Should we be worried?

[shredder]

Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model

The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F[1] mice. Animals were gavaged with either 0, 246, 738, or 2460 mg/kg of CBD (acute toxicity, 24 h) or with daily doses of 0, 61.5, 184.5, or 615 mg/kg ...

www.ncbi.nlm.nih.gov

 

[Summer]

All I can tell you is the amount of CBD needs to be on label. I wouldn't give CBD to my pets.

 

[shredder]

All I can tell you is the amount if CBD needs to be on label. I won't give CBD to my pets.

I accidentally stumbled onto this site and was quite surprised.

I was googling about liver enzymes that break down cannabis oil, and got sidetracked.

 

[florduh]

I've seen this study before and it did cause me some concern. I consume a decent amount of hemp CBD and CBG. I also had severe liver damage due to a bad reaction to acetaminophen. That's actually why I got into cannabis in my late 20's. I had unbearable pain and was unable to take any pain relievers due to the liver damage.

I'm pretty sure this is a "dose makes the poison" situation. Yes, the scientists claim they're using equivalent mouse doses to what humans would take. But that's not an exact science. Even their "maximum recommended dose" for Epidiolex in humans sounds high. 20mg/kg would be like a gram and a half of pure CBD per day.

I keep an eye on my bloodwork. Never have elevated liver enzymes despite high CBD intake. Important to remember that lab mice aren't humans. If they were nobody would get cancer or age since we've managed to more or less cure both conditions in mice.

 

[UneOnceDeLumière]

I'm pretty sure this is a "dose makes the poison" situation. Yes, the scientists claim they're using equivalent mouse doses to what humans would take. But that's not an exact science.

They have forced a "shock liver" (ischemic hepatitis).

And yes, They only did a basic weight equivalent. which differs, specificaly for liver, As we don't had the same diet through the evolution. Exemple, Carnivorous assimilate protein efficiently, we don't. Mice enzymatic metabolism will be different than a basic linear weight correlation. Why that study can't be used as reverted posology.

Here, it is what an acute hepatotoxicity test gives at some ammount, for any drugs. poor little pinky and the brain..

Even their "maximum recommended dose" for Epidiolex in humans sounds high. 20mg/kg

Yes, it is high...
Sativex, in Europe, for sclerosis mostly in france, limit the posology to 30mg THC/CBD a day, diluated through the day. (30/62= 0.48mg/kg ! a day. I took the world average. not the American one, susceptiblity with their IMC .. )

To get back to the study.
They've shown a shocked liver starting at 615mg/kg (high billirubin, with limited ALT/AST). But Not in every mice.
I'm not talking about the 2000mg gavage.. and the lethargy.. low bloodstream.. ischemia.

However The 61mg/kg show better results than usual (lower GGT). While 184mg/kg already show a liver over-activity.(bilirubin increased, but normal ALT/AST)

The enzymatic activity is known, giving interaction with other drugs (hemorrhage with anti-coagulent, or statin canceling).

1:1 ratio thc:cbd being the most promising for medical use. And 100mg THC being already a good ammount. I would stay in that range for CBD posology.
And so, 3mg/kg (2×100mg) a day being already an high ammount. 6 times the sativex day limit posology.. still far from epidiolex 20mg/kg.. then there is no posology for epileptic crisis here.
Even if those mice had better liver results at 61mg/kg (enzymatic enhance?). We can't make a linear correlation.

Then i size my 000 caps afterward, my highness being the scale...

 

[UneOnceDeLumière]

To those who want, and/or can go further.

Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants - PubMed

The seven CYP clusters are greatly expanded in the mouse with 72 functional genes versus only 27 in the human, while many pseudogenes are present; presumably this phenomenon will be seen in many other gene superfamily clusters. Complete identification of all pseudogene sequences is likely to be...

pubmed.ncbi.nlm.nih.gov

72 genes for mice vs 27 for human (cytochromes p450)
Which may provide an over (or under?,) reactivity, to CBD here..

And that's only for the liver assimilation-reaction part.

Cannabinoides being neuro-active. The whole neurostructure is also to be taken into consideration.
Mice being easily prompt to "over-dose" at basic weight equivalence. Increased lethargy, bringing faster ischemia.

CBD playing with serotonin, which is the main difference between mice and human neurostructure..

Neuroscience: Comparing the brains of humans and mice | Nature | Nature Portfolio

Neuroscience: Comparing the brains of humans and mice

www.natureasia.com

Difference which makes that other study below, unrelevant.. rodent use for 5-HT..

Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain

Low dose of cannabidiol ameliorates mechanical allodynia and anxious behavior and restores impaired serotonergic transmission in a neuropathic pain model in rats.Clinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis ...

www.ncbi.nlm.nih.gov

And there is also an astrocytes difference, bringing different response to oxidative stress between mice and humans.

Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes - Nature Communications

Astrocytes are important players in brain development, homeostasis, and disease. Here, the authors compare the transcriptional profiles of human and mouse astrocytes. They report species-specific susceptibility to oxidative stress and response to hypoxic and inflammatory conditions.

www.nature.com

Anyway, don't eat 1kg300gr (35 onces ..!) of 10% CBD strain.. (2000mg/kg..)

And Inhaling cannabinoides have shown way less drugs interactions than edibles. ingested CBD giving the most interaction, while THC inhalation has shown quite none.. for now.

 

[VegNVape]

I think we should definitely be worried - worried they are conducting these tests on animals.
"The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice"
Fuckin barbarians.

 

[C No Ego]

I think we should definitely be worried - worried they are conducting these tests on animals.
"The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice"
Fuckin barbarians.

what about all the mice that have gotten into the pot stash and ate a whole lot of it gluttonous like !!?

 

[VegNVape]

what about all the mice that have gotten into the pot stash and ate a whole lot of it gluttonous like !!?

What about them? What are you even talking about?
I understand you are having a laugh but it's not really a funny subject. I guess it's easy to make jokes when it's not your own neck on the line, or your own species.

Sorry, but I really don't see any comedy value in animal testing.

 

[UneOnceDeLumière]

We've history data of pet falling into pot stash unfortunately..
And Kids getting intoxicated too, with un-decarbed flowers ingestion..

Easy edibles must stay away from them.

Yet, in france, as CBD is legal, some monkeys gavage themselves, getting scammed as being a "miracle" product..
All sold by switzerland..
Their datas gonna be more relevant...


"Rien qu'en me levant,
Je couches les ignorants."

 

[checkyourlibido]

I think we should definitely be worried - worried they are conducting these tests on animals.
"The goal of this study was to investigate Cannabidiol (CBD) hepatotoxicity in 8-week-old male B6C3F1 mice"
Fuckin barbarians.

It's amazing how easily they can manipulate the mouse genome. Just by adding or removing a gene, they can understand what it does in the body. Mice are powerful tool for modelling specific diseases especially with mutations. That's just one of many benefits to using mice.

Hopefully one day we won't have to use any live creatures for any testing.

 

[VegNVape]

It's amazing how easily they can manipulate the mouse genome . . . . . . . Hopefully one day we won't have to use any live creatures for any testing

That's the thing - we don't actually have to, it is our choice to do so. But is not the choice of the sentient beings on which we conduct these experiments.

I am not going to get into this one any further as it is not what the thread is about, plus, it's probably not really a topic for FC - but I do have to call it out when I see it.

 

[UneOnceDeLumière]

Mice are powerful tool for modelling specific diseases especially with mutations.

Not that much..
"Gene manipulation" is mostly/only about gene "choice". And As long as you deviate too much from the original, it died, or never get born.
They may make some become yellow, by killing their liver...
But we will never see a yellow one with electric sparks pika, pika..!

Genetically manipulated mice: a powerful tool with unsuspected caveats

Although genetic manipulations in mice have provided a powerful tool for investigating gene function in vivo, recent studies have uncovered a number of developmental phenomena that complicate the attribution of phenotype to the specific genetic change. ...

www.ncbi.nlm.nih.gov

And about disease, it's the pig which has the most similarities with human. We share the same immuno system, and so exogenous disease. Why some religion forbid it, as politcal tool, to keep an healthier growth of population..
But here, i diverge from fucking "combustion"..

Hopefully one day we won't have to use any live creatures for any testing.

That's a wrong utopy. Any compound used, manufacturerd, synthetised, or natural from mother the whore earth, had to be "tested" the first time.
If it's not by "guinea-pig", they are called the "pioneer".
U don't even know how many pinky are in FC.. me, i may have an idea of what i want to do tonight..

 

[GoldenBud]

if the liver will have to convert some big amount of CBD to 7-Hydroxy-CBD and/or THCD9 to 11-Hydroxy-THC in short time I don't think it will accepted for long time. I think even ALT/AST/GPT indications in a blood test should be higher since how the liver have to be worked....
but with moderate amount of CBD/THC? I don't see much a problem, do your blood test every year and that's it....