Nerfing the Abstract #4
The Slow Nerf
Cannabinoids and COVID is Horse paste on steroids.
3rd Rail.
Taboo.
Everything wrong with society can be summed in up in irrational Cannabinoid policy.
A recent Women’s Basketball player (Griner) was snagged in Russia for her vape pen and is being offered US presidential prisoner swaps for Iranian arms dealers while thousands of Americans are still imprisoned for cannabis possession in States that are currently cannabis legal. Tulsi Gabbard, once again, mops the floor with Kamala Harris over this insanity.
It is a world of hyper charged hypocrisy and political platitudes.
Sadly, the science in the field often reflects this religion.
This is not an overt Abstract Nerf. You have to know the people, who they work for and what work they have published in the past to see it. It is a slow Nerf. One you recognize as the authors show their cards over time.
The paper makes the case that cannabinoid use (now deemed a pandemic essential business in the US) is up and maybe we need to be careful about this given all the C19 drugs. Nothing wrong here. Cannabinoids are like grapefruit juice in that they slow CYP3A, CYP2C9, and CYP2C19 and this can slow the metabolism of drugs that rely on these enzymes like warfarin and clobazam etc.
What is not obvious to the reader is that the authors have funding from Zynerba which is a transdermal cannabinoid company that likes to highlight these gastric/hepatic-portal issues with cannabinoids as transdermal applications are mostly free of them.
To understand this story you have to catch up on this History which has created a ping pong match of papers refuting each other. Zynerba authors claim CBD can turn into THC in gastric ‘simulations’. It is true that people can convert CBD into delta8 THC with a Lewis acid in vitro but evidence of this happening in the human gut must be confirmed with detection of THC in the blood and this never seems to pan out despite the wishes of companies selling transdermal patches that don’t suffer from gastric routes of administration.
Now, these same Zynerba authors are at it again but the C19 audience now has honed bullshit detectors to see through these things.
First critique of the opinion piece. Why is there no mentioned of Ivermectin in the article? It is one of the most commonly used C19 drugs and it utilizes the same liver enzymes as the cannabinoids (CYP3A4 and CYP2C19).
It might be that IVM has been heavily studied and the p450 concerns initially raised have proven to not be a concern as the metabolism of the drug doesn’t create and toxic metabolites and the drug has been dosed over a billion times in the population. This is also true of cannabinoids, in that they have thousands of years of human dosages and may even have more human dose hours than IVM.
Nevertheless some concerns with cannabinoids were found in the Epilepsy field with Valproic acid and clobazam. These are toxic drugs that require the same p450 enzymes for clearance and cannabinoids get blamed for their shortcomings.
This is the slow Nerf. An uninformed reader on this topic might relate cannabinoids with hepatocellular injury when its really the Valproic acid that does that and the cannabinoids competing for the same liver enzymes makes it a lot more obvious. The cannabinoids themselves have proven to hepatoprotective.
Or, one might balance the perspective by highlighting the interesting work looking at THC and its impact on SEB toxicity.
https://www.frontiersin.org/articles/10.3389/fphar.2020.00893/full
https://pubmed.ncbi.nlm.nih.gov/32754917/
SEB sequences exist in the Spike protein in the Vax and SARs-CoV-2 and have been documented in MIS-C.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082696/
https://www.pnas.org/doi/10.1073/pnas.2010722117
There is no mention of any of the potential upside of cannabinoids in C19 therapy. Just the fear porn that transdermal might alleviate.
Not even the most obvious Acetominophen replacements come to the forefront.
Tylenol is commonly recommended for fevers and it is a cannabinoid mimetic. A very shitty one that has a toxic liver byproduct known as NAPQ1. NAPQ1 creates glutathione deficiency which is a serious issue for C19 patients.
https://pubmed.ncbi.nlm.nih.gov/32463221/
Phytocannabinoids dont do this. Despite this, one should question if fever reduction is the right plan for COViD, but other aspects of COX-2 inhibition and prostaglandin biology may be better addressed with cannabinoid mimetics that don’t generate toxic liver byproducts.
This is the slow Nerf. Your company makes transdermals which evade the hepatic-portal system, so it becomes your job to cheer lead for these routes of administration.
If it were a balanced article, you might highlight some of the promise cannabinoids have shown in C19 treatment. This requires high dosages which are unlikely to be obtained with transdermals.
But “Letters to the Editor” are summed up quite nicely in memes.
And to the Authors credit, their relationships with Zynerba are clearly disclosed.
The process of science is often competing financial interests angling. As long as there is disclosure that’s the best we can hope for. There is nothing wrong with that in a marker free of manipulation, politics and censorship.
The dude abides.