Covid-19 causes inflammation by hacking endocannabinoid synthesis

Cannabinoids are fat. Those particular molecules known as cannabinoids are all fatty acids, whether they exist within the cannabis plant or us. Other essential and non-essential fats have differing effects on the endocannabinoid system (ECS), as well. Interestingly, different fats and endocannabinoid metabolites are affected by Covid-19, which may act as a unique fingerprint for disease severity and inflammation.

A lot of discussions erupted over cannabis as a treatment for Covid-19. (1) Internally, endocannabinoid function is uniquely disrupted by Covid-19, potentially leading to widespread symptoms such as heart inflammation or cancer progression. But, the treatment might not be CBD by itself. The ECS functions as the prime target of critical cannabis molecules while also keeping us alive, so its tone is vital. (2)

What the heck is an eicosanoid?

Two endocannabinoids (2-AG, anandamide) break down and produce the pro-inflammatory arachidonic acid (AA). These are signalling molecules with a host of important functions that respond to cannabis components, among other things. Endocannabinoids are part of a group called eicosanoids, which includes a handful of other signalling molecules produced once AA breaks down.

Unfortunately, a stale tradition follows the literature by overlooking the defective synthesis of crucial endocannabinoids as a mechanism of Covid-19. Research far too often focuses on the common metabolite, arachidonic acid (AA). (3, 4) Thankfully, the whole endocannabinoid system has not been completely forgotten over the past 18 months.

Where else does arachidonic acid come from?

Arachidonic acid (AA) is also a breakdown product of different phospholipids (fats), such as linoleic acid. However, a report on the vaccine, which contains phospholipids that have both positive and negatives consequences, will have to wait. More importantly, those fats also provide crucial protection for cells.

Some research suggests linoleic and arachidonic acid supplements can stop other coronaviruses from replicating and entering cells. (6) Furthermore, a more recent study found that Sars-Cov2 uses a linoleic acid-binding pocket to attach to receptors. (7) So, it is no surprise to find ongoing and critical research detailing endocannabinoid metabolites as therapeutic targets for Covid-19.

But there is a problem. Sars-Cov2 induces arachidonic acid and is the first step in the production of deadly cytokines. So, AA supplements are certainly problematic — without mediation.

How are endocannabinoids made?

The enzymes PLA2 and PLD quite literally convert lipids (phospholipids) into arachidonic acid (AA). (9) Novel lipids used in mRNA vaccines uniquely transform and metabolize, but they are still phospholipids — Which might prove to be problematic. That is because misguided metabolism of lipids and AA can cause heart inflammation, as well as a mechanism that causes blood to clot, PAF (platelet-activating factor.)

Additionally, the lipids in the vaccines are bound to a blood clot-inducing (PAF) precursor known as phosphocholine.

Active Covid infections disturb the synthesis and function of AA. Meaning, Covid-19 may disrupt endocannabinoid synthesis, leading to a depletion of anandamide and PEA. These two anti-inflammatory agents provide balance in the axis. If endocannabinoid dysregulation holds up to experimentation, then a key treatment could lay in enzymes that break down fatty acids and synthesize cannabinoids.

Fatty acids supplements or cannabinoid therapy?

Linoleic acid can lock the virus in a non-infectious position inside the receptor. (7) Fatty-acid supplements might add fuel to the inflammatory response in an upset lipid axis, though. Therefore, specific enzymes involved in steering pro-inflammatory lipids and eicosanoids may reveal better treatment.

Other studies assume that the reduction of AA is beneficial. So, a deeper story must be at foot. Enzymes that help degrade lipids into endocannabinoid metabolites are far from monotone. Arachidonic acid can degrade into both pro and anti-inflammatory agents. Indeed, a complex song of the endocannabinoids.

Long Covid, inflammation and endocannabinoid degradation

New evidence detailed in a preprint, a study published before review, suggested that spike proteins lodged in abnormal CD cells may cause Long Covid symptoms. (9) One type of cell that can hold coronavirus proteins (CD16) for over a year is known to release arachidonic acid, but this depends on the enzyme known as PLC. So, protecting the endocannabinoid system is critical after a Covid infection.

Covid-19 induced clinical endocannabinoid and PPAR deficiency proposed

A host of issues will occur if the fatty acid axis (lipidome) is thrown out of order by the disease. Endocannabinoid production appears to be partially disengaged by Covid-19, which can allow high levels of inflammation. Dysregulation within transient endocannabinoid responses will cause a complete vicious cycle in fatty acids stores. (10)

PEA, a derivative of anandamide, has been researched for its use against influenza and the common cold. The kicker has been a connection this author noted in January and February — 2020.

The cytokine interleukin-6 is known as a lethal inflammatory agent in Covid-19. However, an anandamide derivative known as PEA can regulate interleukin-6. PEA and EETs especially settle cytokines due to the activation of PPARs, a special set of messengers. Many biological mechanisms maintain balance, such as PPARs, especially the lipidome. For many reasons, inflammation will occur if endocannabinoid synthesis is disrupted — with or without Covid-19.

More research is needed to determine what blend of cannabinoids, terpenes, and foods will best promote endocannabinoid health. A better understanding of endocannabinoid production and metabolism can prevent the lethal potential of Covid-19. Orchestration of the eicosanoid storm might be a key, even if the Saliva Study from Stanford proves the vaccine does not prevent infection (transmission) and only prevents symptoms and death.

Let us know in the comments if you want to learn how Covid-induced inflammation and endocannabinoid degradation is connected to cancer. And, can the vaccine also cause inflammation with causal links to cancer promotion and is there a role for the ECS?

Show your work

• A covid-19 induced eicosanoid storm can be pushed into a vicious cycle and hyper-progression.
• Cox-1 inhibitors can reduce blood events but cause gastrointestinal issues.
• CBD targets Cox-2 and can aid in inflammation but does not target Cox-1. This puts CBD at the helm of causing thrombosis. Conversely, however, CBD is a known blood thinner and should reduce this risk.
• Cox-2 inhibitors will reduce headaches. However, there is a chance blood clots will be exasperated!
• CBDa is a potent Cox-2 inhibitor but also inhibits Cox-1. Therefore, it is a balanced anti-inflammatory agent with a massive peripheral 5HT1a reuptake to reduce gastrointestinal distress.
• CBD is a potent inhibitor of the CYP2C subset, a site of critical drug interactions. This targets AA degradation in EETs, specifically.
• CBD should knock down EETs which should knock PPARs and worsen symptoms.
• Conversely, CBG > CBD will help agonise PPARs through other mechanisms.
• PEA acts as a common cold regulator via PPARs – major regulators of the lipidome.

Sources

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2. ECS homeostasis
3. Ripon MAR, Bhowmik DR, Amin MT, Hossain MS. Role of arachidonic cascade in COVID-19 infection: A review. Prostaglandins & Other Lipid Mediators. 2021 Jun;154:106539. DOI: 10.1016/j.prostaglandins.2021.106539.
4. Shoieb, S.M., El-Ghiaty, M.A. & El-Kadi, A.O.S. Targeting arachidonic acid–related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles. emergent mater. 4, 265–277 (2021). https://doi.org/10.1007/s42247-020-00136-8
5. Ripon, M., Bhowmik, D. R., Amin, M. T., & Hossain, M. S. (2021). Role of arachidonic cascade in COVID-19 infection: A review. Prostaglandins & other lipid mediators, 154, 106539. https://doi.org/10.1016/j.prostaglandins.2021.106539
6. Vivar-Sierra, A., Araiza-Macías, M. J., Hernández-Contreras, J. P., Vergara-Castañeda, A., Ramírez-Vélez, G., Pinto-Almazán, R., Salazar, J. R., & Loza-Mejía, M. A. (2021). In Silico Study of Polyunsaturated Fatty Acids as Potential SARS-CoV-2 Spike Protein Closed Conformation Stabilizers: Epidemiological and Computational Approaches. Molecules (Basel, Switzerland), 26(3), 711. https://doi.org/10.3390/molecules26030711
7. Toelzer, C., Gupta, K., Yadav, S., Borucu, U., Davidson, A. D., Kavanagh Williamson, M., Shoemark, D. K., Garzoni, F., Staufer, O., Milligan, R., Capin, J., Mulholland, A. J., Spatz, J., Fitzgerald, D., Berger, I., & Schaffitzel, C. (2020). Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein. Science (New York, N.Y.), 370(6517), 725–730. https://doi.org/10.1126/science.abd3255
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