Broad spec CBD reduces viral replication via stress, no result for synthetics

After two years, everyone has grown tired – dare we say we’re stressed. But new research does not recommend we sit back and smoke a joint, or even consume cannabis just yet. Fortunately, though, cannabis formulations consumed orally did reduce coronavirus replication in a lab. Cannabidiol (CBD) regulates the stress response which reduces viral replication according to research conducted on human cells. Not without a catch, though, since the cannabinoid does not reduce coronavirus replication on its own.

Coronaviridae, the family that Sars-Cov2 belongs to, is enveloped in a protective shell and comprised of 29 different proteins. When the virus enters the receptor its proteins need to be broken down (cleaved) so they can bind to human cells.

Blocking viridae and proteins

A study released in early 2022 suggested that large doses of cannabinoid acids, CBGa and CBDa can block Sars-Cov2 from entering the ACE2 receptor. Unfortunately, though, it was not determined how CBDa and CBGa facilitated inhibitory action against the virus. (1) A drug that blocks certain proteins is, however, already used to treat Covid-19.

Quercetin, a flavonoid and cannabis ingredient was shown to block viral entry in vitro at the beginning of 2020. Following an inconclusive clinical trial, a synthetic drug was created by Pfizer a year later that copies quercetin’s mechanism of action with better bioavailability. Essentially, quercetin stops pieces of viridae from binding to the cell. To prevent this binding, quercetin inhibits proteases that cleave the virus’s protein envelope. Cayman Chemical, who produces lipids for the Covid vaccines as well synthetic cannabinoids, released an article last year promoting quercetin for this reason.

Regulating stress and viral replication

Another problem is that the virus doesn’t just enter through the ACE2 receptor. Sars-Cov2 sneaks its way into human cells and causes a lot of vascular damage while incredibly relieving pain through a second site known as neuropilin-1. This second receptor site was despairingly discovered and mostly ignored after several approved vaccines were already halfway through Clinical Trials. That means CBGa and CBDa might not prevent viral infection outside of a test tube and in human patients. More research needs to be conducted, but hope isn’t lost for broad-spectrum and specifically hemp or cannabis-derived CBD.

Released at the beginning of 2022, a study found CBD inhibits viral replication once the virus has already entered the cell. (2) CBD regulates a certain type of cellular stress that prevents proteins from folding into existence, but that stress also facilitates viral replication. By regulating stress on a highway for cells known as the (big breath) Endoplasmic Reticulum, which is as complex as its ghostbuster name suggests, CBD can prevent the progression of Covid-19 infection.

More importantly, specific genes regulated by CBD help the coronavirus replicate. The study noted strong negative associations between CBD’s moderation of one particular gene and Covid-19. While no solid answers have been determined in humans without inconclusive variables, the research was a promising soft start.

Innate immune response

White blood, specifically CD4 T cells are a necessary part of the immune system when going up against a Covid-19 infection. This is the main role of Covid vaccines. THC partially suppresses immune cells function, although the intoxicating cannabinoid is mostly neutral at T cells.

Thankfully, with the cannabis plant being so prone to balance, CBD instead stimulates T cells as well as interferons that promote a natural immune response against viral infection. CBD was earlier shown to inhibit inflammatory cytokine agents as well.

Surprisingly, the T cells induced by Covid-19 infection but also the vaccines counterintuitively help the body cleave the virus which makes it more infectious. A trick performed by the virus; it uses our bodies offensive immune system to unlock its replication machinery. This is only one reason that standard immunizations were destined to fail from the start. (3-5)

I’d like my CBD to be served broad-spectrum from hemp, not yeast

Congeners were included in the University of Chicago’s research without avail. That is, CBD produced via fermentation of genetically modified yeast did not produce a positive result. Hemp-derived CBD testing at 97% pure did, however, provide the promising results reiterated herein. No surprise should be given to a synthetic isolate lacking efficiency against Covid-19, though. This is because an earlier clinical trial co-authored by Raphael Mechoulam on pure CBD did not find a reduction in viral replication. (8)

It seems that even the plant’s broad spectrum is needed considering CBD, like many of its talents, cannot block Covid-19 on its own. Terpenes or flavonoids might be a key to effect but more research is needed to provide further answers; a disappointingly repetitious truth two years later.

With some promise, full-spectrum CBD will begin a phase 2 clinical trial against Long Covid.

Sources

1. van Breemen, R. B., Muchiri, R. N., Bates, T. A., Weinstein, J. B., Leier, H. C., Farley, S., & Tafesse, F. G. (2022). Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants. Journal of natural products, 10.1021/acs.jnatprod.1c00946. Advance online publication.
2. Nguyen, L. C., Yang, D., Nicolaescu, V., Best, T. J., Gula, H., Saxena, D., Gabbard, J. D., Chen, S. N., Ohtsuki, T., Friesen, J. B., Drayman, N., Mohamed, A., Dann, C., Silva, D., Robinson-Mailman, L., Valdespino, A., Stock, L., Suárez, E., Jones, K. A., Azizi, S. A., … Rosner, M. R. (2022). Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses. Science advances, eabi6110. Advance online publication.
3. Kalfaoglu, B., Almeida-Santos, J., Tye, C. A., Satou, Y., & Ono, M. (2020). T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis. Frontiers in immunology, 11, 589380. https://doi.org/10.3389/fimmu.2020.589380
4. Silva-Cayetano, A., Foster, W. S., Innocentin, S., Belij-Rammerstorfer, S., Spencer, A. J., Burton, O. T., Fra-Bidó, S., Le Lee, J., Thakur, N., Conceicao, C., Wright, D., Barrett, J., Evans-Bailey, N., Noble, C., Bailey, D., Liston, A., Gilbert, S. C., Lambe, T., & Linterman, M. A. (2021). A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice. Med (New York, N.Y.), 2(3), 243–262.e8. https://doi.org/10.1016/j.medj.2020.12.006
5. Gupta, S., Su, H., & Agrawal, S. (2021). Immune Response to SARS-CoV-2 Vaccine in 2 Men. International archives of allergy and immunology, 1–10. Advance online publication. https://doi.org/10.1159/000520046
6. Crippa, J., Pacheco, J. C., Zuardi, A. W., Guimarães, F. S., Campos, A. C., Osório, F. L., Loureiro, S. R., Dos Santos, R. G., Souza, J., Ushirohira, J. M., Ferreira, R. R., Mancini Costa, K. C., Scomparin, D. S., Scarante, F. F., Pires-Dos-Santos, I., Mechoulam, R., Kapczinski, F., Fonseca, B., Esposito, D., Passos, A., … Hallak, J. (2021). Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Cannabis and cannabinoid research, 10.1089/can.2021.0093. Advance online publication.