Microdosing LSD for Alzheimer’s proves safe in early human trial | Hacker News Reader

Microdosing LSD for Alzheimer’s proves safe in early human trial

newatlas.com

214 pointsfutureguy107 comments

The most interesting thing about this study for me is that they're actually studying LSD at all.

For years now, the main psychedelics that were studied in clinical trials were psylocibin and MDMA, partially because LSD was deemed to have too large a stigma attached to it from years of negative media exposure. Now I guess we've moved beyond that.

What would be really interesting is some studies of the people who are in positions of authority to approve or disapprove such studies. What are their attitudes towards drugs in general and various psychedelics in particular? I guess we're seeing indirect evidence of their attitudes in the approval of such studies, but it would be interesting to see more direct and comprehensive evidence.

> partially because LSD was deemed to have too large a stigma attached to it from years of negative media exposure

Partially, but the main reason is that it’s too expensive to run studies where you need to pay people overtime to be there for 16 hour days.

I don't think this is a factor for microdosing studies.

The effects of LSD seem to persist for similar amounts of time independent of dosage. The drug has a halflife for urine and blood sample detection, but that does not affect the time that the user feels the effects of the drug.

https://www.popsci.com/lsd-gets-stuck-in-brains-receptors-se...

> I don't think this is a factor for microdosing studies.

It's still illegal for folks to drive home with LSD in their system even if it isn't impairing them, so I'd think this would be a challenge in getting IRB approvals.

There are medical limo services specifically for this, but I concede they get very pricey.

> What would be really interesting is some studies of the people who are in positions of authority to approve or disapprove such studies. What are their attitudes towards drugs in general and various psychedelics in particular?

One thing I've learned about people over the years is that they rarely change, even in the face of evidence and solid persuasion - I speculate the reason these studies are being approved more now today than before is not because of reasoned policymaking, but simply one of demographic shift in the public-sector: Those who bought-in to the anti-psychedelic hysteria of the 1960s will have almost entirely aged themselves out of the DEA, university research oversight boards, and the pharma industry. In fact, as members of Gen X themselves are _aging-in_ to positions of power and decision-making we'll see things start to open-up.

Or, as Max Planck succinctly put it: “A new scientific truth does not generally triumph by persuading its opponents and getting them to admit their errors, but rather by its opponents gradually dying out and giving way to a new generation that is raised on it.”

Often summarized as "Science advances one funeral at a time".

_Society_ advances one funeral at a time.

...and that's just depressing :(

That's really just the cycle of life forcing itself on us whether we like it or not. Sometimes humans collectively forget that we're biological entities first and foremost, with all the limitations and imperfections that come with that.

Possibly, the most damaging human trait is arrogance. It causes us to get trapped inside a box, unable to look outside for other approaches.

Or more likely the same thing will happen. People always think old people are useless and that young people will change everything. But in reality only a few people of any generation are willing to change how things are done (and that can happen at any age). The rest won't take any chances and perpetuate the sameness. Then the next generation will come along and will think, finally the old people are done and we can do things right. Yet the few will still change the world in defiance of the many.

If you're reading this and thinking about trying microdosing, let me summarize for you - unless you have chronic depression or anxiety, this isn't really worth it. You'll have a harder time actually focusing and getting work done.

If you do have chronic depression / anxiety though, and it's affecting your life in a persistently detrimental way, it might be a really effective Aspirin against it (i.e. it's not going to Cure it, but it will relieve it). LSD does this by interrupting Rumination, the shitty thoughts in the very back of your mind that loop during depression / anxiety.

Breaking this cycle lets you have some relief, and might help you get your head above water enough that you can start to address some of the Bigger Problems, without some of the pretty significant drawbacks of SSRIs (as well as working nearly instantly, as opposed to having a month+ ramp-up)

The looping of shitty thoughts is the exact thing I have to fight against in a psychedelic state. It's weird how things like this seem to work out. Giving speed to a person with attention issues, yet to a normal person it makes their thoughts run rampant.

I always thought it was curious seeing a friend with ADHD taking adderall seemed to calm him while it had the opposite effect on me.

By definition, microdosing is taking a sub-perceptual dose.

So if you're noticing any effect, like having a hard time focusing, you're taking more than a microdose.

Sub-perceptual in what sense? In escalating order...

You can't tell any obvious distortion in your perception of reality? [This is the meaning I usually hear discussed].

You can't look back over the past day and say "hm, that was different from when I was not dosed-- I was a little less effective".

You can't tell any difference over the past 6 mos of microdosing?

You can't tell any difference between a microdosed and placebo group in an RCT?

There is no difference at all between microdosed and placebo in reality?

In the end, if we can't notice some difference somehow, why bother? ;)

You're not supposed to notice any perceptual differences while the experience is happening. The whole point of microdosing is to experience the positive benefits and changes, over time, without any of the overt psychoactive effects commonly associated with larger doses of psychedelics.

And if someone tries microdosing for a few days and decides that, in retrospect, they were a little less effective and focused in their work, like the great-grandparent suggests? I don't think the immediate criticism of (paraphrased) "It's not microdosing if you notice a fall in work efficacy, because you noticed it" is fair.

Sounds like you agree the threshold of microdosing is defined by the first question, rather than the subsequent ones.

That is, one wants a dose that doesn't make a difference moment to moment and doesn't cause overt psychoactive effects, but does cause some degree of effect noticeable in retrospect.

That's certainly entirely possible. Everyone's neurochemistry is different. I'm not sure that "a few days" is enough to truly assess the situation, but it's a good start. Perhaps a slightly different dosing regimen may still benefit such a person. As well, it's entirely possible that abstinence is best for that person. No way to know that going in, though.

And yes, I do. I also believe that approximate threshold doses (enough to feel a mild "elevated" state, but not to the level of warping one's perception of reality) have benefit as well. The big trips do too, but a threshold dose or less can allow one to still be able to function in a normal way, just with an increased sharpness of mind and an ability to focus easier.

I'm speaking from personal experience here, of course. The thing about psychedelics is that YMMV, which is why being mindful of what we do know about psychedelics is so important.

What about some research that microdosing increases neuroplasticity?

It may be a good benefit, if doctors manage to combine it with therapies for adults and they gradually rewire their brain addressing some inefficiencies, PSTD, or even brain damage.

Sorry, if I sound naive and anti-scientifical, I have no personal evidence for that and am not a neuroscientist. I recently was impressed by the stories in the book “The brain’s way of healing”.

> It may be a good benefit

It may. Or it may not. That's really the problem with acting on research that isn't commonly accepted. I still run into people who believe that cooking in aluminium pots causes Alzheimer's. Since the result appeared in a respected paper and was widely reported on, it lodged in the minds of the public. Later retractions had difficulty dislodging the idea.

Especially if someone has a particular bias, it's easy to find an amount of research that confirms that bias (confirmation bias). When you present the material that you have found, it can be incredibly impressive. I have found that if someone has an incredibly impressive list of research that backs up a theory that isn't widely accepted, it is almost always a case of confirmation bias. Of course, sometimes the widely accepted notion has just not moved in that direction yet. The problem is that without being a true expert in the field it's essentially impossible to tell which is which.

It is an unfortunate truth when studying very complex systems. Progress is made slowly with many arms reaching in different directions. People make promising leads, only to eventually find they don't lead anywhere. We often get stuck not knowing where to go. Sometimes when we find the answer, it turns out it was sitting under our noses all the time. It's just the way it goes.

Add ADHD to that list. I and a few friends with similar meatware stacks have found it very effective. I don't have hard data, but after one 3 month period I found a significant correlation with micro days and hours worked, number of LOC committed, and quality of that code.

I think anyone neurodivergent stands to benefit, and if they are not, well, sounds like they have a decent handle on life already.

> Breaking this cycle lets you have some relief

Edit: That's not to say people living a content life would not benefit from doses, micro or otherwise. It's just probably much harder to detect in a clinical setting.

I found microdosing greatly improved my productivity and ability to focus. I think it may be dose dependent and one would have to dial in to their appropriate dose. Also, the type of work one is doing may be an important factor.

In my experience, microdosing will do a great job at convincing you that you are extra productive and creative, but you don't end up actually getting anything done - you're just way more excited about it. Being excited is a Good Thing, but imho there are more effective ways to be productive

Just as a side note for those who think that it is the first step in recognizing the benefits of microdosing for healthy people, that study shows nothing.

First, it just shows that it is safe. It is expected, LSD is one of the safest drugs out there. I don't think there is a single verifiable instance of someone dying from LSD poisoning, even considering massive overdoses. And because we are talking microdoses, it is not like people are going to experience traumatizing bad trips.

The real question is whether microdosing LSD is better than a placebo and we don't have the answer yet.

And even if it is, the goal here is to treat Alzheimer patients, and that LSD proves effective doesn't mean healthy people will get benefits. A good example would be ADHD, which is treated using amphetamines. While these drugs will make healthy people high and overexcited, it will help ADHD patients calm down and focus.

I am very happy that LSD gets some serious attention, but it doesn't mean it is some kind of panacea.

> While these drugs will make healthy people high and overexcited, it will help ADHD patients calm down and focus.

It is my understanding that nootropics like Adderall are widely used outside of the ADHD-diagnosed population for their use in boosting productivity tasks in otherwise-healthy adults (see their popular use by students at colleges), and also for their high.

It’s strange to me to hear speed described as a nootropic, although I note that Wikipedia does list it as one. If amphetamine are a nootropic, does cocaine count?

I thought nootropics were supposed to have positive long-term physiological benefits. Amphetamine is a performance enhancer and maybe even a cognitive enhancer (evidence says otherwise) but it's definitely not nootropic.

I’d have thought so too, but Wikipedia describes it as one, so who knows

If a substance improves certain cognitive metrics in healthy adults, then it qualifies a nootropic, even if it has harmful side effects. Purported nootropics are often also marketed as, or alongside, purported life extension products. Maybe that creates some confusion about what nootropics are.

Nootropics are drugs that boost cognitive performance: https://en.wiktionary.org/wiki/nootropic

From your link:

>and possesses very few side effects and extremely low toxicity.

Only if you take the pharmacological definition. The medical definition is exactly as I said.

What a weird hair to split, pharmacology is a part of medicine.

The "medical" definition is incomplete.

The military has used speed to boost the performance of soldiers in war for almost a century, especially when in extended combat situations to stay alert and awake beyond an ordinary sleep cycle. The Nazis famously gave pep pills to their Panzer tank crews during the 'blitzkriegs' of Poland and France, and many militaries have given it to bomber pilots on extended runs, including the US.

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

> While these drugs will make healthy people high and overexcited, it will help ADHD patients calm down and focus.

And beyond that, this simply is a misconception and myth perpetuated by uneducated people. ADHD patients calm down when they take Adderall because they’ve been on it for years and have a tolerance. That’s just what happens. You don’t get the exact same euphoria that someone who takes it monthly feels. The underlying mechanism of action is the same for all humans.

My understanding is that ADHD patients are in a constant unsatisfying "underexcited" state, so they will do anything to find exciting things to do. Amphetamines pulls them up to normal levels.

Give the same substance to someone already at a normal level and he will become overexcited.

Just like putting weights on a scale can balance an unbalanced scale or unbalance an balanced scale.

I'm in a weird position of taking both ritalin and celexa. It makes me both anxious and focused.

I had to quit Ritalin in year 11 because the anxiety was completely fucking ruining my social development, regardless of whether it was useful to get good grades. I'm unmedicated now (30) and still in some ways quite a difficult human to deal with due to erractic behaviour and unreliability and disorganisation, however, I don't think I could go back to the ritalin man.

Ritalin (methylphenidate in general) is a rough one, cause of its stupidly short half life (as short as 90min in some). On top of that, most extended release systems for it are garbage. Sure on average, the blood plasma level graph is smooth, but you look at individual profiles, and some individuals have way higher peak amplitudes. In my experience, MPH, even the ER/concerta stuff, thrashes your mental state too much to be productive. I actually had more stability dosing slivers of MPH IR every hour, but man, that's tedious, it's easy to miss, and once you drop, it's not the same, even if you get back to therapeutic range.

I like that explanation especially the first paragraph.

I don’t understand pharmacology well enough to really know exactly what’s going on, but I’ve always thought today’s ADHD drugs are extremely broad, perhaps even crude solutions to a poorly-understood condition.

Kind of a super broad-spectrum antibiotic versus a narrow-spectrum antibiotic. Today, my (non-medical) understanding is essentially the same as yours, and that we use Adderall and other stimulants to do what you say - push them to the normal side of the spectrum - but at its core it's just messing with dopamine levels.

Having ADHD and being medicated for many years, it's not like the feeling of "being on a drug" ever goes away completely. It's not completely benign like, e.g. taking an allergy pill. It still curbs my appetite, so I have to be careful about scheduling doses (always eat before). There's a bunch of personality changes when the drugs are in my system, mostly stuff that makes you want to just work "heads down" and not talk to anyone, sometimes that's great, sometimes it's not. I wonder if I am less emotional and am more selfish because of being on it so long, I can't imagine telling someone "I miss you", for example, that just seems like an overly-sensitive emotion that I'm not capable of producing. Especially not in a world connected by iMessage and the Internet, where everyone seems like they are right beside you, even if they are thousands of miles away.

Not sure where I'm going with this, but I guess what I meant by "broad action" is that we are kind of killing one person by carpet-bombing. I wonder if in the future we'll have meds that work much better with less side-effects.

Maybe we even have them now in the form of the non-stimulant options, but my doc did not sound enthusiastic about switching from stimulant to non-stimulant ADHD meds.

Wow that first paragraph is an explanation I never heard before but nails the concentration part of ADHD

>This simply is a misconception and myth perpetuated by uneducated people

I think it's less of a misconception and more of the fact that people whom stimulants noticeably calm down are a lot rarer than people with ADHD, if that makes sense.

I know personal anecdotes are not data, and I've not taken Adderall itself, but when I got prescribed Vyvanse (lisdexamfetamine) for the first time, and pretty high dose at that, the difference was immediate and notable. I went from being anxious, waking up a couple of times a night, generally sleeping badly when I did and always feeling tired to getting a full 8 hours of restful sleep and a nap during the day if I wanted (despite taking the strong dose of Vyvanse) and being a lot less shaky during the day. Before that, I had never taken any stimulants besides coffee, which never seemed to do anything for me anyway so I wasn't one of those people who "couldn't function without their morning cup of joe" so I skipped it most days because I wasn't feeling up to breakfast.

This has been the greatest change in quality of life for me and if you had told me 5 years earlier that I would feel this way I wouldn't have believed you.

Improved quality of sleep aside, I don't really get euphoria when I'm taking stimulants. If I had to compare it to anything, when I started taking ADHD meds (I started with Straterra but it was only partially effective) it was like no longer being drunk.

> And beyond that, this simply is a misconception and myth perpetuated by uneducated people. ADHD patients calm down when they take Adderall because they’ve been on it for years and have a tolerance.

Hmm I have to disagree here. Even with my first dosage of Concerta (Methylphenidate) on no tolerance, I started feeling calmer. Like a lot of the chatter in my head got muted and I stopped jumping from thought to thought like a pingpong ball. This experience matches with other friends that have ADHD.

On the other hand when I give them out to friends for trying more often the other person ended up not being able to concentrate due to restlessness or wanting to do a lot of things at the same time (kind causing similar things that it gets rid of for me)

> ADHD patients calm down when they take Adderall because they’ve been on it for years and have a tolerance.

Speaking of myths, this is wildly incorrect. I've now been on methylphenidate -- AKA ritalin -- for a couple months. I do not and have not ever experienced a high or otherwise any euphoria. Partially this is indubitably because of the relative low dosage and low bioavailability. But partially it's because ADD makes me react differently to it.

There's roughly three effects I experience. Primarily it's way easier to stay focussed. The only side-effects I've been experiencing is some feelings of stress towards the end of the effective time of a dosage and some slight muscle twitching in my leg.

Anecdote aside, one of the possible side-effects of these sorts of medication is "a rushed feeling". Most people do not get this side effect, and if they do it's a cause for looking at different medication. It's definitely not the case that that's just something you build a tolerance to. Tolerance building is a thing, but it applies to the beneficial effects just as much as it applies to the side effects.

Agreed. I have built a tolerance to it before but know that I do not have ADHD. My friend who certainly does reacts to adderall differently than I do. We have discussed it in detail and seem to be effected differently despite taking similar doses daily.

This far beyond my understanding, but ADHD patients appear to have an imbalance between dopamine and norepinephrine in the mesocorticolimbic dopamine pathway and the locus coeruleus-noradrenergic system. There is more to this of course and I'm sure I botched even that part. Regardless, the point is that these medications actually treat their underlying issue instead of overdriving the same systems. Tolerance is mostly irrelevant in this regard as people without ADHD do not have these same differences which means they do not react to the drug in the same manner. Simply put, these medications tend to make ADHD patients more calm and focused and normal people tend to feel "tweaked".

In a way, calm and focus are the same thing as tweaked, but I guess you'd have to be on it to understand what I mean by that.

Well, there is that story of an elephant taking 300 milligrams (not micrograms) and dying, which might or might not have been caused by the acid itself...

https://en.m.wikipedia.org/wiki/Tusko

Enough of anything can be hazardous.

"I don’t know anybody that’s ever died from smoking pot. Had a friend of mine that said a bale fell on him and hurt him pretty bad, though." - Willie Nelson

how would you even make 300mg of LSD? the precursors like ergotamine are extremely hard to get, especially in that kind of quantity

Depends on your location. I know that in Germany the derivatives like 1P-LSD or 1sP-LSD are not banned.

They are in a zone where you can buy them for “scientific research, not human consumption”, but do not trust me on that: I did not try it and am not a lawyer. I have friends that did that exact scientific research, and they basically received them in a mail from some website.

Just googling “LSD Deutschland bestellen” shows established shops with range of options.

>First, it just shows that it is safe. It is expected, LSD is one of the safest drugs out there.

Yes, certainly. A drug that can trigger a psychosis after taking it only a single time and that can give its users persistent hallucinations[1] is one of the safest drugs out there. The drug propaganda gets completely out of control.

Edit: Not to forget that taking LSD can permanently change your personality.[2] In most cases these changes may appear positive, but there is probably a potential for permanent negative changes.

[1]: https://slatestarcodex.com/2019/09/11/lots-of-people-going-a...

[2]: https://link.springer.com/article/10.1007/s00213-017-4733-3

Yep over the years I have met many people with the story about the person with latent schizophrenia who switches from functional to extremely ill after a single LSD trip. I knew someone like this in my youth, and have since heard about many other cases. One of the more famous examples is the musician Daniel Johnston.

LSD is powerful and not to be messed around with lightly. Yes, it's not heroin or meth. But it's a powerful chemical whose effects can vary wildly from person to person and setting to setting.

And I totally agree... But I meant it in a "not a poison" sense, meaning it won't kill you. That's why I explicitly mentioned "LSD poisoning". I should have been more clear.

I have heard of HPPD and looked it up, but found nothing conclusive. I don't deny that it is real but we really don't know much about it. One problem is that we know that it happens to LSD users, but that's usually not the only drug they use, and due to its illegal nature, we are not even sure that's really LSD. There are LSD substitutes like NBOMe that have similar effects but are much more unsafe. To my knowledge, none of it happened in controlled studies.

I agree with the changes in personality that can be negative.

But an important part is that the study is about microdoses. Doses that are not enough to give you hallucinations. My personal theory is that the life-changing effects of LSD come from experiencing the hallucinations. These can be really intense, they are nothing like you ever felt before, and unlike dreams, they are memorable. And like any intense experience, they are bound to affect your life, for the better or for the worse. In fact, "flashbacks" have a lot in common with PTSD, so much that I think they really are PTSD, with the (usually bad) trip being the traumatic event.

But microdoses don't create these kinds of intense experiences. So combined with the fact it is essentially non-toxic for your body, I am not at all surprised that it passed all the safety tests. The really interesting part will be about effectiveness.

MKUltra and similar programs brought LSD into certain academic/nerd circles many years ago and broke their brains. This is why you are being downvoted (ironically enough).

Any studies that show an increased risk for psychosis after a single dose?

How I saw it explained is that LSD shuts down a system in the brain.

Once it's off, it can't be any more off, so nothing special happens with an overdose.

> and that LSD proves effective doesn't mean healthy people will get benefits

There have a number of studies showing that psychedelics (often psilocybin, which has similar effects to LSD) can have significant benefits for healthy people in a carefully managed setting.

For those skeptical of psychedelics being used for anything but recreational situations, I recommend a recent book How to Change Your Mind by Michael Pollan.

The author goes through the story of different psychedelics (including LSD) and shows how impressive some of the experiences and studies are. It did change my view completely. This article [1] also summarizes how close we are to use them for medical purposes.

[1] https://blogs.scientificamerican.com/observations/psychedeli...

Reply All did an episode on microdosing on LSD, and its effects/benefits: https://gimletmedia.com/shows/reply-all/2oh933/

No matter how you spin this, the vast majority of people get depressed from environmental settings and long periods of stress. Very people are born with a depressed mind.

For me, this is treating symptoms where we should focus on curing the fucking reasons why people get so depressed.

Sure, let's eat some more drugs - like we don't eat enoigh of that shit. The whole notion of taking drugs to become sane is fucking insane and ridicoulos.

Sleep, workout, and eat properly.

For the people that are real sick with depression - I feel with you, I really do! And if LSD helps those people, or any other drug does, just go onboard.

I don't think we've historically lacked motivation alpng those lines. AFAIK humans have been trying to address the valid reasons to be depressed for (at least) thousands of years. We've also been ingesting chemicals as a temporary hack for about as long.

Sleep, exercise, and proper nutrition won't solve long term sources of stress or depression stemming from environmental settings. Yes they are excellent habits to have, but I'd wager they only make the symptoms of the aforementioned issues slightly easier to deal with.

I'd argue you probably need to have more widescale societal and cultural reforms to get rid of the sources of most of those problems. Substantially better healthcare and higher education to reduce loan burdens, shorter working hours and commutes to have more time to spend with family and friends, etx.

https://www.psychologytoday.com/us/blog/exercise-and-mood/20...

> well-conducted clinical trials have repeatedly shown mood benefit from exercise in adults with clinical depression

I exercise as one form to fight depression and it helps a lot, doing something many would consider an extreme sport. If I'm not out there pushing limits every 2-3 days I notice how my mind get's caught up in little stuff.

But once you get injured the hole you fall into is really really deep. There has to be another way.

Spoken like an exemplar of n=1 'I understand it' individual who experienced mild depression and thinks they know everything there is to know, while being completely ignorant of chronic treatment resistant depression which is the real issue.

Exercise, sleep, mindfulness, SSRI, whatever other things might work for you, they don't work for everyone. Don't mistake your experience for describing 100% of the population.

Exercise specifically is a non-solution and has been demonstrated to be a step on the hedonic treadmill. Once fitness goals are achieved, the depression benefit wears off unless ones sets every more difficult fitness goals. No different than reaching for that pay rise, that better car, that bigger house, etc. It's never a solution.

Sleeping, eating, and working out only do so much and are very difficult to do when one is already fighting depression. You simply cannot tell everyone "just do these 3 easy things" and expect that to work or for people to even listen. While those are critical for people, especially the depressed, it truly mocks the struggle and ignores the underlying issue.

Far more important is the issue of work or school utterly dominating our lives, leaving little time to deal with the other stresses in life and even less time to decompress or socialize. Only a massive societal effort to reduce these stresses will make an substantial reduction in these widespread mental struggles.

I’m skeptical, though I must admit that I’m not a subject matter expert.

The disruption of serotonergic pathways probably isn’t something that can be amended by a serotonergic therapy. I’d actually predict that individuals with Alzheimer’s would experience a diminished effect when taking LSD.

My bias here is more broad. I’m of the belief that the cure to Alzheimer’s is more likely biological than it is chemical. Not overlooking the interoperability of these two things, but rather suggesting that it’s probably a problem that requires a more sophisticated treatment than purely consuming a drug.

That said, I’m very excited to see microdosing being studied and interested in the outcomes of this trial, whatever they may be. Certainly, the results here could tell us something we haven’t yet discovered about LSD or Alzheimer’s, even if there is no therapeutic application in this case.

With regard to treatment, what are you basing your belief on? Plenty of diseases can be halted or cured with chemicals.

The numerous trials with "chemicals" that had absolutely no effect on Alzheimer so far. It is not for lack of trying at this stage.

Of the research I’ve read, many scientists suggest that it’s the accumulation of plaques that cause Alzheimer’s.[0]

There’s uncertainty as to what protein is responsible for the degenerative effects.[1]

My bias exists for the fact that I believe the cure to Alzheimer’s is removing or preventing the development of this plaque. At least I’ve been lead to believe this is among the most promising cures.[2] Amyloid protein is particularly tricky because it’s insoluble. I don’t think we could develop a purely chemical solution for the fact that it would likely be destructive to our own biology. And I think both gene expression and enzyme production are unlikely to be able to changed with just a drug.

[0] https://www.sciencedaily.com/releases/2018/03/180326161000.h...

[1] https://www.sciencemag.org/news/2016/05/tau-protein-not-amyl...

[2] https://rupress.org/jem/article/215/3/927/42616/BACE1-deleti...

The beta amyloid theory is pretty tired at this point since the correlation between plaques and Alzheimer's is only moderate.

Imo Alzheimer's is probably more related to the brain falling into dysdunctional, self reinforcing patterns of synaptic connectivity.

Neural plaques might exacerbate this problem by disrupting connectivity, but clearly the brains of many people with plaques learn to route around this damage to retain functionality.

> self reinforcing patterns of synaptic connectivity

Any sources for this? I’d be very interested to read the literature on this.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207354/

Just a jumping off point review on the weakness of the amyloid theory.

The connectome dysregulation theory is my own, it hasn't appeared in the scientific literature as of yet due to our inability to perform fine mapping of synaptic connections without microtoming a cadaver brain.

That's a cool theory. The brain tries pretty hard to maintain criticality (hard as in, disruptions cause it to return to that setpoint quickly). It's possible that inability to recover or maintain optimal processing criticality can lead to corruption of the connectome.

https://www.sciencedaily.com/releases/2019/10/191007113314.h...

See this case of a Colombian woman whose brain is full of the amyloid plaque but she is demntia free due to a genetic mutation

https://www.sciencemag.org/news/2019/11/colombian-woman-s-ge...

the study demonstrsted safety, not effectiveness; which is ironic, because the safety of lsd is well established, while the effectiveness of anything to treat alzheimers is not.

Disappointing to see some of the comments. I'm thinking a number of posters here haven't tried hallucinogens...

I have a good friend who tried mushrooms for the first time. He went completely psychotic. We had to call police/emt to subdue him. Ended up tied down to a gurney until he sobered up in the hospital for a couple hours.

Psychedelic are NOT for everyone. It is dangerous to suggest they are.

I can't imagine the police helping in that situation at all.

One time this 'guru' told me, "That is what happens when you try to put a 6 cylinder drug into a 4 cylinder mind." when referring to someone at a festival who lost their shit.

Granted it could have been a bad dose, but when everyone else around them was fine, it typically is the user who was not ready for the experience or had some underlying issues they were not dealing with, and when you take these types of drugs you don't have a choice but to deal with it.

Sadly the police/emt way of dealing with it probably caused more trauma than anything but I understand their reasoning in doing what they did.

When someone is trying these types of substances for the first time it is a good idea to make sure they are in a good frame of mind, have a few people guiding them on their journey.

If you decide to randomly take mushrooms for the first time in an environment where not everyone is on the same level as you and you have no one to guide you through your journey, you are going to have a bad time.

I like that 'guru' quote. When it comes to the trip. I always hear about the 'have a sober friend, or a trip buddy, etc' I've never thought this was the best idea. I think it could be worse for someone in a bad state to have to deal with other people.

Let a person be by themselves. Chances are they will just sit there and go through the corridors of their mind. There may be sheer terror, and at some point there will hopefully (likely) be peace and euphoria. If nothing else it will wear off in a handful of hours and if they were just sitting by themselves then they can hopefully shake it off and get on with things. I think it's dealing with other people that could raise the situation to unstable levels.

and a story about a YouTube engineer who took LSD over the summer and freaked out and nearly killed/ran over a bunch of people https://www.buzzfeednews.com/article/davidmack/youtube-engin...

If you think that's crazy check out this drug that caused almost 11,000 vehicle deaths last year:

https://www.nhtsa.gov/risky-driving/drunk-driving

And it's still legal!!!

you can still make decisions while under influence of alcohol. With LSD you lose “control” with a full dose, so bad trips can make people highly unpredictable in ways that isn’t true about alcohol. That’s my point.

Alcohol can make people highly unpredictable and violent.

Sure most people with a few drinks are fairly predictable (although their reaction times drop quickly). But many people get blackout drunk all the time, and that leads to incredibly erratic behavior.

Have you ever used alcohol or seen the affects it causes on others? I'm not advocating for or against either drug but this is a most unusual opinion, it sounds like you are describing alcohol to a tee in some gaslighting way.

Have you ever actually taken LSD? I’m pretty sure many people have lost complete control of their judgement and rational mind drinking alcohol in their college days... or any age, really. I would never suggest driving or anything dangerous on LSD, but I was still able to tell myself “ok, this is real, that’s not real” when I took LSD.

The most surprising thing from my (single) LSD experience was it somehow changed my perspective at the time on work and school. Almost overnight, I went from being apathetic and unmotivated to seeing work as the most moral thing one could do, and something to be proud of. I’m not sure why since I don’t remember any conversations about work at the time. It felt like a lightbulb.

It's very clear you have not taken it before, and seem to be (possibly willfully) ignorant about alcohol.

LSD is not a dissociative like GHB or PCP.

Almost everyone on a full dose will be completely lucid with full mental clarity. Of course there are outliers and mega doses, but those are not the norm. I would argue a common side effect is INCREASED awareness, not loss of control.

Alcohol on the other hand...

I've never "lost control" with LSD or seen anyone do the same. Typically it is like a magic eye book where you can dial yourself back to reality.

DMT on the other hand, when someone blasts off they are gone for a good 10-15 minutes.

"You can still make decisions while under influence of alcohol"

...Sure, such as deciding to drive home despite the fact you are barely able to walk to your car.

Pollan, in the book, repeatedly stressed the importance of taking psychedelics in the presence of sober professionals. This is because a “bad trip” can not only be dangerous to the people around the user, but also very traumatic for the user.

If the LSD was taken in a medical environment the user would absolutely not have be allowed to drive. The user would not have be given an additional dose while delusional. When trying to leave the user would most likely have been calmed by a specialist. If this failed the treatment would be conducted in a secure facility and have effective procedures for physically restraining the individual.

There’s also a huge pharmaceutical difference between 4 doses of street acid and micro dosing pharmaceutical grade LSD.

That article says he took "two doses", which could mean just about anything but likely means at least 200-400ug, or at least 8 to 60 times the doses in the microdosing trial. The highest dose in the trial was where users just started to feel any drug effects at all.

In alcohol terms, they're studying the effects/safety of a fraction of a beer whereas that guy chugged a case of beer.

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