Why we don’t seem to change -- and how a strange drug made me rethink it

Alexanderr

Alexanderr

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I've got this very nice quote in one of my personal documents:

The "self" is not a static noun. It is the cumulative, emergent property of its own actions. You are the sum of your "dos.”

Yes, it makes for a good quote on a wall, but here's why its closer to biological reality than you might think.

look-in-the-mirror-presence.gif


Who are you? No, who are you really? Are you just your name, birthplace or social security number? No? Maybe you define yourself in relation to others. You're someone's brother, a son, a friend or partner (lol no).

See, I adopt a different worldview. As I see it, you are those policies your system executes by default. In simpler words, you are that which you do, on average.

This change of framing is important. Most people identify themselves by their nouns, "I'm a cook, I'm a software developer, I'm a dad or I'm a gamer, etc", this measures you by the verbs. "I cook, I do software developing, I raise my children or I play videogames".

This is important because it's much closer aligned to how our biology actually operates. There's no way (mechanistically) for your brain to run on a label, it runs on encoded actions given certain triggers.


535d7d39d6b57a922a67d85f135272fd.gif


For example, you come back from school, you're bored (trigger), the system defaults to "pick up phone, scroll social media" (action), until you realize you still gotta make your homework (termination). Or, you feel hungry (trigger), so your system defaults to "check the fridge" (action), until you've eaten and feel satisfied (termination).

These moves are encoded in your synapses, a network of connected neurons, with a particular pattern firing whenever you're doing anything.

All of your habits, ALL of them, are merely the sum of action bundles you've learnt to take given some context.

The wider implication here is: Action comes first. The “self” is what remains once those actions repeat.

Consequently, any and all advice given without a concrete set of actions to take, given a certain situation might as well be useless.

1766303591145

This flips the usual teaching model on its head


Most instruction tries to do this:
Teach the principle -> hope the actions follow

But the real path is:
Enact the actions -> notice they work -> stance crystallizes

Okay, but why should I care, @Alexanderr?

Because until you embody this truth, you’ll keep mistaking understanding for change -- and wonder why nothing sticks.

But I reckon this isn't news to a lot of you. You know. You know your habits define who you are, but you cannot seem to change them. You feel trapped by the parts of you that won't listen to reason. Like a ball endlessly trying to roll up a hill but mercilessly brought down by gravity.
1*zwRxp8muf36qu5lqi6ZDVA.gif

See, I didn’t set out to write this as a drug thread. I set out to understand why change keeps undoing itself.

May I here introduce you to,

CREBINOSTAT

1766300842782


So, you think I'm introducing you to a miracle drug? I'm not. But here's why it's interesting anyway:

See, the problem for most people is that they can change any one of their moves any given day, the problem is that they don't stick. You go to the gym one day, but the action doesn't stick. You eat healthy one day, but the practice doesn't stick. Why is this?

Because evolution never wanted the (adult) human brain to be one that deviates from a stable state easily. It prioritized changing easily and changing quickly in early youth, but being efficient and stable nearing or upon adulthood. Meaning, if your current state is just enough to survive and reproduce, it's a-okay to evolution.

The implications here being that for you to change, meaningfully, you need to, (using our ball stuck on a U-shaped curve analogy) either:

1. Add massive energy
Trauma, ecstasy, crisis, obsession
-> brute-force shove over the ridge

2. Sustain repeated pushes
Slow learning, repetition, scaffolding
-> gradually reshape the basin

3. Change the landscape itself
Alter plasticity, consolidation, or stability parameters
-> same push now travels farther

Most adult change fails because people try #1 briefly or #2 inconsistently, while the system is actively defending #0: stability.

#3 is where Crebinostat comes in.

Crebinostat does not give the ball more force.
It does not create new hills.

It subtly:
  • flattens the curvature
  • widens the basin
  • lowers the ridge height between basins
So a displacement that would normally roll back…now survives long enough to be turned into structure.

How? By lowering the bar for you brain to encode a memory, and thus not forget it.

What people don't understand about our biology and learning is that, forgetting is just as big a part. Your brain forgets all types of irrelevant noise (ex. random license plates) so you can learn or remember what matters (ex. mom's name).

Under normal conditions, the brain only locks in experiences that are clearly tagged as important; usually through strong emotion, novelty, fear, or consequence.

1766302961870

The problem is that there’s no immediate way for the brain to tell what will matter long-term. Your brain doesn’t know that skipping Chipotle is actually good for you.

All it records is a deviation from usual, considers it a fluke, prunes it during sleep, and moves on. Result? The memory trace "skip Chipotle" is never encoded (long term).

The claim here isn’t that one exposure creates a habit, but that a correct action is far less likely to be pruned by the brain -- so you’re not always starting again from square one.

Crebinostat enhances memory by jointly lowering transcriptional thresholds (via potent inhibition of HDAC1/2/3) and stabilizing newly potentiated synapses during the early consolidation window (via potent inhibition of HDAC6), allowing weaker or shorter learning experiences to survive long enough for systems-level consolidation.
1766301849175
1766302010384
1766301940122

The exact division of labor between transcriptional gating (HDAC1–3) and cytoskeletal/synaptic stabilization (HDAC6) is still being worked out, but both converge on the same outcome: fewer new traces fall below the survival threshold.

I'll make a more expansive thread dissecting the research later.

The failure mode for most people isn't in taking a different action, it's in not forgetting it immediately after. This is why Crebinostat is revolutionary.

As an example, there was a research study done. Researchers had a mice setup that was designed to test whether a weak learning experience could be converted into a durable long-term memory if the brain’s consolidation (remembrance) machinery was biased in its favor.
1766299295164


Task: A mouse briefly explores two identical objects, and 24 hours later memory is inferred if it preferentially explores a newly introduced object over the familiar one.

Key idea: They used learning examples (identical objects) that were deliberately too weak to produce long-term memory on their own.

Normally:
  • the mouse experiences something once or briefly
  • it learns it in the moment
  • but forgets it by the next day
Basically, the experiment asks:
Can a drug make that same weak experience stick?

The answer: A resounding yes -- Crebinostat reliably turned a weak, normally forgettable object-recognition experience into a robust long-term memory.

Fass DM et al. Crebinostat: A novel cognitive enhancer that regulates chromatin-mediated neuroplasticity and enhances memory. Neuropharmacology (2013).

BUT @Alexanderr THAT'S IN MICE!!! WHERE ARE THE HUMAN TRIALS? HUH!? HOW'D WE KNOW IT WOULD TRANSFER?
Fairs, but without me going into the science of it all, given what we know about mice and humans... If Crebinostat failed to transfer at all, that would actually be more surprising than a modest, domain-limited benefit showing up in humans.

If I had to answer in one sentence, vividly, what sets Crebinostat apart from all other obscure or grey market drugs I've come across, it's that:

Crebinostat doesn’t push you to learn harder or feel more; it strengthens the brain’s internal scaffolding so that whatever you already did has a much higher chance of not collapsing overnight.

This is extremely rare because most drugs act on moment-to-moment signaling or arousal, whereas Crebinostat targets the slow, normally inaccessible molecular gate that decides whether learning is kept or discarded after the fact.

meet-up-maca.gif

Examples of every day tasks people's brain generally forgets to store:
  1. Learning someone’s name once and actually remembering it the next day.
  2. Having a single good practice session stick instead of feeling lost again tomorrow.
  3. Adopting a simple habit or rule of thumb and finding yourself using it later without effort.
These are universal, frustrating failures of memory we've all experienced -- and exactly the kind crebinostat seems built to fix. Of course, power goes both ways. It amplifies whatever you practice, not what you intend.

But why @Alexanderr, why do you post about an obscure, non-human tested research drug that would be inaccesible anyway?

Because for the first time (as far as I know) it's available to the general public. Although trough some peculiar means. I'll explain.

Someone I consider a friend is hosting a group buy for the drug, it's open until 31st of December. I make no money off of it, but I've been waiting for this opportunity to come by a couple years now [ever since I tried Vorinostat (similar, but less effective for these purposes)].

So I'd feel bad if those of you who are as interested as me in this entire bio-hacking stuff miss out on this (maybe once in a lifetime, idk) opportunity.

You can read and find more here.

Merry Christmas, fellas, I'll keep you updated on this pet project of mine.
Christmas Eve Running GIF by MOODMAN


THIS THREAD ISNT FOR IQCELS :lul::lul::lul:
 
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tl:dr what does it do?
 
seems like a great read
 
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holy shit mirin high effort thread
 
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A substance I've never heard of?

1766304867951


HDAC inhibition sounds pretty interesting. I haven't looked into it but I will definitely do that this week, bookmarked.
My grandmother had Alzheimer's and I'm pretty interested in anything that could prevent this for my parents in the next couple decades.
Thinking of it, I wonder if there's interest in more research on a compound like this.

I'll have to read more on it, but I read everything here and it piqued my interest, really nice thread.
 
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read everything good read
 
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Being able to do something that you don’t want to do/don’t feel like doing is one of the most admirable things that a human can do. You’re quite literally breaking from the loop that won’t let you succeed.

A lot of people know what needs to be done, yet they can’t do it because they don’t have the willpower to actually do it.

Also nice thread, how long did it take you to write this?
 
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HDAC inhibition sounds pretty interesting. I haven't looked into it but I will definitely do that this week, bookmarked.
It's very interesting, that's what got me hooked. Crebinostat and vorinostat don’t act like most drugs that tweak ongoing neural activity (firing rates, receptor tone, neuromodulators).
They act upstream of that, at the level that decides what future neural activity is even possible. That puts them much closer to developmental biology than to classical psychopharmacology.
 
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Being able to do something that you don’t want to do/don’t feel like doing is one of the most admirable things that a human can do. You’re quite literally breaking from the loop that won’t let you succeed.

A lot of people know what needs to be done, yet they can’t do it because they don’t have the willpower to actually do it.

Also nice thread, how long did it take you to write this?
It's consistency, it's doing the thing again and again. I'm sure we've all behaved different, transiently (for a moment, or day), it just didn't stick. We reverted back to our old selves the day after. Crebinostat changes that.

All around might've taken me about ~2h I think, but I've thought about it a lot the past week so
 
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good thread :feelswhy:
 
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You haven’t mentioned the price! After all, 99% of life’s shitness comes from poverty anyway.
 
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Very interesting thread as always :feelshmm:
 
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You haven’t mentioned the price! After all, 99% of life’s shitness comes from poverty anyway.
Group buy, so 74 euros per gram. Any one particular session might be 5-10mg, so that's 100-200x uses, approximately. With that said, this is not a drug to be used lightly.

As I alluded to earlier, your brain is an amoral engraver. If you take this drug and proceed to scroll TikTok for an hour, you've just supercharged a memory trace that was probably already well engraved (making it even harder to quit).

Power goes both ways, and so I don't recommend this drug to anyone that isn't serious enough to do a little reading and treat it like surgical intervention.

I myself won't take it hastily for this very same reason. Not because of safety concerns but because its very mechanism necessitates it.
 
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Seems pretty cool
 
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It's very interesting, that's what got me hooked. Crebinostat and vorinostat don’t act like most drugs that tweak ongoing neural activity (firing rates, receptor tone, neuromodulators).
They act upstream of that, at the level that decides what future neural activity is even possible. That puts them much closer to developmental biology than to classical psychopharmacology.
Yeah the upstream idea makes sense, sounds like it would encourage the brain to "save changes" if that makes sense.

That's kinda what made me get some interest in GB-115 since it doesn't hit GABA directly but is rather CCK-related. (offtopic: I'm looking into it because I'm looking for ways to make a benzodiazepine taper easier). Completely different mechanism than Crebinostat, but a similar appeal as in not forcing something but making it easier for a change to stick which is what it reminded me of!

Correct me if I'm wrong, but since Crebinostat amplifies what you practice, how would someone avoid reinforcing wrong habits like bad routines, or stuff like doomscrolling, etc?
 
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Yeah the upstream idea makes sense, sounds like it would encourage the brain to "save changes" if that makes sense.
Yes, basically. We change all the time, the problem is that when you're an adult, or near to it, stability is the default, with change being a feature. So your brain sees actions that deviate from your normal as noise, and wipes them. Unless you reinforce them relentlessly.

During sleep your brain 'replays' your entire day, but only those memory traces (experiences) that were 'tagged', and robust enough to last until sleep get replayed preferentially. Trough this replay mechanism (and others) these experiences gradually become a part of you. Those that weren't get pruned.

Like learning how to drive a car, first day everything's foreign to you, everything requires your utmost concentration. But as the days (or nights) go by, you learn (automatize) a lot of the things that kept you occupied initially. Importantly, your brain also learned what didn't matter to drive--this is what I mean when I say forgetting is integral to learning.

Correct me if I'm wrong, but since Crebinostat amplifies what you practice, how would someone avoid reinforcing wrong habits like bad routines, or stuff like doomscrolling, etc?
This is the beauty of Crebinostat. It doesn’t make everything stick-- only what is actively being executed. Only those synapses actively being used for something (say to watch TV, read a book, or play football) more likely to survive the night, such that they can become more automatized (trough systems consolidation).

So, the solutions' to avoid doing those things during the ~90min window that its active. (The drug acts during a short waking window, but its effects are expressed later, during sleep-dependent consolidation.)

See, plasticity and memory consolidation are very powerful levers that evolution consciously decided to to tune down in adulthood. Imagine being a 25 year old hunter gatherer, and suddenly (permanently) re-gaining some childlike irrational fear because of some bad experience on a hunt.

Generally, your brain treats one-off experiences as noise, and prunes them. Good or bad. Evolution made the bet it's more beneficial to be adaptable early, and stable and efficient later-- when it comes to survival & reproduction.

For us modern day humans, survival is the default, so this scheme bites us in the ass more often than we'd like.

So the real risk isn’t accidental reinforcement; it’s negligence. Its a tool that records what you do, not what you intend.
Treat it casually, and it will faithfully encode that too.
 
Mirin the effort and quality

Im now gonna do drugs
 
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What did you take to write such walls of text?
 
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I've got this very nice quote in one of my personal documents:

The "self" is not a static noun. It is the cumulative, emergent property of its own actions. You are the sum of your "dos.”

Yes, it makes for a good quote on a wall, but here's why its closer to biological reality than you might think.

look-in-the-mirror-presence.gif


Who are you? No, who are you really? Are you just your name, birthplace or social security number? No? Maybe you define yourself in relation to others. You're someone's brother, a son, a friend or partner (lol no).

See, I adopt a different worldview. As I see it, you are those policies your system executes by default. In simpler words, you are that which you do, on average.

This change of framing is important. Most people identify themselves by their nouns, "I'm a cook, I'm a software developer, I'm a dad or I'm a gamer, etc", this measures you by the verbs. "I cook, I do software developing, I raise my children or I play videogames".

This is important because it's much closer aligned to how our biology actually operates. There's no way (mechanistically) for your brain to run on a label, it runs on encoded actions given certain triggers.


535d7d39d6b57a922a67d85f135272fd.gif


For example, you come back from school, you're bored (trigger), the system defaults to "pick up phone, scroll social media" (action), until you realize you still gotta make your homework (termination). Or, you feel hungry (trigger), so your system defaults to "check the fridge" (action), until you've eaten and feel satisfied (termination).

These moves are encoded in your synapses, a network of connected neurons, with a particular pattern firing whenever you're doing anything.

All of your habits, ALL of them, are merely the sum of action bundles you've learnt to take given some context.

The wider implication here is: Action comes first. The “self” is what remains once those actions repeat.

Consequently, any and all advice given without a concrete set of actions to take, given a certain situation might as well be useless.

View attachment 4445555
This flips the usual teaching model on its head


Most instruction tries to do this:


But the real path is:


Okay, but why should I care, @Alexanderr?

Because until you embody this truth, you’ll keep mistaking understanding for change -- and wonder why nothing sticks.

But I reckon this isn't news to a lot of you. You know. You know your habits define who you are, but you cannot seem to change them. You feel trapped by the parts of you that won't listen to reason. Like a ball endlessly trying to roll up a hill but mercilessly brought down by gravity.
1*zwRxp8muf36qu5lqi6ZDVA.gif

See, I didn’t set out to write this as a drug thread. I set out to understand why change keeps undoing itself.

May I here introduce you to,

CREBINOSTAT

View attachment 4445463

So, you think I'm introducing you to a miracle drug? I'm not. But here's why it's interesting anyway:

See, the problem for most people is that they can change any one of their moves any given day, the problem is that they don't stick. You go to the gym one day, but the action doesn't stick. You eat healthy one day, but the practice doesn't stick. Why is this?

Because evolution never wanted the (adult) human brain to be one that deviates from a stable state easily. It prioritized changing easily and changing quickly in early youth, but being efficient and stable nearing or upon adulthood. Meaning, if your current state is just enough to survive and reproduce, it's a-okay to evolution.

The implications here being that for you to change, meaningfully, you need to, (using our ball stuck on a U-shaped curve analogy) either:

1. Add massive energy
Trauma, ecstasy, crisis, obsession
-> brute-force shove over the ridge

2. Sustain repeated pushes
Slow learning, repetition, scaffolding
-> gradually reshape the basin

3. Change the landscape itself
Alter plasticity, consolidation, or stability parameters
-> same push now travels farther

Most adult change fails because people try #1 briefly or #2 inconsistently, while the system is actively defending #0: stability.

#3 is where Crebinostat comes in.

Crebinostat does not give the ball more force.
It does not create new hills.

It subtly:
  • flattens the curvature
  • widens the basin
  • lowers the ridge height between basins
So a displacement that would normally roll back…now survives long enough to be turned into structure.

How? By lowering the bar for you brain to encode a memory, and thus not forget it.

What people don't understand about our biology and learning is that, forgetting is just as big a part. Your brain forgets all types of irrelevant noise (ex. random license plates) so you can learn or remember what matters (ex. mom's name).

Under normal conditions, the brain only locks in experiences that are clearly tagged as important; usually through strong emotion, novelty, fear, or consequence.

View attachment 4445546
The problem is that there’s no immediate way for the brain to tell what will matter long-term. Your brain doesn’t know that skipping Chipotle is actually good for you.

All it records is a deviation from usual, considers it a fluke, prunes it during sleep, and moves on. Result? The memory trace "skip Chipotle" is never encoded (long term).

The claim here isn’t that one exposure creates a habit, but that a correct action is far less likely to be pruned by the brain -- so you’re not always starting again from square one.

Crebinostat enhances memory by jointly lowering transcriptional thresholds (via potent inhibition of HDAC1/2/3) and stabilizing newly potentiated synapses during the early consolidation window (via potent inhibition of HDAC6), allowing weaker or shorter learning experiences to survive long enough for systems-level consolidation.
View attachment 4445485View attachment 4445497View attachment 4445494
The exact division of labor between transcriptional gating (HDAC1–3) and cytoskeletal/synaptic stabilization (HDAC6) is still being worked out, but both converge on the same outcome: fewer new traces fall below the survival threshold.

I'll make a more expansive thread dissecting the research later.

The failure mode for most people isn't in taking a different action, it's in not forgetting it immediately after. This is why Crebinostat is revolutionary.

As an example, there was a research study done. Researchers had a mice setup that was designed to test whether a weak learning experience could be converted into a durable long-term memory if the brain’s consolidation (remembrance) machinery was biased in its favor.
View attachment 4445413

Task: A mouse briefly explores two identical objects, and 24 hours later memory is inferred if it preferentially explores a newly introduced object over the familiar one.

Key idea: They used learning examples (identical objects) that were deliberately too weak to produce long-term memory on their own.

Normally:
  • the mouse experiences something once or briefly
  • it learns it in the moment
  • but forgets it by the next day
Basically, the experiment asks:


The answer: A resounding yes -- Crebinostat reliably turned a weak, normally forgettable object-recognition experience into a robust long-term memory.



BUT @Alexanderr THAT'S IN MICE!!! WHERE ARE THE HUMAN TRIALS? HUH!? HOW'D WE KNOW IT WOULD TRANSFER?
Fairs, but without me going into the science of it all, given what we know about mice and humans... If Crebinostat failed to transfer at all, that would actually be more surprising than a modest, domain-limited benefit showing up in humans.

If I had to answer in one sentence, vividly, what sets Crebinostat apart from all other obscure or grey market drugs I've come across, it's that:

Crebinostat doesn’t push you to learn harder or feel more; it strengthens the brain’s internal scaffolding so that whatever you already did has a much higher chance of not collapsing overnight.

This is extremely rare because most drugs act on moment-to-moment signaling or arousal, whereas Crebinostat targets the slow, normally inaccessible molecular gate that decides whether learning is kept or discarded after the fact.

meet-up-maca.gif

Examples of every day tasks people's brain generally forgets to store:
  1. Learning someone’s name once and actually remembering it the next day.
  2. Having a single good practice session stick instead of feeling lost again tomorrow.
  3. Adopting a simple habit or rule of thumb and finding yourself using it later without effort.
These are universal, frustrating failures of memory we've all experienced -- and exactly the kind crebinostat seems built to fix. Of course, power goes both ways. It amplifies whatever you practice, not what you intend.

But why @Alexanderr, why do you post about an obscure, non-human tested research drug that would be inaccesible anyway?

Because for the first time (as far as I know) it's available to the general public. Although trough some peculiar means. I'll explain.

Someone I consider a friend is hosting a group buy for the drug, it's open until 31st of December. I make no money off of it, but I've been waiting for this opportunity to come by a couple years now [ever since I tried Vorinostat (similar, but less effective for these purposes)].

So I'd feel bad if those of you who are as interested as me in this entire bio-hacking stuff miss out on this (maybe once in a lifetime, idk) opportunity.

You can read and find more here.

Merry Christmas, fellas, I'll keep you updated on this pet project of mine.
Christmas Eve Running GIF by MOODMAN


THIS THREAD ISNT FOR IQCELS :lul::lul::lul:
Good thread

Btw do I have your permission to make you a Q&A?
 
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Btw at what dosage and for how long did you use it?
 
So it's a more potent vorinostat? That's what they seem to be saying on reddit, I think I need help more so with fear extinction and anxiety before building habits so I'd value fear extinction more. My vorinostat got seized last time but maybe I will try again with this as I'm quite desperate. I am in a cycle of rotting in bed doing nothing that is very difficult to break
 
I guess I haven't explained for what practices I'll be taking it exactly. It's a few. I play two instruments, and crebinostat trough its mechanism is particularly well suited to improve my practice efficiency.

For those who play the piano, or any instrument for that matter, you all know the feeling of having practiced some hard passage for maybe for 15-30 mins., getting lazy (so not repeating it the following day) and it's turned sloppy 2-3 days later. 2-3 weeks? Forget it; it's gone.

You don't start where you left off.
1766314748436


Honestly anyone familiar with the forgetting curve (trough studying, for instance) knows. This is why people tell you to practice daily. That which you practiced yesterday is still available, in high fidelity, for a short window- and that's assuming you practiced long enough with focus the day before so your brain actually 'got it'.

Since Crebinostat can turn what would otherwise be a weak memory trace into a long-form, robust memory trace (which doesn't fade in a few days) your practice becomes a lot more efficient.

But this isn't linear, it's exponential, you start your subsequent sessions with a much higher baseline, and consequently learn more.

Okay, but this might be the most unimaginative execution of Crebinostats' capabilities.

The real leverage isn’t motor memory -- it’s procedural cognition.
The moves you reach for when you’re confused.
What I'm really after would have a much, much higher ROI.

That is changing my intellectual habits. If you're not a nerd, or someone who otherwise cares about academics or job prosperity -- you won't understand.

But to put it into context for the rest of youse... Elite thinkers, prodigious talents, genius -- what sets them apart?

A lot of people would say innate talent, they were born that way, they were just gifted genetically. I disagree.
1766319149812


See, the more that I learn about learning science, cognitive neuroscience, developmental biology, neuropharmacology and the actual practices of elite thinkers themselves the more I converge on this:

Elite thinkers are merely those of us who, at an early age, discovered a set of cognitive heuristics, that work particularly well in their domain, and relentlessly applied them because of it. This early advantage then compounds huge gap between them and their agemates, at which point us observers look at the kid and say "he's just gifted".

In physics (my domain, but applicable elsewhere too) this could be anything from:
* restating the problem when confused
* removing a variable and see how that changes things
* playing with extremes
* drawing a diagram

None of these are impressive in isolation.
What matters is that, for elite thinkers, these moves fire without deliberation.
They’re not choices; they’re defaults.

They've found a scalable strategy for exploring the search space of their domain-specific problems much quicker. Domain-specific is doing the heavy lifting here. You'll find even the top geniuses in one field are just as bad as you and me at something different. A great mathematician might sucks at understanding systems in biology, or a gifted musician unable be chemical equation to save their life.

We’re usually not missing intelligence, we’re missing automaticity at the right decision points.

TLDR: Basically I'm set out to change my cognitive habits, and if I succeed, this should pay dividends into perpetuity. This is more than just trying to become an A-student.

There's a few other pursuits, I'm learning French, for example, it'll come in handy there. Here's a more elaborate thread where I speak about vorinostat (similar, but less effective).

Of course, I don’t know if this will work.
But if it does, it wouldn’t just make me better at learning -- it would change what my brain reaches for by default.
And that’s a permanent return.
 
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Btw at what dosage and for how long did you use it?
5-10mg, 5mg initially, I'll scale up until I find a minimum effective dosage and then stop. It's a lot more potent than vorinostat (which I take 50-100mg of). I haven't taken crebinostat yet, I'll get it early January.
 
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So it's a more potent vorinostat? That's what they seem to be saying on reddit, I think I need help more so with fear extinction and anxiety before building habits so I'd value fear extinction more. My vorinostat got seized last time but maybe I will try again with this as I'm quite desperate. I am in a cycle of rotting in bed doing nothing that is very difficult to break
No, there are a few key differences that matter, and for fear extinction specifically, vorinostat might actually be the better tool.

Crebinostat is more selective than vorinostat. Vorinostat hits HDACs more broadly (which is why it’s FDA-approved for cancer), and in my experience that global action can come with fogginess or fatigue, though it does work well for fear extinction.

Where Crebinostat differs is how it biases learning. It doesn’t just “turn plasticity up.” It lowers the threshold for consolidation specifically in circuits that were active, making weaker or more ordinary learning events more likely to survive overnight.

In practical terms: vorinostat opens the gate, but still relies heavily on strong emotional tagging. Crebinostat both opens the gate and makes it easier for a signal to count as worth keeping.

So mundane but correct experiences (not just dramatic ones) have a higher chance of sticking.

That’s why I think of Crebinostat as both a key and a volume knob, whereas vorinostat is mostly a key.
 
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