By Luke Sumpter

The COVID-19 pandemic has completely upended most of our lives. The subsequent lockdowns ravaged the economy, cut us off from friends and family, and even changed the way we work. Although things are slowly returning to normal, we’re still living in uncertain times. Will vaccines and up-and-coming therapeutics help us develop herd immunity and stomp the virus out of existence? Or will the constant emergence of new variants mean we will have to learn to live with the pathogen?

Regardless of the long-term outcomes, scientists are hunting for therapeutics that might help patients overcome instances of infection. Currently, medical professionals have an arsenal[1] of interventions to choose from, including antivirals, monoclonal antibodies, blood thinners, and convalescent plasma.

Now, researchers are turning their attention to cannabis as a potential source of COVID-19 therapeutics. The cannabis plant produces hundreds of phytochemicals, and some of them have garnered the interest of scientists due to the ways in which they impact the immune system.

Join us as we explore how the virus works, the symptoms of the disease it causes, and how the endocannabinoid system and cannabis might play a role in future coronavirus treatments.

SARS-CoV-2: The Source of the Chaos

The exact origins of SARS-CoV-2 are still up for debate[2]. Regardless of whether it emerged from human tampering or as a zoonotic virus in nature, we do know that the pathogen causes a potentially fatal disease known as COVID-19. After first showing up in the Chinese city of Wuhan, the virus soon spread to almost every country on Earth.

How SARS-CoV-2 Infects the Body

So, how does the virus infect the body in the first place? We’ve all seen images of the crown-like pathogen by now. The virus features an external spherical envelope dotted with spike proteins. Inside this ball exists a single strand of RNA—a piece of biological code capable of creating proteins in the body.

When the virus passes through the upper respiratory tract and into the lungs, it uses the spike proteins to latch onto binding sites on lung cells called ACE2 receptors[3]. After it docks, the envelope releases the RNA strand into the host cell. Here, the piece of code hijacks the cell's protein-forming apparatus to make copies of itself. These newly created viral particles then leave the host cell in search of other cells to infect, fuelling the replication process.

Symptoms of COVID-19

After exposure to SARS-CoV-2, a person becomes at risk of developing the disease it causes: COVID-19. This illness ranges in severity depending on several factors, including age and underlying health conditions. Some people experience no symptoms at all. Others experience only mild symptoms, whereas some patients endure severe cases of the illness. The initial symptoms of COVID-19 typically develop over 2–14 days, and include:

Shortness of breath Fever
Fatigue Loss of taste and smell
Persistent cough Chest pain and tightness

Approximately 80% of people[4] make a full recovery after a brief bout of these symptoms. However, the remaining 20% experience more severe cases of the disease. These more intense symptoms include:

Difficulty breathing Fluid buildup in the lungs
Lung injury Pneumonia

The virus can also migrate to other areas of the body and cause damage to other organs and systems, such as the:

Kidneys Nervous system
Gastrointestinal system Cardiovascular system

The Cytokine Storm

The most severe cases of COVID-19 stem from an overly aggressive immune system reaction[5]. When the virus infects a lung cell, the infected cell sends out a signal to recruit a large number of white blood cells—members of the immune system that fight off intruders. These tiny soldiers then release chemicals called inflammatory cytokines that work to attract more white blood cells to the site of infection, creating a positive feedback loop.

Although this mechanism serves to protect the body against the virus, the immune system sometimes overshoots the mark, resulting in a state of hyperinflammation. The buildup of inflammatory cytokines sometimes causes a “cytokine storm”, which can lead to acute respiratory distress syndrome (ARDS). Patients experience shortness of breath as fluid accumulates up in the lungs. When things get really bad, this reaction can cause lung failure that may require ventilation.

The Cytokine Storm

The Role of the Endocannabinoid System in Immunity

So, where does cannabis fit into all of this? To figure this out, we first need to explore how cannabis works in the body. The plant contains hundreds of molecules of interest. The two main classes of phytochemicals found within the flowers are cannabinoids and terpenes.

It just so happens that cannabinoids, including THC and CBD, work in a very specific way in the human body. They interface with a body-wide regulatory network called the endocannabinoid system (ECS). This system consists of receptors, signalling molecules, and enzymes found all over the body. They show up in the nervous system, immune system, digestive system, and beyond.

The ECS doesn’t show up everywhere by accident. The system serves as a universal regulator in the body that helps to keep everything balanced and running smoothly. It governs an incredible amount of processes, including neurotransmitter firing, appetite, and immune response.

Our own internal cannabinoids, known as endocannabinoids, are responsible for keeping this system running properly. They bind to cannabinoid receptors and create the necessary changes inside target cells. Amazingly, phytocannabinoids (those derived from plants) share a similar molecular structure to our endocannabinoids. This enables them to bind to the same receptors and create similar changes to our physiology.

Because the ECS plays a key role in immunity, some cannabinoids might help to modulate the immune response. The system consists of two main receptor types, namely CB1 and CB2. The latter occurs abundantly throughout the immune system[6] and exists in various white blood cells, as well as the spleen, tonsils, and lymph nodes.

The COVID-19 pandemic has prompted many researchers to start eyeing up the ECS in the context of a new therapeutic approach to the disease. So far, research suggests that CB2 activation could produce an anti-inflammatory and immunosuppressive effect[7] that could potentially help to tame an overly aggressive immune response.

ECS-mediated immunosuppression includes several key processes that researchers think are relevant to COVID-19[8]. These include cytokine suppression, inhibition of immune cell proliferation, antibody production, and control over the development of viral disease.

The Role of the Endocannabinoid System in Immunity

Does Cannabis Hold the Key to Future Coronavirus Therapeutics?

If you imagine the ECS as a lock, then cannabinoids are the biochemical keys. They enable us to tweak this system in our favour in certain circumstances. However, the research regarding cannabinoids and coronavirus remains extremely early, and most claims are merely speculation at this point.

Using cannabis in the context of COVID-19 probably won’t involve sitting around and puffing on all of the weed you can get your hands on. Although this would deliver cannabinoids directly to the intended site, chronic use of cannabis in this way could result in worse clinical outcomes[9] due to its effects on the respiratory system.

However, many approved cannabis-based medicines don’t use this method of administration. If any are developed specifically for COVID-19 in the future, they’ll likely come in the form of sprays, capsules, and possibly intravenous preparations. With that said, some medications are inhaled specifically to treat lung infections[10]. Could cannabis join the ranks of these vaporized therapeutics?

Cannabis and Coronavirus: Inspecting the Research

So, we know that the ECS plays an important role in managing the immune response. We also know that molecules from cannabis can help to modulate the ECS. But what does the current research say regarding cannabis and coronavirus? What about CBD and coronavirus? The virus only appeared recently, so it makes sense that we don’t have much data to hand. But a few early studies have yielded some important findings, and ongoing research hopes to continue this trend.

Research published in the journal Preprints examined the effect of CBD on ACE2 receptors. Because the virus relies on these sites to gain entry into host cells, reducing their expression might help to reduce susceptibility to the pathogen. Researchers tested high-CBD cannabis extracts on artificial 3D human models of airways and found the formula to favourably alter ACE2 expression[11]. The team admits that further large-scale investigations are required.

Additional research, published in the journal Cannabis and Cannabinoid Research, looked at the effects of CBD on the cytokine[12] storm that causes ARDS. The scientists created a model of the condition in mice and then administered the cannabinoid. They then measured the levels of inflammation and lung damage, and compared this to mice that received no treatment.

The researchers concluded that “CBD may reduce cytokine storm” and mitigate the effects of an exaggerated immune response. Again, the team stated that more research is required to validate these findings.

Cannabis and Coronavirus: Inspecting the Research

What About Terpenes?

While cannabinoids receive the bulk of attention, there are also over 200 terpenes in cannabis. These aromatic chemicals offer unique effects in isolation, but also synergise with cannabinoids[13]. A research team in Israel tested a blend of terpenes and CBD in human lung cells against a human coronavirus that doesn’t require a level 4 biosafety facility to study.

They tested the terpene blend and CBD in isolation, but found a more protective effect when they administered them together. They also commented on the best way to use this phytochemical blend, writing, “As the lungs are the organs most affected by COVID-19, preventative treatment directly to the lungs, possibly via inhalation, would be the ideal administration route for this potential therapeutic”.

Cannabis and Coronavirus: Don’t Get Your Hopes Up Just Yet

These early findings are interesting to say the least. Cannabis has shown potential in a wide range of health conditions, and it could play a role in the future of the COVID-19 pandemic. However, we can’t draw any conclusions from this early data. Cell studies only paint a very blurry picture of how the same treatments could work in humans. But these findings certainly follow a consistent trend: the endocannabinoid system and cannabis are making a serious mark in the world of medicine.

External Resources:
  1. Treatments for COVID-19 - Harvard Health
  2. The COVID lab-leak hypothesis: what scientists do and don’t know
  3. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 | Acta Pharmacologica Sinica
  4. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis
  5. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines
  6. In quest of a new therapeutic approach in COVID-19: the endocannabinoid system
  7. Cannabinoids and COVID-19 - FullText - Medical Cannabis and Cannabinoids 2020, Vol. 3, No. 2 - Karger Publishers
  8. Cannabis for COVID-19: can cannabinoids quell the cytokine storm?
  9. Multiple clinical risks for cannabis users during the COVID-19 pandemic | Addiction Science & Clinical Practice | Full Text
  10. Inhaled antibiotics to treat lung infection
  11. In Search of Preventative Strategies: Novel Anti-Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues[v1] | Preprints
  12. Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA
  13. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects
This content is for educational purposes only. The information provided is derived from research gathered from external sources.

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