Even though there is no much research on how cannabinoids can affect this process, we have been reading most of the literature that is related to the mechanisms used by the virus and its potential link to cannabis use.

Our findings suggest that cannabis use probably does not represent any benefit in the case of COVID-19 infection. Any potential benefit derived from the use of cannabis in the case of the disease, does not represent any advantage compared to the recommended medication and guidelines from the World Health Organization. Our speculative scientific review of the literature suggests that cannabis use might increase the levels of ACE-2 receptors in our lungs. If that would be the case, the use of cannabis during a COVID-19 infection might not be advisable.

We want to highlight that there is not enough scientific evidence to support our findings on ACE-2 and cannabis use. We consider our findings scientific speculation. However, based on the existing scientific literature, we believe there is a possibility that this could be true. We believe that the therapeutic potential of cannabis during a COVID-19 infection does not outweigh the potential risk of its use.

We also want to point out two statements made by other science-based medical cannabis communities like the International Association of cannabinoid Medicines (IACM) or the Society of Cannabis Clinicians (SCC). These statements and/or research can be found in the following links:

IACM COVID-19 Statement  "there is no evidence that individual cannabinoids -- such as CBD, CBG or THC -- or cannabis preparations protect against infection with the SARS-CoV2 virus or could be used to treat Covid-19, the disease produced by this virus. Also, there is no evidence that the use of cannabinoids could increase the risk of viral infection"

SCC COVID-19 Statement "the antiviral action of specific cannabinoids have not been established to the extent that they should be recommended as a treatment option for COVID-19"

Finally, we want to highlight that the GH Medical team is made up of research scientists, we are not medical doctors. Hence, we do not recommend to take any action regarding cannabinoids or any other drug without asking your medical doctor.

Take care, stay home, stay safe.

The GH Medical team.

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Literature Discussion

(Full article can be found here: https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00030-4 )

ACE-2 receptor is used by SARS-CoV-2 as the entrance to infect human body  (Fang et al., 2020)

The Renin Angiotensin System (RAS) regulates blood pressure and has an important role on hypertension (Miller & Arnold, 2019)  

Antihypertensive drugs that inhibit either angiotensin converting enzymes (ACE) or angiotensin receptors, have been shown to lead to overexpression of ACE-2 (Fang et al., 2020)

The role of the overexpression of ACE-2 and the impact of antihypertensive drugs in the prognosis of COVID-19 infection is unknown (Cohen et al., 2020; Curfman, 2020; Fosbøl et al., 2020; Vaduganathan et al., 2020)

A retrospective cohort study showed no association between the use of these drugs and the diagnosis or mortality of COVID-19 infection.(Fosbøl et al., 2020)

Doctors advise patients who are already taking anti-hypertensive drugs to do not stop the medication (Vaduganathan et al., 2020)

The endocannabinoid system also regulates blood pressure and cannabinoids like THC and CBD induce hypotension (Pacher et al., 2018)

Hypotensive effects of cannabinoids are linked to CB1 activation (Pacher et al., 2018)

cannabinoids modulate angiotensin II (Stanley & O’Sullivan, 2014)

Hypotensive effects of hemp oil are mediated by ACE inhibition (Girgih et al., 2014; Orio et al., 2017)

CB1 and angiotensin II type 1 receptor (AT1R) form receptor heteromers, with lower expresion of CB1 and higher angiotensin II levels liked to hypertension (Haspula & Clark, 2016; Rozenfeld et al., 2011; Schaich et al., 2016)

CB1 activation reduces angiotensin II levels (Szekeres et al., 2012)

High-CBD cannabis extracts can modulate ACE-2 expression in artificial 3D human tissue models, suggesting a therapeutic potential in COVID-19 infection (Wang et al., 2020)

Preclinical evidence suggests cannabinoids might protect against cytokine storm and they could improve prognosis in the case of sepsis (Dinu et al., 2020)

CB2 receptor has been proposed as a therapeutic target to treat COVID-19 infection due to its modulation of pro-inflammatory cytokines (Rossi et al., 2020)

CBD has been proposed as a therapeutic agent to help the treatment of COVID-19 infection due to its anti-inflammatory properties and because its modulation of PPAR-y receptor could regulate fibroblast/myofibroblast activation and lead to inhibit pulmonary fibrosis (Esposito et al., 2020)

THC treatment reduced the immune system suppressing the cytokine storm in a mouse model of Acute Respiratory Distress Syndrome (ARDS) and increased their survival in 100%. The mechanisms involved the apoptosis of T-Cells after THC treatment and it was linked to mitochondrial pathways. The genes involved in these mechanisms share similarities with the ones found in pulmonary fluids from human COVID-19 patients (Mohammed et al., 2020). Please note these results come from animal models and not from an actual COVID-19 infection, clinical data is needed to assess its validity for patients.

A new study analyzed 40,000 genes from 17,000 pulmonary fluid samples obtained from COVID-19 patients and found a RAS imbalance when compared to controls. Key related genes to ACE, ACE-2 and other RAS proteins were modulated in COVID-19 patients, supporting the bradykinin hypothesis of which upregulated bradykinin peptide might be the cause of many pulmonary signs and symptoms associated to COVID-19. Specifically, ACE, which degrades bradykinin, shows to be downregulated while ACE-2, which enhances bradykinin, is upregulated (Garvin et al., 2020). Since cannabinoids target the RAS, it is very important to understand how cannabinoids can modulate the biological mechanisms underlying a COVID-19 infection.

 

References

Cohen JB, Hanff TC, Bress AP, South AM. Relationship Between ACE2 and Other Components of the Renin-Angiotensin System. Curr Hypertens Rep. 2020 Jun 26;22(7):44.

Curfman G. Renin-Angiotensin-Aldosterone Inhibitors and Susceptibility to and Severity of COVID-19. JAMA. 2020 Jul 14;324(2):177–8.

Dinu AR, Rogobete AF, Bratu T, Popovici SE, Bedreag OH, Papurica M, et al. Cannabis Sativa Revisited-Crosstalk between microRNA Expression, Inflammation, Oxidative Stress, and endocannabinoid Response System in Critically Ill Patients with Sepsis. Cells. 2020 Jan 28;9(2).

Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of Underlying Diseases in Hospitalized Patients with COVID-19: a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2020;8(1):e35.

Erdös EG. Conversion of angiotensin I to angiotensin II. Am J Med. 1976 May 31;60(6):749–59.

Esposito, G., Pesce, M., Seguella, L., Sanseverino, W., Lu, J., Corpetti, C., & Sarnelli, G. (2020). The potential of cannabidiol in the COVID-19 pandemic. British Journal of Pharmacology. https://doi.org/10.1111/bph.15157

Fang L, Karakiulakis G, Roth M. Are patients with hypertension and Diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Mar 11;

Fosbøl EL, Butt JH, Østergaard L, Andersson C, Selmer C, Kragholm K, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA. 2020 Jul 14;324(2):168–77.

Garvin, M. R., Alvarez, C., Miller, J. I., Prates, E. T., Walker, A. M., Amos, B. K., Mast, A. E., Justice, A., Aronow, B., & Jacobson, D. (2020). A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. ELife, 9, e59177. https://doi.org/10.7554/eLife.59177

Girgih AT, Alashi A, He R, Malomo S, Aluko RE. Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats. Eur J Nutr. 2014 Aug;53(5):1237–46.

Haspula D, Clark MA. Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats. J Neurochem. 2016;139(4):523–36.

Miller AJ, Arnold AC. The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications. Clin Auton Res Off J Clin Auton Res Soc. 2019;29(2):231–43.

Mohammed, A., F K Alghetaa, H., Miranda, K., Wilson, K., P Singh, N., Cai, G., Putluri, N., Nagarkatti, P., & Nagarkatti, M. (2020). Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression. International Journal of Molecular Sciences, 21(17). https://doi.org/10.3390/ijms21176244

Orio LP, Boschin G, Recca T, Morelli CF, Ragona L, Francescato P, et al. New ACE-Inhibitory Peptides from Hemp Seed (Cannabis sativa L.) Proteins. J Agric Food Chem. 2017 Dec 6;65(48):10482–8.

Pacher P, Steffens S, Haskó G, Schindler TH, Kunos G. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol. 2018;15(3):151–66.

Rossi, F., Tortora, C., Argenziano, M., Di Paola, A., & Punzo, F. (2020). cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection? International Journal of Molecular Sciences, 21(11), 3809. https://doi.org/10.3390/ijms21113809

Rozenfeld R, Gupta A, Gagnidze K, Lim MP, Gomes I, Lee-Ramos D, et al. AT1R-CB₁R heteromerization reveals a new mechanism for the pathogenic properties of angiotensin II. EMBO J. 2011 May 3;30(12):2350–63.

Schaich CL, Grabenauer M, Thomas BF, Shaltout HA, Gallagher PE, Howlett AC, et al. Medullary endocannabinoids Contribute to the Differential Resting Baroreflex Sensitivity in Rats with Altered Brain Renin-Angiotensin System Expression. Front Physiol. 2016;7:207.

Sexton M. Cannabis in the Time of Coronavirus Disease 2019: The Yin and Yang of the endocannabinoid System in Immunocompetence. J Altern Complement Med. 2020 May 7;26(6):444–8.

Stanley C, O’Sullivan SE. Vascular targets for cannabinoids: animal and human studies. Br J Pharmacol. 2014 Mar;171(6):1361–78.

Szekeres M, Nádasy GL, Turu G, Soltész-Katona E, Tóth ZE, Balla A, et al. Angiotensin II induces vascular endocannabinoid release, which attenuates its vasoconstrictor effect via CB1 cannabinoid receptors. J Biol Chem. 2012 Sep 7;287(37):31540–50.

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med. 2020 23;382(17):1653–9.

Wang B, Kovalchuk A, Li D, Ilnytskyy Y, Kovalchuk I, Kovalchuk O. In Search of Preventative Strategies: Novel Anti-Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues. 2020 Apr 19 [cited 2020 Apr 27]; Available from: https://www.preprints.org/manuscript/202004.0315/v1

Clinical Trials

OEA has anti-inflammatory, antioxidant and immunomudolatory properties and it is being tested in clinical trials as adjuvant treatment for COVID-19 infection (Ghaffari et al., 2020)

References

Ghaffari, S., Roshanravan, N., Tutunchi, H., Ostadrahimi, A., Pouraghaei, M., & Kafil, B. (2020). Oleoylethanolamide, A Bioactive Lipid Amide, as A Promising Treatment Strategy for Coronavirus/COVID-19. Archives of Medical Research, 51(5), 464–467. https://doi.org/10.1016/j.arcmed.2020.04.006