A Storm of Research Activity into Cannabis and Coronavirus A Closer Look at Expanding Research of Cannabinoids and Terpenes in COVID-19

There has been a recent flurry of scientific manuscripts and articles published on the topic of potential applications of cannabinoids and terpenes for coronavirus prevention or treatment of symptoms. This spike in research into cannabis and COVID-19 gives us hope for future treatments and paves the way for future medicinal cannabis research.

In this installment of "Cannabis Crossroads," I review a handful of recent articles related to COVID-19 and cannabis. I also spoke with a top medical cannabis expert—Dr. Prakash Nagarkatti, Vice President for Research at the University of South Carolina (USC)—to get a better sense for where future research efforts are heading. Dr. Nagarkatti has recently shown that tetrahydrocannabinol (THC) can prevent the development of colitis-associated colon cancer in mice (1). Under his leadership and guidance USC has patented a US Food and Drug Administration (FDA)-approved process for treating autoimmune hepatitis with cannabidiol (CBD) derived from hemp (2).

Current Research

Dr. Dedi Meiri, world-renown cannabis expert at the Israel Institute of Technology and Chairman and CSO of the company CannaSoul, recently announced that his laboratory was “approved to operate as a corona lab” and that they are investigating novel antiviral terpene formulations that can potentially suppress the immune response to COVID-19 (3,4). Dr. Meiri is also researching compounds contained in cannabis as potential treatments for viral infections via modulation of cytokine storms, severe immune reactions in which the body releases excessive cytokines into the blood too rapidly.

Cytokines play an important role in normal immune responses, but a large amount of them released in the body too quickly can be harmful. Signs and symptoms of a cytokine storm include high fever, inflammation (redness and swelling), and severe fatigue and nausea (5). COVID-19 is especially fatal when patients experience cytokine storms (6). There are extreme challenges associated with treating severe COVID-19 patients and this research exploring applications of cannabinoids to treat cytokine storms may provide additional options to medical caregivers.

Another recent study published in the journal Cannabis and Cannabinoid Research by researchers at the Dental College of Georgia and Medical College of Georgia (7) also shows that CBD could help with COVID-19 patients with severe respiratory distress and could potentially obviate the need for mechanical ventilators. The authors note that, “among all cannabinoids, cannabidiol (CBD) has demonstrated potent anti-inflammatory effects in a variety of pathological conditions. Therefore, it is logical to explore whether CBD can reduce the cytokine storm and treat ARDS.”

The authors conclude that their results “suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.”

Ask an Expert

Thank you for joining me to discuss potential cannabis applications in coronavirus research, Dr. Nagarkatti. Could you please tell us about your laboratory and research focus at USC?

Dr. Prakash Nagarkatti: Our laboratory is located at the University of South Carolina in Columbia, South Carolina. My primary research interests are in the areas of inflammation. We are looking at how botanicals suppress inflammation. One of the projects we are working on is how cannabinoids suppress inflammation and cancer. We have been pursuing this research for more than 20 years. Our research is funded by the National Institutes of Health (NIH). 

Please summarize the results of your recent work related to the cytokine storm that is associated with COVID-19 and help our readers understand why this is important.

Dr. Nagarkatti: Our recent research has shown that THC found in cannabis can suppress acute respiratory distress syndrome (ARDS) and cytokine storm induced by a bacterial toxin, Staphylococcal enterotoxin B. This toxin can cause ARDS in humans as well as animals. In mice, this toxin can trigger ARDS and cytokine storm resulting in respiratory and multi-organ failure and the mice dying in less than 5 days. In this model, we found that THC can completely prevent ARDS, cytokine storm, and mortality. Because this ARDS is similar to that seen in COVID-19 patients who develop ARDS, our data suggest that THC may be effective against severe forms of COVID-19 that leads to ARDS, cytokine storm, and high percentage of mortality. It should be noted that ARDS kills almost 40% of patients and currently there is no FDA approved drug to treat this disease.

I would like to caution that our data should not be interpreted to suggest that cannabis is good to prevent COVID-19 infection. Our results only suggest that it is good to treat the severe form of COVID-19 in which, due to ARDS and cytokine storm, a significant proportion of patients die.

Cannabis is not one single medicine—each chemovar has a unique cannabinoid and terpenoid fingerprint. Which cannabinoids were researched in your article? Can you speak to which types of cannabis or cannabinoids seem to have the greatest benefits for viral infections?

Dr. Nagarkatti: We worked on THC. We have not done any studies to see if cannabinoids can prevent viral replication. 

What biochemical pathways do cannabinoids appear to be influencing that may result in either protection from infection or potential therapeutic benefits?

Dr. Nagarkatti: Cannabinoids such as THC suppress inflammation through a variety of mechanisms. They induce T cells that suppress inflammation called regulatory T cells. They also induce microRNA that trigger cytokines such as IL-10 and TGF-b that are immunosuppressive. The microRNA can also induce the generation of other types of cells that suppress inflammation called myeloid-derived suppressor cells.

Are there any potential negative effects of cannabis use that might put a person at greater risk for COVID-19 infection or exacerbate symptoms?

Dr. Nagarkatti: Yes, a high dose of cannabinoids may overtly suppress the immune response, which may make a normal individual more susceptible to COVID-19 infection, although studies need to be performed to see if this is true at the population level. 

What future studies related to cannabinoids is your laboratory interested in?

Dr. Nagarkatti: We are interested in using cannabinoids such as THC and CBD to treat inflammatory and autoimmune diseases and cancer. Our work on the use of CBD to treat autoimmune hepatitis has been recognized by the FDA and the FDA has approved the use of CBD to treat autoimmune hepatitis as an orphan drug. 

We just published a paper showing THC attenuates inflammation in the colon and thereby prevents colon cancer (8).

Any closing thoughts on the topics of cannabinoids, terpenes, or other cannabis components that appear to be worth investigating in future studies?

Dr. Nagarkatti: Cannabis has more than 100 cannabinoids of which only two (THC and CBD) have been well studied. Thus, there is plenty of opportunity to explore all others.

Conclusion

In closing, I would like to highlight that the work described above is scientific research and further studies are needed to better understand the full potential of cannabinoids (and terpenes) for treating coronavirus. The FDA has, in fact, issued several warning letters to CBD companies for selling fraudulent products with claims to prevent, treat, mitigate, diagnose, or cure COVID-19 (9,10). The contents of this article are intended for informational and educational purposes only and not for the purpose of rendering medical advice. The contents of this article and the manuscripts referenced herein are not intended to substitute for professional medical advice, diagnosis, or treatment. Please consult your physician for personalized medical advice. Always seek the advice of a physician or other qualified healthcare provider with any questions regarding a medical condition.

Please remember to take care of yourself and your loved ones. Remember that we’re all in this together.

References

1. Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production, Published in iScience, Volume 23, Issue 9, 25 September 2020, 101504. https://doi.org/10.1016/j.isci.2020.101504​
2. US Patent #8,242,178, August 14, 2012, Use of cannabidiol in the treatment of autoimmune hepatitis.
3. ​https://www.technion.ac.il/en/home-2/.
4. “Could cannabis terpene formulation treat COVID-19?”, Medical Cannabis Network, 27th April 2020, https://www.healtheuropa.eu/cannabis-terpene-formulation-treat-covid-19/99586/.
5. National Institutes of Health (NIH) National Cancer Institutes (NCI) Dictionary of Cancer Terms website at https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cytokine-storm.
6. “The coronavirus turns deadly when it leads to ‘cytokine storm’; identifying this immune response is key to patient’s survival: report” article updated Mar 13, 2020; Posted Mar 13, 2020 in OregonLive.com at: https://www.oregonlive.com/coronavirus/2020/03/the-coronavirus-turns-deadly-when-it-leads-to-cytokine-storm-identifying-this-immune-response-is-key-to-patients-survival-report.html.
7. Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA, Cannabis and Cannabinoid Research, Vol. 5, No. 3, https://www.liebertpub.com/doi/abs/10.1089/can.2020.0043.
8. https://pubmed.ncbi.nlm.nih.gov/32942172/.
9. https://www.fda.gov/consumers/health-fraud-scams/fraudulent-coronavirus-disease-2019-covid-19-products#Warning%20Letter%20Table.
10. FDA Warning letters for unauthorized or misbranded products: https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters.

About the Interviewee

Prakash Nagarkatti, PhD, Vice President for Research, USC

Dr. Nagarkatti joined the University of South Carolina (USC) in 2005 and currently serves as Vice President for Research (VPR) and Carolina Distinguished Professor. In his role as VPR at USC, he oversees research enterprise of ~$280 million at the main campus located in Columbia as well as seven satellite campuses, located throughout the state. He received his PhD in immunology. Prior to joining USC, he was a faculty member at Virginia Tech and at the Medical College of Virginia. 

In addition to administration, Dr. Nagarkatti is actively engaged in research. He currently directs three federally-funded research centers: Two of them are funded by NIH and the third is funded by NSF, which together, have generated more than $82 million in the past ~12 years. Dr. Nagarkatti has generated more than $100 million in research funding as PI since moving to USC in 2005.
He has published ~300 peer-reviewed papers. He has mentored ~40 graduate students, 24 post-doctoral fellows, and 20 junior faculty as well as 35 International Scholars. For his outstanding contributions to science, Dr. Nagarkatti was elected Fellow of American Association for the Advancement of Science (AAAS), Fellow of Academy of Toxicological Sciences (ATS), and a Fellow of the National Academy of Inventors. He has been the recipient of the Vos Lifetime Career Achievement Award from the Society of Toxicology (SOT). His laboratory’s patent on cannabidiol
to treat autoimmune hepatitis was licensed to Revive Therapeutics and has been approved by FDA. 

Dr. Nagarkatti has served and continues to serve on numerous national panels including National EPSCoR/IDeA Coalition Board, EPA, and FDA. He has chaired numerous NIH Study Sections for NCCIH and NIGMS. He was also invited to serve on FDA Panel of Expert Working Group on Drug-induced Vascular Injury. Dr. Nagarkatti has organized the 26th NSF EPSCoR National Conference
in Columbia, SC. 

ABOUT THE COLUMNIST

Joshua Crossney is the columnist and editor of “Cannabis Crossroads” and a contributing editor to Cannabis Science and Technology magazine. Crossney is also the president and CEO of CSC Events.
Direct correspondence to:
Josh@CannabisScienceConference.com​

How to Cite this Article

J. Crossney, Cannabis Science and Technology 3(8), 34-36 (2020).