Mice Are Not Humans

[Makrosky]

I don't know if you are aware of what happened lately in France with a Phase 1 clinical trial of a compound (BIA 10-2474) which inhibits the enzyme responsible of degradation of some endogenous cannabinoids.

1 healthy individual died and 4 other healthy ones are in comma.

(http://www.sciencemag.org/news/2016/01/more-details-emerge-fateful-french-drug-trial)

I haven't found info on which animals did they choose for the pre-clinical phase (before Phase 1) but most probably it was mice. Considering the Phase 1 usually starts with a very reduced ammount for safety and intraspecies differences you can see how big the differences can be from mice to humans.

The final explanation of what happened hasn't been released yet. We'll see....

 

[Koveras]

A valid point, and although I'm sure this argument has been had many times

1) Animal research is still useful

2) Caution is always warranted

Hence why if something proves to be safe in Mice, as above, we should still be extremely cautious.

...and why when something shows there may be negative health effects in mice (like my citrate example Citrate Impairs Glucose Tolerance And Promotes Inflammation | Ray Peat Forum) we should be cautious. Especially when the downsides to caution are minimal or non-existent (as in choosing dairy or eggshell calcium over calcium citrate, or food over magnesium citrate).

I suppose if you wish to summarily dismiss all animal research, that is your prerogative. I will keep sharing it though, because I believe it says something of value even if the picture is incomplete.

 

[Makrosky]

Dismissing animal research would be stupid. That was not my intention. I just wanted to emphasize some caution when stating conclusions based ONLY on animal research. Or to put it in other words : provide some more context on animal studies.

Please keep sharing what you find relevant. Discussion and wider context benefits us all.

 

[Koveras]

That's fair, appreciated

 

[Such_Saturation]

Anandamide is PUFA derivate. Big shock guys!

Mice Are Not Humans

More surprises!

 

[Wilfrid]

When it comes to rodent based medical studies, I always found the following quote of Robert Burns very insightful:

" Most in vivo basic research is performed on rodents with the hope that some of it will have a positive impact on human health. Some treatments effective in the mouse model have proven to be ineffective in man. Conversely, those found to be ineffective in mice never get the opportunity to be tested in man.

Man is a diurnally active-nocturnally resting animal. Mice and rats are exactly the opposite, i.e., nocturnally active-diurnally resting. Research commonly is performed by diurnally active humans working during the diurnal phase on rodents. This, however, is when the research subjects are in their resting phase, being nocturnally active animals. In a general sense, it is not logical to expect data obtained from resting animals to be transferable to active humans. A more logical transfer from mouse to man would be expected if the research was carried out during the rodent's active period (nocturnal phase): active to active (even resting to resting) transfers are more scientifically valid than resting to active or active to resting transfers. One way to avoid the common pitfall of obtaining data from resting animals (diurnal phase) is to perform the research during the rodent's nocturnal (active) phase. This means working at night or with the animals synchronized (takes 10–14 days) to a reversed 12:12 light:dark cycle so that their nocturnal (active) period coincides with the diurnal period for the researcher. When this is done, one should work in low red light, which is not visible to rodents.

The following scenario indicates some of the problems associated with working on resting animals during their diurnal phase and transferring the data to the diurnally active human. The scenario presented is a general one, but it has its origin in the well-documented field of chronotoxicology/chronopharmacology (Reinberg, 1992). A chemical food additive is tested in a mouse model for carcinogenicity. The test is done when the susceptible biochemical event (e.g., rate of DNA synthesis) happens to be at its lowest (trough) activity, i.e., 1200 (mid-diurnal or resting phase). No cancers are produced. The data are accurate: exposure to the chemical at 1200 did not result in any cancers. The data are used to classify the chemical as non-carcinogenic and it is approved for use as food additive. However, if the same dosage of the same chemical had been tested at 2400 (mid-nocturnal or active phase), a time of maximal susceptibility of the biochemical event involved, 40% of the animals would have developed liver cancer and the compound would be classified as carcinogenic and unsafe. For human safety it becomes extremely important to test for carcinogenicity/toxicity of a compound when the mouse is at its most biochemically susceptible time (could be mid-night, a time of maximal DNA synthesis) to that compound, not when the mouse is at its most resistant time (could be noon, a time of minimal DNA synthesis). Only in this way would the carcinogenic/toxic potential of the compound be discovered. To test a food additive ( or any chemicals / drugs for that matter ), which in reality is highly carcinogenic/toxic, during a specific point in the host's circadian system when the true carcinogenic/toxic potential of the compound is “hidden” by biological time is inappropriate, misleading, and dangerous.»

It could have been interesting to know how the in-vivo research on animals was first made.

 

[Hugh Johnson]

Even human research is limited. Niacinamide is great, but for some individuals it causes trouble. You always have to pay attention.

 

[Drareg]

I don't see where it talks about the mice in this article? It imply a lower dose of this med was OK in a previous study of humans?
They upped the dose and probably messed that up, dosing methylene blue situation perhaps?
Be interesting to see what comes out.

Is this based off research from pregnenolone blocking THC in higher doses, this implied pregnenolone to be the great vibes people get from weed?
Scumbags if it is,it's just perfectly normal to find a natural substance to have amazing healing qualities and think, let's add a random molecule and patent it.
It's like a sport, if someone dies you still get a pat on the back for trying and playing the game, if nobody dies and just has side effects like a **** falling off your a success.