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Cannabidiol (CBD) and COVID

Mark T. Hamann, PhD
Professor of Drug Discovery & Biomedical Sciences and Public Health
Medical University of South Carolina

Background

The Cannabis sativa plant. The hemp or Cannabis sativa plant has been used in traditional medicine and religious ceremonies since the beginning of recorded history.  The Native Americans used the plant as a stimulant to promote recovery from a number of diseases and ailments.  These early strains of hemp were not selected yet for THC production, which only occurred in the last half-century. As a result, the recorded benefits of Cannabis by the Native Americans and other traditional plant-based medicines would have been at least in part due to CBD content.  In 2018 the FDA approved the use of CBD (Epidiolex) for the control of epileptic seizures associated with Dravet & Lennox-Gastaut syndrome and tuberous sclerosis complex. The recommended dose titration begins at 5mg/kg/day and increases weekly by 5mg/kg/day until a max dosage of 25mg/kg/day. Thus, a 50kg individual would begin with 250mgs/day of CBD and increase to a max dose of 1.2 grams of CBD per day/50kg.  Clinical studies for the control of movement disorders, anxiety, cognitive function, and pain have been reported but, in this summary, we are primarily focused on the control of COVID19 or SARS-CoV2.

The data reviewed below has NOT yet resulted in FDA approval for the use of cannabinoids as drug products for COVID19.  Please consult and review these data with your healthcare provider to determine if CBD offers any benefits for you personally.

CBD and COVID

In 2022 a group called the “National COVID Cohort Collaborative Consortium” published a highly encouraging report revealing a strong link between CBD use and reduced risk of developing COVID19 entitled: “Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune response”(Nguyen, Yang et al. 2022)PubMed (nih.gov). This report reveals an EC50 of 0.6-1.8 mM against spike-positive cells and consistent inhibition regardless of which SARS-CoV2 variant is evaluated.  This type of immune response is similar to the reaction of urushiol, the active molecule of poison ivy, and proteins in the skin.  Poison ivy elicits a very aggressive immune system response against human cells resulting in inflammation and itching.  CBD elicits the same type of aggressive immune response against the SARS-CoV-2 virus due to interactions between CBD and spike proteins at the surface of the virus.  In a separate study, it has been shown that cannabinoids block viral entry, including different variants into cells(van Breemen, Muchiri et al. 2022).

Link:Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants – PubMed (nih.gov).

CBD is metabolized by a P450 enzyme to 7-OH-CBD, which is active in reducing spike protein positive cells.  CBD was shown to reduce lung and nasal viral concentrations of SARS-CoV-2 infected mice.  Perhaps of greatest significance was that in a national sampling of patients using CBD products with a 100mg/mL concentration; there was a significant reduction of COVID positive patients relative to a population not using CBD. The figure below is taken from the (Nguyen, Yang et al. 2022) publication. It reveals that patients taking FDA-approved CBD only tested positive 1% of the time vs matched controls not using CBD testing positive 12% of the time.   This is a very dramatic reduction in COVID-19 positive tests. While the FDA may have not yet approved CBD for this application; the National Institutes of Health does provide an easy-to-read summary of this report which is highly glowing of this study.

Link: Early Studies Suggest CBD May Help Prevent COVID-19 | NIH COVID-19 Research

In Summary, here are the take-home messages relating to CBD and Covid:

  • Patients who use CBD at the dosage recommended by the FDA for epilepsy have an order-of-magnitude drop in COVID-19 positive tests.  CBD users are positive 1% of the time vs 12% for non-users.
  • The metabolic product of CBD called 7-OH-CBD remains active against the virus.
  • CBD provides multiple mechanisms for inhibiting SARS-CoV2 replication but the most profound is the initiation of the innate immune system.
  • CBD has a long half-life thus missing a daily dose or taking CBD infrequently will still provide protection
  • CBD is active against all SARS-CoV2 variants tested thus far.
  • While the mortality rate associated with COVID-19 has dropped considerably there were over 70,000 deaths in 2023 making it a major cause of mortality in the US.  
  • CBD may also prove useful in the control of MERS and SARS and further testing against cold, flu and RSV is highly warranted.  
  • CBD is readily available without a prescription and is relatively free of side effects.
  • CBD should not be used with other cannabinoids for maximum effectiveness against the virus.
  • CBD should not be used as a replacement for vaccinations at this stage.
  • While CBD is not FDA-approved for the control of viruses, the data presented here is highly convincing that CBD does indeed control viral replication in laboratory, animal, and human models.
  • The safety of CBD is very high and it has a long history of human exposure thus the benefit-risk assessment for the control of COVID19 has attracted considerable attention including the National Institutes of Health.

CBD and Inflammation

Although the FDA has yet to approve CBD as an anti-inflammatory agent; there is a growing volume of data in animal and human clinical trials for the potential benefits suggesting that approval at some point in the future is likely. Inflammation is a significant contributing factor to a number of diseases, including SARS-CoV-2, cancer, heart disease, arthritis, Crohn’s disease, and many others.  Thus, controlling chronic inflammation is an important strategy for promoting wellness and health and reducing the risk of a number of chronic diseases.   Osteoarthritis (OA).  OA is a multifactorial disease involving inflammation, joint degeneration, and peripheral neuropathy.  In a study in rats, the prophylactic treatment with CBD prevented the development of pain and nerve damage in OA joints.  These studies suggest that CBD may be a safe treatment for OA-induced neuropathic pain.(Philpott, OʼBrien et al. 2017).  This is significant as the CDC indicates 32.5 million Americans suffer from OA and an individual over the age of 60 suffers from at least some degree of OA.

Potential side-effects of CBD

The side effects of CBD are relatively mild compared to most drugs and botanical products.  These include drowsiness, diarrhea, irritability, interactions with other drugs, and, with prolonged and high dosages, liver damage is possible. Like many drugs, CBD is not recommended during pregnancy.

Link:  CBD: What You Need to Know (cdc.gov) 

What is the best time to take CBD?

Based on the available data, the dosage and time of administration have a significant impact on the outcome of the application.  This is due to the odd observation U shaped dose-response effects in which low doses of CBD (25-50mgs) promote wakefulness and higher dosages (>150mgs) promote sleep.  Thus, if you plan on taking 150mgs or more of CBD to control COVID19, inflammation, pain, anxiety or promote sleep the product should be administered shortly before bedtime.  Lower doses of 25-50mgs will promote wakefulness and should be used in the morning or early afternoon.

What is the purest form of CBD?

CBD isolate is a pure >98% pharmaceutical-grade product that is generated through crystallization.  This material is a waxy solid and is typically diluted in an oil to facilitate oral administration.  Sycamore BioPharma utilizes freshly pressed hempseed oil as a diluent as hempseed oil is the plant source with the highest omega-3 fatty acid content thus providing a source of heart-healthy Omega-3 oils in addition to the CBD content.

Safety

(Wang 2021)  Cannabis (marijuana): Acute intoxication – UpToDateAlthough deaths associated with cannabinoid use are few, if any, there has been a significant increase in cannabinoid overdose in children.  Toxic overdoses associated with cannabinoids have been primarily limited to THC and using THC with CBD will antagonize the activity as a control for COVID19.  Thus, the use of THC with CBD for the control of SARS-CoV-2 is not recommended.

Future FDA Studies

Based on the very compelling recent reports of CBD as a control of viral replication; it seems prudent that the FDA plan to support and initiate research to: 

  • Evaluate the use of market-research data and other data sources that provide insights into the use of specific CBD products in different populations. 
  • Evaluate the use of data linkage approaches to provide insights about safety risks that may appear across time while protecting the privacy of patients and consumers.

 

Link: Better Data for a Better Understanding of the Use and Safety Profile of Cannabidiol (CBD) Products | FDA

REFERENCES

  • Bergamaschi, M. M., R. H. Queiroz, M. H. Chagas, D. C. de Oliveira, B. S. De Martinis, F. Kapczinski, J. Quevedo, R. Roesler, N. Schröder, A. E. Nardi, R. Martín-Santos, J. E. Hallak, A. W. Zuardi and J. A. Crippa (2011). “Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients.” Neuropsychopharmacology 36(6): 1219-1226.
  • Nguyen, L. C., D. Yang, V. Nicolaescu, T. J. Best, H. Gula, D. Saxena, J. D. Gabbard, S. N. Chen, T. Ohtsuki, J. B. Friesen, N. Drayman, A. Mohamed, C. Dann, D. Silva, L. Robinson-Mailman, A. Valdespino, L. Stock, E. Suárez, K. A. Jones, S. A. Azizi, J. K. Demarco, W. E. Severson, C. D. Anderson, J. M. Millis, B. C. Dickinson, S. Tay, S. A. Oakes, G. F. Pauli, K. E. Palmer, D. O. Meltzer, G. Randall and M. R. Rosner (2022). “Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses.” Sci Adv 8(8): eabi6110.
  • Philpott, H. T., M. OʼBrien and J. J. McDougall (2017). “Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.” Pain 158(12): 2442-2451.
  • van Breemen, R. B., R. N. Muchiri, T. A. Bates, J. B. Weinstein, H. C. Leier, S. Farley and F. G. Tafesse (2022). “Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants.” J Nat Prod 85(1): 176-184.
  • Wang, G. S. (2021). “Cannabis (marijuana): Acute intoxication.” UpToDate.
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