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Cannabinoids remove plaque-forming Alzheimer's proteins from brain cells (2016)

https://www.salk.edu/news-release/cannabinoids-remove-plaque-forming-alzheimers-proteins-from-brain-cells/
I only had time to skim the paper. Notably, the effect is concentration dependent and required high concentrations of THC. The chart shows it really starting in the 0.1uM range and then taking off in the 1uM range.

I don’t know what levels are achieved during normal use but I did find some studies that successfully killed a lot of hippocampal neuronal cells after 6 days at 1uM range. So the levels of THC observed in this study appear to be in the same range where things start getting really disrupted in cells.

In other words, don’t expect to replicate these results with normal recreational use.

In vitro studies are not so great for establishing threshold doses surely?
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I suppose this might be why Willie Nelson is still doing pretty good these days...
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Reminds me of this classic: https://xkcd.com/1217/
New studies show that research is a leading cause of cancer in rats.
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There may not be many constants in this life, especially in this day and age, but I do find it humbling that "there is always an xkcd for that" holds true.
...is there an XKCD relevant to the fact there's always a relevant XKCD?
Can't have Alzheimer's if you don't have much of a brain left.
Can you explain the joke?
If the doses of cannabis required to cure alzheimers would be high enough doses to destroy the rest of one's brain, it makes this finding not very useful, similar to the idea of curing alzheimers by destroying one's brain/
But the studies are pervasive. For example, the (flawed) study that found that one cup of wine with each meal was healthier that no alcohol at all is still quoted today, and still "reproduced" in other studies that make the same claim but adding a clause of "given that you also [do good amount of exercise|eat very healthy|are in perfect health already]". Or the flawed studies that Soffriti and Belpoggi pushed (some of them didn't even pass peer review, but reached the public anyway) about artificial sweeteners and other things being carcinogenic: they basically feed mices with whatever they feel until they die, they look the corpses and if there is a tumor, eureka: what they put in the diet is the cause. Nobody took the studies seriously, except the public that now have a "scientific paper" that says Coca-cola causes breast cancer.

In this case some public reads "smoking a joint daily equals invulnerable to Alzheimer, science says so".

Yup. There's definitely a pattern and it seems like an obvious consequence of the structure of incentives.

If you make a product you can make a study that shows it has some kind of benefit in some specific way, even if it probably causes more harm in other ways that are less obvious, and then you can sell it. Media will spread around your study especially if it shows something that will be a bit click-baity, and any study or discussion of the possible downsides will get far less attention.

This is also why basically every edible plant has some article saying it's a "super food" etc etc.

Synthetic cannaboids were also studied as a possible analgesic and at the doses required it caused brain damage. Which is honestly disappointing because a general purpose pain killer that isn't opioid based would be a miracle.
although the study is often labelled irreplicable, i do still believe in rat park. opiates are not evil in and of themselves; rather, society forms a structure around which the use of opiates easily becomes more alluring than contributing to said society. consequently, those in chronic pain are often forced to suffer needlessly by being deprived of relief, so that societal productivity is maximized. the real miracle would be a fixed system, not the novel non-opiate painkiller suzetrigine. but apparently that is the next best thing.
Opiates form a quick and nasty addiction. People in constant pain (as in, 24/7 or even most of the day, every day) need to take ever increasing doses to get the same level of pain relief. You would be surprised how many folks are like that, and not only 70+ years old. It takes few weeks to form a lifelong addiction that can never be fully shed and will form a permanent crack or weakness in one's personality.

What all that, how can you defend opiates? Opinion of society is irrelevant here, they are absolute scourge if used enough, and nobody is immune.

treatment guidelines don't even stress the effect of opiates that is activation of corresponding receptors in the gut, causing water to be leached and chronic excruiciating constipation to result. if only people were told that drinking coconut water solves this problem without relying on pharmaceutical means. this is one example of opiates being demonized due to incorrect application.

i do argue that in the correct harness, opiates could be distributed to minimize unnecessary suffering at least somewhat - not 24/7, because literally any drug will result in tolerance (and debilitating physical side effects, something opiates lack) at that point. our current system is unsatisfactory - people are not taught how to take drugs correctly, and people exist in a system that naturally causes dopamine seeking reward systems to malfunction. while some are born psychologically weak, inherently leading to addiction susceptibility, society is expressly designed to produce such weakness in order to maintain the status quo. of course such an environment is not positively conducive to the dopamine flooding effects of opiates. i dont blame opiates for the system in which they exist.

regarding personality cracks, i still refer to rat park for the most part, saving brain resets such as ibogaine for extreme cases - our addiction inducing society (as a whole, not merely the opinions wherein) does not imply impossibility of rewiring addictions. regardless, some people think cracks are beautiful (ref. kintsugi).

do you argue that everyone should be instead placed on nsaids that destroy the stomach and liver, killing them earlier and objectively adding pain prior? is the current trajectory (that is, entirely depriving the suffering of effective relief, regardless as to their age bracket) for the best?

Yeah, people complain about opiates but even beta-blockers or antihypertensive agents have rebound symptoms if you stop taking them. People really just love to see others suffer instead of allowing them to use opiates.

NSAIDs are known to kill your stomach, your kidney, your liver, and your heart, whereas opiates do not. And they are ineffective for a lot of people's chronic pain, on top of that.

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I have been taking high-doses of opiates for years without any issues... without the need to increase doses. Without constipation-related issues. At times I go through voluntary withdrawal, however, but that is it. Am I ought to choose pain because opiates were made to seem like the devil?
i didnt really want to add anecdotal evidence to argue against the idea that nobody is immune ... but now that n=2 ... id like to also bring up the notion that schizophrenia is considered relatively benign (if not venerated) in some cultures, and the hallucinations experienced in those cultures are themselves benign ... whereas places like north america demonize schizophrenia, resulting in affected individuals being placed on chemical straitjackets, increasing their suffering purely due to societal influence ...
Surely there many substances that some people cannot do without. Treat opiates as just another one of those. They are cheap to manufacture. Addicts can hold down a job, pay taxes etc just like the rest of us. So why not?
We have dozens of pain killers which are not opioid based, what do you mean? From the top of my head NSAIDs can be used, and Metamizole for example is as effective as morphium.
you got nsaids, metamizole, acetoaminophen, duolexitine. And you got a couple of more that work for neuropathic pain. The biggest problem with nsaids is that they cause bleeding and kidney failure, ulcers hence can cause stomach cancer.

Here is a site you can use too see how most pharmaco therapy is lacking.

https://pain-calculator.com/calculators/osteoarthritis-pain/

Yes.

Very few painkillers that are not blood thinners. Paracetamol and canabinoids are a couple of rare exceptions.

My uncle broke his hip in his old age. He died shortly after because of the bleeding induced by painkillers.

Metamizol is banned in the US, so they've robbed themselves of that
What are your issues with opioid-based painkillers?
Sounds like this is more "Pouring bleach on germs kills the germs but it also kills everything else"
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Too bad we've had like a half-dozen putative Alzheimer's drugs that clear amyloid beta that turn out to do nothing to slow or prevent Alzheimer's.

Actually, I think even by 2016 we already had enough phase 3 drug failures that the amyloid hypothesis was severely called into question?

That's not true. Monoclonal antibodies are on the market right now which slow the progression of the disease (by removing amyloid).
AIUI, all such results are because the FDA has given up since aduhelm and said "well, if it clears amyloid, that's as good as slowing Alzheimer's, right?" despite the actual results on Alzheimer's progression being largely negative.
For what it's worth, early statins were originally cleared based only on the evidence that they lower cholesterol without longer term studies showing a reduction in mortality. Of course there is now plenty of evidence showing statins improve overall endpoints.
That’s true.

Similarly, there were other drugs that lowered cholesterol that didn’t show a significant reduction in coronary events. As we later learned, it’s not nearly as simple as “cholesterol bad.”

That doesn't sound like the same thing at all.
~~yes by 4 months. If I had AD i wouldn't bother with those treatments.~~ Sorry I missed the context you are right the fact that they slow AD by 4 months is a proof that amyloid plaques are part of the pathogenesis.
Or they have some other effect...
This appears to be dated 2016. Did the preliminary results amount to anything?
Yes but.. Amyloid-beta may be part of the innate immune system

https://news.harvard.edu/gazette/story/2010/03/alzheimers-as...

Do we still think clearing beta amyloid plaques will halt the progress of Alzheimer's? My impression is we're treating marker for the disease and not the cause.
Correct they don’t. It’s like removing the gravestones from the graveyard.
Man, too bad weed gives me bad panic attacks. Alzheimers is the scariest disease I know so maybe if the studies pan out in time and it becomes a standard preventative, I might consider trying again.

But somehow I doubt it will be found to be that effective.

Have you tried L-theanine? I also get panic attacks with weed, but L-theanine seems to help keep them at bay.
I have tried l-theanine, didn't do anything that I could tell.

But fortunately there's a much better solution for those of us who get anxiety from weed, it's called "don't smoke weed".

I've tried everything and I still get panic attacks. I used to love smoking a small hitter about an hour before bed. I've always had insomnia and that was the one thing that actually helped me sleep. When it was illegal, I loved it. I would smoke 2 or 3 times a week just for sleep, and I was healthy and happy. . . Because sleep is important, and I never wanted to take sleeping pills because dependency.

Now that it's legal and everywhere, I just get super fun panic attacks. I'm worthless, I'm failing as a parent, everybody hates me, you know, the normal anxiety attacks. Even Charlotte's Web that's SUPER low THC gives me panic attacks.

It's like my body hates it when I'm happy? I would give anything to be able to fix this problem.

Always thought that panic attacks were caused by too low CBD in regards to THC levels.

Saw someone literally suggesting keeping a CBD vape pen just in case of a panic attack. Or a friend using it for heart palpitations.

Wasn't the amount of THC concentration in resin seen as the indicator of potency? Then that amount was hacked through selective breeding, unbeknownst that not following with a complementary increase in amount of CBD will create an anxiety causing superdrug.

I experienced it once - on a party in a country where CBD strains are legal to buy by anyone, as long as they contain ~0%THC. And high quality high THC strains can be bought at a pharmacy with a prescription.

A friend rolled a 50%/50% joint, approx 0.5g total, and we proceeded to smoke it whole, just the two of us. I was surprised you could get that high without a shadow of a paranoia.

In legal states in the US it’s fairly easy to find commercial 1:1 THC:CBD products, among a litany of mega-potent THC-only options.

I never particularly cared for cannabis in general in the past–it didn’t give me panic attacks, but even a little bit made me feel kind of on edge. The 1:1 stuff is dramatically more pleasant.

Wow, Charlottes Web is such unique strain. I'm always on another planet no matter what the THC is advertised.

I feel like that strain is for EXPERTS. You can always mold it to the vibe you are aiming to reach in that present (ofc in the appropriate environments).

Do you feel like the anxiety just the cascaded result of ... "poor planning" over an extended, day-over-day staggering, sleep-deprived, period of time? I consider my self naturally the poorest of poor planners. My brain is just RAM with zero cache that i always imagine that I have. I've had weeks wiz by if I do not get on top of a fun, MJ propagandized base routine / schedule in place.

Apologies! Worse case, this could just be a swing and a miss. Empathies attempted.

Weed started doing the same thing to me in my mid to late 20s. What used to be relaxing suddenly turned into anxiety and negative thought spirals.

A couple years ago (around 40) I started taking a low dose antidepressant for unrelated reasons and noticed that the weed induced anxiety mostly disappeared. My guess is that for some people there’s a serotonin/anxiety component that THC can amplify, but that’s just speculation on my part.

Not suggesting antidepressants as a solution by themselves. They come with their own tradeoffs and I wouldn’t take them just for that. But it has been a pleasant side effect I didn’t expect.

I also get what I would describe as "near" panic attacks when I smoke (about once every two weeks, with friends). I realised that after about 15 minutes or so it cools down and I feel, perhaps, more relaxed than before I started. Purely anecdotal but I feel you. Maybe a bit of cooldown and good company helps with the paranoia.
So, I sort of get these from time to time, but I notice that it hits the worst when :

1. I've eaten like crap. Things too heavy I'm grease, processed food, and red meats. When I'm rating cleaner, I don't feel as panicky

2. If I feel the panic coming on, I HAVE to do some sort of aerobic exercise in that first 15 minute "induction" phase of smoking. Otherwise I'll carry the panic along through the entire session.

FWIW, YMMV

Yeah my defact is to run 5k at my pace (mild jog is fine), and just not use my screens + do not disturb mode, until i have a series of thoughts that invokes me to use my phone as a "lifeline" to quickly look up what I need to get to my next thought.

5km goes by fast! And orange juice tastes great after.

How low was the % of THC in the Charlotte’s Web?

Full spectrum hemp (~0%) definitely feels like the answer, here!

Have you tried edibles or another method than smoking?
I’ve found the edible thc (gummies/drinks) you get in non-legal states are much less panic/anxiety inducing. I’m not sure why but it probably has to do with CBD or something that is missing. It’s anecdotal but I’ve noticed it a lot. They also get you very high so I’m not sure how exactly they are getting around the legality requirement.
Pro: Salk Institute Con: Preliminary Research, In Vitro
Con: from 2016 w. no followup?
Salk? You mean the vaccine guy? /s

And also, apparently, the registered trademark?

> The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive.

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There are easily hundreds of compounds that can reduce beta-amyloid in vitro. This is a decade-old nothingburger.
There was another recent study showing that THC was creating false short term memories - like "I swear I told you that" - but never did.

Cannabis really needs a lot more study.

I have more trust on 40 hz ultrasound therapies.
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There was another recent study showing that THC was creating false short term memories - like "I swear I told you that" - but never did.
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...which is offset by typical dementia-like effects, other cognitive impairments in chronic weedos.
Anecdotally, when I'm feeling scattered and foggy, when I take a big hit off of my vape pen, I go through a period of noticing how shaky my appendages are, and go through what feels like a physical process of the sensation of my mind "unwrinkling" or unfurling. I often wondered if something was being cleaned out in my brain because I usually feel a lot more calm and still afterward, thoughts more collected.
Acetylcholine receptors, at minimum.
Get stupid now to avoid cognitive decline later? Not sure I like that tradeoff...
Not really sure what you mean, I saw people on 10mg THC wring crazy code in a crazy speed. Some of them need it to be able to focus and think clear. Drugs never work "one way" for everybody. And its not only people its many things that affect how they work (setting, culture, education etc.). And if you think man kind does not need any drugs (including alcohol), if you look at it from a historic perspective we might even need it.
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As opposed to getting stupid now and getting cognitive decline later?
One adapts to it over time like any other state. Homeostasis is a blessing and a curse.
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And yet, has anyone ever claimed regular marijuana use improved their memory?
Ok fine, I'll chime in.

No, it has not improved my memory. Though, I am not really certain anything does. At least, not permanently. Though, I will say the effects on memory are rather complex. Some diminished abilities in some domains, but oddly some enhancements in a select few domains.

I am 'neurodivergent' apparently, so my experiences might not be worth much.

Remove them and replace them with...Doritos?
I seem to have touched a nerve.

In my defense, it may have been a stupid joke but it's not as stupid as trying to prevent brain damage by taking cannabinoids at levels known to cause brain damage.

They can’t all be winners, right?

Here. Take my upvotes to balance it out a smidge.