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

167 points by anjel a day ago on hackernews | 104 comments

[OP] anjel | a day ago

Pro: Salk Institute Con: Preliminary Research, In Vitro

whycome | a day ago

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.

magospietato | a day ago

Con: from 2016 w. no followup?

cdata | a day ago

This appears to be dated 2016. Did the preliminary results amount to anything?

mawise | a day ago

rusakov-field | a day ago

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.

dmorgan81 | a day ago

Have you tried L-theanine? I also get panic attacks with weed, but L-theanine seems to help keep them at bay.

Loughla | a day ago

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.

karim79 | a day ago

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.

R_D_Olivaw | a day ago

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

sam1r | a day ago

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.

squigz | a day ago

Have you tried edibles or another method than smoking?

johnisgood | a day ago

I have not done weed for ages, but while smoking would always give me anxiety, vaping much less so.

Loughla | 17 hours ago

Yes and they cause panic attacks, but they last even longer. So that's cool.

wafflemaker | a day ago

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.

neom | a day ago

macNchz | a day ago

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.

Loughla | 17 hours ago

So Charlotte's Web is super high CBD and extremely low THC. That's why I picked it. And it still makes me have anxiety attacks. It's very upsetting, as that was the one thing I could do to relax and sleep, and now even that is ruined.

Maybe it's just getting older? Who knows. I just wish I could get high a couple of times a week so that I sleep more than 2 or 3 hours.

rimshot | a day ago

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.

sam1r | a day ago

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.

Loughla | 17 hours ago

Charlotte's Web is what I picked because it's so so so low THC content. I'm usually pretty on the ball, and the things I have panic attacks about aren't things that actually bother me when I'm sober. It's like I become hyper critical of myself and over analyze every decision and conversation I've ever had. It's not good.

DANmode | a day ago

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

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

Loughla | 17 hours ago

It's like 0.3%. so pretty much as low as you can get while still having some THC.

Does hemp have the same relaxing qualities?

DANmode | 14 hours ago

Good hemp does.

Terpenes are the secret to cannabis.

Most cannabis has terpenes as a consequence.

Some cannabis has terpenes as a priority. This is the best cannabis.

The “essential oil” of the cannabis plant.

Loughla | 13 hours ago

Any suggestions on the hemp or strains of THC? Hemp products make me kind of uncomfortable just because of the lack of regulation. God only knows what's in some of those things. Anyway, any brand recommendations?

DANmode | 10 hours ago

Checked the brand I used to use when I needed it - they’re no longer selling hemp flower - just THC A.

Look for brands with lab tests that include terpene levels, and mycotoxins/solvents, for best results!

esperent | a day ago

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".

smugtrain | 23 hours ago

Abstaining is not a cure for rude smugness, apparently

esperent | 11 hours ago

Nominative determinism via HN username. Your name has smug in it, and you go around seeing smugness where there is none intended. Sounds like a struggle but who am I to judge.

dyauspitr | a day ago

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.

doublerabbit | a day ago

THC is the compound that gets you high. CBD is the governor that restricts the high.

If you end up smoking high percentage THC with little to no CBD, those who with tactile brains will enter a state of negativity. Anxiety, paranoia et cetera.

Essentially just roll CBD leaf only with your main THC leaf and this should equal the balance but again this is all anecdotal and myself as experiment.

genthree | 20 hours ago

Try really low doses.

I hate being truly high, but a weed "buzz" is great for falling asleep, especially when ill (I often suffer more from severe lack of sleep than from any of the other effects of whatever common virus or bacterial infection I manage to catch). It doesn't take much for a lightweight (a status I have carefully maintained) to reach "buzz" territory, and only a little more to reach "properly high" territory (which, again, I find rather unpleasant).

I'd suggest edibles and starting at 2mg, max, for a first attempt, working up 1mg at a time (in a totally different session, on another day!) until desired effect achieved. Like I've been at this a while and a 10mg gummy, which is a common single-gummy dose size in many states, will take me past where I ever want to be. 5ish is about right for me, maybe up to 8 if I need a stronger kick for some reason (like, say, I'm sick and need to get high enough to sleep most of the night despite significant sinus discomfort or throat pain)

FWIW I also doubt the anti-Alzheimer's stuff will pan out, or if it does, it'll be some targeted therapy with specific chemicals, which won't look a lot like any products from a dispensary.

MarkusQ | a day ago

Remove them and replace them with...Doritos?

MarkusQ | a day ago

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.

Dansvidania | a day ago

They can’t all be winners, right?

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

ProjectArcturis | a day ago

There are easily hundreds of compounds that can reduce beta-amyloid in vitro. This is a decade-old nothingburger.

Aurornis | a day ago

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.

mrosett | a day ago

Reminds me of this classic: https://xkcd.com/1217/

farmdawgnation | a day ago

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.

SeanAnderson | a day ago

...is there an XKCD relevant to the fact there's always a relevant XKCD?

eclecticfrank | a day ago

simonh | a day ago

New studies show that research is a leading cause of cancer in rats.

jijijijij | a day ago

On a serious note: Humans are considered an oncogenic species. https://www.nature.com/articles/s41559-018-0558-7

(You somehow get the full article via https://www.iflscience.com/humans-may-be-causing-cancer-in-o...)

jojobas | a day ago

Can't have Alzheimer's if you don't have much of a brain left.

throwaway27448 | a day ago

Can you explain the joke?

lithocarpus | a day ago

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/

Spivak | a day ago

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.

laserdancepony | a day ago

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.

Muvasa | a day ago

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/

srean | a day ago

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.

hermanzegerman | a day ago

Metamizol is banned in the US, so they've robbed themselves of that

johnisgood | a day ago

What are your issues with opioid-based painkillers?

thin_carapace | a day ago

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.

kakacik | a day ago

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.

thin_carapace | a day ago

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?

johnisgood | a day ago

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?

thin_carapace | a day ago

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 ...

analog8374 | 22 hours ago

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?

otherme123 | a day ago

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".

lithocarpus | 19 hours ago

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.

xeromal | a day ago

Sounds like this is more "Pouring bleach on germs kills the germs but it also kills everything else"

KennyBlanken | a day ago

I suppose this might be why Willie Nelson is still doing pretty good these days...

aswegs8 | a day ago

You might have replied to the wrong comment. OP implied it would have no impact

vercaemert | a day ago

The joke is that Willie Nelson has used very high concentrations simultaneously frying his brain cells and staving off Alzheimer's.

wavefunction | a day ago

Willie Nelson is pretty sharp for his age. I compare him to the much younger President of the United States who blathers absolute nonsense constantly despite no known history of cannabis use and a claimed history of abstaining from all substances.

red-iron-pine | a day ago

> claimed history of abstaining from all substances

[rolls eyes]

lots of anecdotal evidence suggests donnie t like stimulants, esp. the kind that you can put up your nose.

butlike | 18 hours ago

It's stress. I'm convinced of it. Little old lady is smoking cigars at 105 years old because she's stress-free. Willie Nelson is looking sharp for his age because he's low-stress. If it helps reduce your personal stress, perhaps...PERHAPS, it's a good thing.

__alexs | a day ago

In vitro studies are not so great for establishing threshold doses surely?

malfist | a day ago

In vitro is great for publication though. If I out bleach and Alzheimer's plaques in a petri dish I bet I could publish that sodium hypochlorite treats Alzheimer's

sixeyes | a day ago

I'm pretty sure 0.1 µmol per liter and such absolutely does happen in recreational use. (Recreational use is toxic, destroys memory, etc.)

rolph | 13 hours ago

quick back of the envelope:

this would require 3 joints of ~ 300 mg cannabis at ~ 30% THC content.

the legendary MTF strain regularily trumpets a 25-30% THC content.

now if bioavailability is 30% that means you need 9 or 10 joints to get a 1 micro molar total dosage. that dose is distributed across body mass.

at this point, i cant say i could conceive of anyone smoking basically an 1/8 ounce of MTA in one day, let alone at one sitting, and doing that for 6 days in a row sounds frightening, not recreational.

https://en.wikipedia.org/wiki/Tetrahydrocannabinol

bitwize | a day ago

Get stupid now to avoid cognitive decline later? Not sure I like that tradeoff...

SecretDreams | a day ago

As opposed to getting stupid now and getting cognitive decline later?

hirvi74 | a day ago

One adapts to it over time like any other state. Homeostasis is a blessing and a curse.

carlos22 | a day ago

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.

bitwize | a day ago

Unfortunately I know how THC works on me and it's not very desirable.

kakacik | a day ago

Less mental capacity for structured thoughts during/after getting high is normal, as is massive increase of creativity. Mind wanders a lot. The effect goes away completely in a day or two but there is no end how high can user spiral into anxiety trip from expecting weird stuff and losing some control.

Rather frequent use (as in not every day all the day but lets say couple of times a week) can have some decline but IMHO its still temporary. If the brain is already used to lower learning and complex analysis activity then it will be compounded but otherwise it shouldn't. I sometimes fall here, and I integrate internal banking systems for a living for 2+decades in very competitive place plus raising family and have mortgages, so no shortage of stress. Any miniscule decline is more than compensated by relief of stress and some giggly happiness, plus that massive creativity spike which allows me to catch up with stuff slowly sliding out of focus (and then biting hard like bureaucracy, taxes etc). Literally subconsciousness sliding notes underneath the doors of my mind, topics often pop out of blue, in such frequency that I sometimes struggle to keep up and take notes since next one with higher priority comes and then next one.

Full on stoner - thats a goner, if we talk decades of use, I think. YMMV. But - I've met folks who had periods of life where they smoked all the time every day, for 5-10 years, usually teens (where I would say folks are very vulnerable since brain is still evolving). All are fine now in various roles in their lives.

lostmsu | a day ago

I would like to see the "crazy code" in question to take this seriously. Were you high on THC at the time as well? That would be a more plausible explanation of the perspective.

laughing_man | a day ago

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.

Retz4o4 | a day ago

Correct they don’t. It’s like removing the gravestones from the graveyard.

criddell | a day ago

jcranmer | a day ago

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?

nikkwong | a day ago

That's not true. Monoclonal antibodies are on the market right now which slow the progression of the disease (by removing amyloid).

jcranmer | a day ago

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.

riskassessment | a day ago

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.

simulator5g | a day ago

That doesn't sound like the same thing at all.

AuryGlenz | a day ago

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.”

Muvasa | a day ago

~~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.

coryrc | a day ago

Or they have some other effect...

Retz4o4 | a day ago

Zunveyl

colordrops | a day ago

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.

DANmode | a day ago

Acetylcholine receptors, at minimum.

anonnon | a day ago

And yet, has anyone ever claimed regular marijuana use improved their memory?

hirvi74 | a day ago

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.

edoceo | a day ago

There was another recent study showing that THC was creating false short term memories - like "I swear I told you that" - but never did.

krupan | a day ago

I see what you did there posting this comment twice. Well played

edoceo | a day ago

Mistake, too late to delete

edoceo | a day ago

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.

miika | a day ago

Yes but.. Amyloid-beta may be part of the innate immune system

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

anthk | a day ago

I have more trust on 40 hz ultrasound therapies.

doublerabbit | a day ago

Why not both, get high while listening to 40 hz ultrasound.

meetpaleltech | a day ago

...which is offset by typical dementia-like effects, other cognitive impairments in chronic weedos.

oliyoung | a day ago

"reefer madness" has put legitimate research of that plant back immeasurably

pstuart | 21 hours ago

For those interested in this and preventative measures, there's been reports about lithium helping prevent Alzheimer's: https://hms.harvard.edu/news/could-lithium-explain-treat-alz...

Standard disclaimers apply.