CBD reduces plaque, improves cognition in mouse model of Alzheimer’s(jagwire.augusta.edu)
jagwire.augusta.edu
CBD reduces plaque, improves cognition in mouse model of Alzheimer’s
https://jagwire.augusta.edu/cbd-reduces-plaque-improves-cognition-in-model-of-familial-alzheimers/
42 comments
Don't they selecte mice that got alz naturally?
There are transgenic mice where they have spliced genes to cause disease, but to me this is not a probable way to learn how to cure Alzheimer's.
The reason is, there are very limited choices in which mouse line to use. You basically have to pick from a menu of transgenic mice from some supplier. So you would have to be lucky enough that a supplier breeding transgenic mice just happens to have picked, with an educated lucky guess, a combination of genes that expresses a disease enough like Alzheimer's when spliced into a non-human host that something that has some effect on the mouse disease also has an effect on the human disease, compounded with being lucky enough to find a treatment for the mouse disease at all, compounded with the luck of picking that mouse line from the menu of dozens of mouse lines with human genes spliced in.
So lets say a time traveler from the year 2321 hands you a vial with the cure for Alzheimer's in it, and you want to test if it works. So you open the mouse catalog, and you see a dozen transgenic mice choices. Lets say, by some cosmic coincidence, one of those mouse lines out of the dozen choices, again by luck since it's unlikely that out of a couple of spliced genes they would ever happen upon a mouse line that it would ever work, has the right gene that coincidentally the human cure will also work on that line of mice. By far the most likely outcome (11/12 times) is you order mice, they are acting like they have a brain disease, you inject them with the future cure and it doesn't help them at all. This is when you know for a fact you do have a cure for humans. This is why I'm saying these mouse studies are a waste of money and research effort. If you have a cure for Alzheimer's the mice are very unlikely to show improvement, and things that improve the behavior of the mice are incredibly unlikely to work in humans.
So why do they do it? Well, there is a big pool of money available to study Alzheimer's and there are catalogs with mice in them, and you can inject mice with whatever random thing you want without a lot of 'having a reason it might work'. It's like the guy looking for his keys under a street light. When you ask him if that's where he lost his keys he says "No, I lost them way over there." Ok why not look where the keys might be? "It's too dark to see over there". In this case, it's "we don't know how to do an experiment that might be useful but there is funding and we can order mice".
The reason is, there are very limited choices in which mouse line to use. You basically have to pick from a menu of transgenic mice from some supplier. So you would have to be lucky enough that a supplier breeding transgenic mice just happens to have picked, with an educated lucky guess, a combination of genes that expresses a disease enough like Alzheimer's when spliced into a non-human host that something that has some effect on the mouse disease also has an effect on the human disease, compounded with being lucky enough to find a treatment for the mouse disease at all, compounded with the luck of picking that mouse line from the menu of dozens of mouse lines with human genes spliced in.
So lets say a time traveler from the year 2321 hands you a vial with the cure for Alzheimer's in it, and you want to test if it works. So you open the mouse catalog, and you see a dozen transgenic mice choices. Lets say, by some cosmic coincidence, one of those mouse lines out of the dozen choices, again by luck since it's unlikely that out of a couple of spliced genes they would ever happen upon a mouse line that it would ever work, has the right gene that coincidentally the human cure will also work on that line of mice. By far the most likely outcome (11/12 times) is you order mice, they are acting like they have a brain disease, you inject them with the future cure and it doesn't help them at all. This is when you know for a fact you do have a cure for humans. This is why I'm saying these mouse studies are a waste of money and research effort. If you have a cure for Alzheimer's the mice are very unlikely to show improvement, and things that improve the behavior of the mice are incredibly unlikely to work in humans.
So why do they do it? Well, there is a big pool of money available to study Alzheimer's and there are catalogs with mice in them, and you can inject mice with whatever random thing you want without a lot of 'having a reason it might work'. It's like the guy looking for his keys under a street light. When you ask him if that's where he lost his keys he says "No, I lost them way over there." Ok why not look where the keys might be? "It's too dark to see over there". In this case, it's "we don't know how to do an experiment that might be useful but there is funding and we can order mice".
Mice don't get alz. So they have bred strains of mice that get similar symptoms and try the medications on that.
In a mouse model.
Every disease plaguing humans has been cured 100x in mouse models.
Every disease plaguing humans has been cured 100x in mouse models.
Seems safe enough to test on humans even if it's not effective. Did the paper mention the dosage required? There must be test subjects out in the wild that regularly consume high quantities of CBD.
I consume high quantities of CBD most days. It's actually pretty cheap in the US if you get it in plant form. You can get it online because it's legal to ship hemp (i.e. cannabis without THC). The extracts, pills, oils etc are super super expensive.
I recommend getting CBD cannabis, making edibles or smoking it. I mix it 1:1 with THC weed, and smoke to a point I'm not high. It's been one of the best things that I did for my mental health, up there with getting a cat, going to therapy and getting regular exercise.
I recommend getting CBD cannabis, making edibles or smoking it. I mix it 1:1 with THC weed, and smoke to a point I'm not high. It's been one of the best things that I did for my mental health, up there with getting a cat, going to therapy and getting regular exercise.
It makes a sort of sense to start inexpensively with a species for which so many incurable human diseases are actually turning out to be curable. Even if a cure is found that does not work in humans it helps map the shape of underlying difference between genetically divergent species. If a human body cannot respond to a cure that a mouse body can, the answer to the question of why not could be valuable.
Given the number of things we find that work on mice but not humans, I wonder how many things that would work on humans we haven't followed up on because they did not work on mice?
Maybe. Or we’re studying a search space with ever diminishing returns of success in the approach. We may have exhausted the utility that animal testing gives for lots of things due to divergent evolution meaning that very few, and ever decreasing, remaining therapies that work in animal models are extractable to humans. Maybe we need several orders of magnitude better models of how the human body works and chemistry works mathematically (and I know this is being worked on with lots of approaches being investigated). Then you can simulate drugs and skip several levels of expensive drug development. Any startup or community of startups that crack this nut can likely eat the current medical research community.
Or you can go the unethical and often illegal human testing route which is also a more mixed bag of results than would be ideal.
Or you can go the unethical and often illegal human testing route which is also a more mixed bag of results than would be ideal.
Maybe it wouldn't be so easy to accurately simulate an organism made of trillions of cells, each containing millions to billions of proteins which oscillate, diffuse, and interact with each other millions of times a second.
I don't think we are anywhere close to having exhausted the lessons we are learning from mouse models. They must always be taken with the caveat that mice and humans have significant differences in biology. But if we want to understand how complex organisms work, there isn't much better than an cohort of actual organisms to manipulate and observe in controlled environments. This gives insight and helps us to understand other species, including our own, by analogy.
I don't think we are anywhere close to having exhausted the lessons we are learning from mouse models. They must always be taken with the caveat that mice and humans have significant differences in biology. But if we want to understand how complex organisms work, there isn't much better than an cohort of actual organisms to manipulate and observe in controlled environments. This gives insight and helps us to understand other species, including our own, by analogy.
My grandfather on my moms side smoked weed,ran marathons, kept his faculty position at the University, and took up new hobbies, up until the Alzheimers went to far to do any of that. My grandfather on my dads side lead a similar lifestyle (minus the the weed smoking) and ended up in the same situation.
Studies are always coming out saying that these things are all helpful, but at the end of the day how long do you get to live and can you really beat your genes?
Most weed have low amounts of CBD, so not sure if your anecdotal story would fit here.
It all comes down to the strain. High CBD & Low THC strains [0]
[0]: https://www.leafly.com/news/strains-products/10-best-cbd-can...
[0]: https://www.leafly.com/news/strains-products/10-best-cbd-can...
Ah, I was not aware of this.
Yeah, sadly I couldn't find a way to read the paper beyond the abstract for free, but the doses I've seen for CBD are like ~10 to 100x what you'd generally get from smoking weed I think. Not to mention that it's usually taken orally, not smoked, but again I can't read the paper so for all I know they were massaging it into their scalps.
Sci-hub will have the paper available
I am.
Someone who vaporizes CBD/THC strains (all of them) still still getting way more CBD compounds than someone who isn't using cannabis at all.
Someone who vaporizes CBD/THC strains (all of them) still still getting way more CBD compounds than someone who isn't using cannabis at all.
That's the danger of these stories. Addicted people claim they are doing good to themselves while taking their drug.
Cannabis is not physically addictive and no reasonable LD has ever been found.
The only downside of pot is whatever you’re missing out while couched-in
The only downside of pot is whatever you’re missing out while couched-in
This is factually false, cannabis is addictive and you do experience withdrawal if you stop using it after habitual long term use (anxiety, depression, among other withdrawal symptoms).
I'm not saying this is an argument for making it illegal, caffeine is physically addictive and certainly you experience withdrawal if you stop using it suddenly, etc.
However, saying cannabis is not addictive at all is just propaganda. If any chemical does something measurable in your body, you will almost certainly experience withdrawal symptoms if you suddenly stop using it after long term use. Withdrawal symptoms being unpleasant is basically the definition of physical addiction.
I'm not saying this is an argument for making it illegal, caffeine is physically addictive and certainly you experience withdrawal if you stop using it suddenly, etc.
However, saying cannabis is not addictive at all is just propaganda. If any chemical does something measurable in your body, you will almost certainly experience withdrawal symptoms if you suddenly stop using it after long term use. Withdrawal symptoms being unpleasant is basically the definition of physical addiction.
I think the addictive vs. non-addictive debate is mostly about what people mean by the word "addictive." Clinically, you're right: anything that affects the dopamine system will have clinically addictive properties (i.e. bingeing, preoccupation, anxiety, etc), and there's plenty of clinical research showing that long-term cannabis use can result in addiction. But what people sometimes mean by "addictive" is physically-painful and/or physically-dangerous withdrawal symptoms: nauseau, migraines, shaking, or even potentially death in the case of alcohol. Even heavy cannabis use doesn't generally result in those kinds of withdrawal symptoms.
Cannabis is very much psychologically addictive and hence the word pothead. If you don't know the pot culture and you don't see how these people can't have fun or pass a day without pot you will change your mind
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But you see the end result, not what could have been. The weed Grandfather could have got Alzheimer’s way earlier
Also, it's important to note that for Alzheimer's, the quality of the mouse models is suspect because the causation of the disease is still a mystery.
wondering to what degree finding the same outcome on a different animal increases the odds that it will work on humans. Maybe it ought to be an animal that also shares high genetic commonality with humans but in a way that is different from the lab mouse
Rodents are some of the closest mammals to primates in the evolutionary tree, so mice tend to be a very good models for human biological systems. There are some systems where there's virtually no difference between the two (I think the cardiovascular system is one, but I'm not really sure; biology isn't my thing). But there are some systems where the mouse system is very different from the human system, and the data you get from mice is practically garbage.
Which brings us to Alzheimer's. Mice don't get Alzheimer's. Instead, mouse models for Alzheimer's work by attempting to genetically induce something that we think might be how Alzheimer's develops in humans. Except, we don't actually know that much about Alzheimer's: the dominant theory, and hence the basis for mice models, involves amyloid plaque formation, but amyloid beta blockers have had ruinously expensive clinical failures which makes the theory rather difficult to believe. So anything that shows improvement in Alzheimer's in mice is pretty worthless as a result.
Which brings us to Alzheimer's. Mice don't get Alzheimer's. Instead, mouse models for Alzheimer's work by attempting to genetically induce something that we think might be how Alzheimer's develops in humans. Except, we don't actually know that much about Alzheimer's: the dominant theory, and hence the basis for mice models, involves amyloid plaque formation, but amyloid beta blockers have had ruinously expensive clinical failures which makes the theory rather difficult to believe. So anything that shows improvement in Alzheimer's in mice is pretty worthless as a result.
I think you are making a well reasoned point, but you might be overly kind to mouse models. The common ancestor of mice and humans lived before the dinosaurs went extinct, and humans (as well as other primates) have subsequently had very dramatic changes in genetics for nerve cells. We also live about 100 times longer, and Alzheimer's only ever shows symptoms around 30 years old at the absolute earliest, while a mouse used in experiments is rarely more than 6 months old. Widespread use of grant money to experiment on mice with the justification of researching Alzheimer's, without evidence there is reason to believe the experiment is isolating something meaningful to human expression of the disease, is literally fraud.
Is this how Mickey Mouse is so freaking big IRL and has been around since the early 20th century?
Nevermind; that’s probably not the type of mouse model you were talking about.
Nevermind; that’s probably not the type of mouse model you were talking about.
As mentioned by others but clearing beta amyloid and reversing cognitive decline in a mice has been done before.
Beta amyloid as a target has failed again and again, and the PDUFA for Aducanamb (mentioned at the end of the article) will likely end in rejection given the scathing adcom.
Beta amyloid as a target has failed again and again, and the PDUFA for Aducanamb (mentioned at the end of the article) will likely end in rejection given the scathing adcom.
After the whole mouse telomere fiasco, I'm weary of anything being cured in mice: https://www.youtube.com/watch?v=ve4q-1D_Ajo
CBD = Cannabidiol. The article doesn't mention it.
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Model is usually very different from actual disease...
Cannabis cures Alzheimers!
And cancer. And depression. And anxiety. And boring Friday evenings. Pending actual science in RCTs w/ sufficient statistical power of course.
I really hope we can get cannabis legalized so this we can get some efficiency in getting the peer-reviewed data on the table.
I really hope we can get cannabis legalized so this we can get some efficiency in getting the peer-reviewed data on the table.
Someone must have written a comedy around a randomized double-blind cannabis study. The experimental group keeps forgetting if they've taken their meds, taking a month's worth in a week. Researchers forget where they've put the blinding key, so they have everyone take urine tests to see which subjects are in the control group. All of the experimental subjects are too paranoid to show up for a urine test. Researchers resort to putting UV dye on some snacks in order to figure out who's in the experimental group.
....cannabis doesn't need Alzheimer's
Here is how they (generally) work: You take a mouse and cure it's Alzheimer's, right? Except mice don't live 70 years, and even if they did you can't wait 70 years for Alzheimer's mice to test drugs on. So you inject poison into the mouse's brain so it kindof has Alzheimer's like symptoms. Well, that's not even quite right, since you can't tell if a mouse has Alzheimer's like symptoms or just generalized brain damage (it's a mouse, you can't ask it if it can remember what year it is or what their kids names are, you can only see if they can remember which cup the cheese is under, well actually you can't even test that, just whether they behave like a healthy mouse would if it remembered, or some other really poor proxy for the sort of cognitive test you would use to diagnose Alzheimer's in humans) , but whatever, you have all these mice and someone is paying to inject them with poison so what can you do? Then you treat the poison damage with a drug, and get results ... but later it doesn't work on Alzheimer's in humans at all because human Alzheimer's isn't brain damage from poison injected into the brain.