self_made_human
C'est la vie
I'm a transhumanist doctor. In a better world, I wouldn't need to add that as a qualifier to plain old "doctor". It would be taken as granted for someone in the profession of saving lives.
At any rate, I intend to live forever or die trying. See you at Heat Death!
Friends:
I tried stuffing my friends into this textbox and it really didn't work out.
User ID: 454
self_made_human
C'est la vie
4d ago
The post went too far, even for LessWrong's open-minded standards. The comments there are 90% people tearing into it.
self_made_human
C'est la vie
5d ago
Thank you!
self_made_human
C'est la vie
5d ago
Ketamine vs LSD/psilocybin are very different in terms of pharmacology, even if the net effect on depression is the same. The former acts by modulating NMDA primarily, the latter 5HT2A.
Subjectively, a k-hole is light years apart from psychedelics.
They then tend to increase neuronal plasticity, via different mechanisms of action.
Its weird that we found three recreational drugs from different families doing this, and no non-recreational ones.
Well, ECT and transcranial magnetic stimulation use no drugs at all (barring incidental anesthesia and muscle relaxant in the former). They also, after a few sessions, relieve depression for months or years. Once again, the terminal effect is believed to be increased synaptogenesis/plasticity. ECT has been around for 70 years.
There's nothing particularly weird about it. The regulatory environment just became somewhat more friendly towards exploring less conventional therapies when the anecdotal evidence became strong enough.
Personally, I couldn't care less how "weird" this seems in the first place, as long as the treatments work. The human body is weird and unintuitive in the first place.
self_made_human
C'est la vie
5d ago
I shared my latest post on the Slate Star Codex subreddit, and Scott showed up in the comments to complain about how I'd characterised him in the article. I dutifully apologised and rephrased the offending passage. In the list of things that made me feel ashamed of myself this year, this was in the top five.
My condolences. If that happened to me, I'd be driven to drink.
Kind of like a less overtly titillating Aella, and, in my view, far more physically attractive.
(Presumedly) white men really not beating the allegations!
(She is pretty, but I found this particular photo profoundly disturbing. To be fair, now that I actually opened it, it's AI generated on purpose)
self_made_human
C'est la vie
6d ago
Funnily enough, I have a comment saying pretty much the same thing, but that was over a year back. We can only hope that Scott hasn't forgotten his estranged children over here. He's still got his account, though it's been inactive for a while, at the very least he's aware of our existence.
self_made_human
C'est la vie
6d ago
And very few of them are tempting to use in such ways. Those substances doctors have in fact used in harmful ways. The US just recently had a dustup about opioids.
I bear no responsibility for any that, but leaving that aside, there's an opioid epidemic. If there's a Magic Mushroom epidemic, it must be endemic to Burning Man.
It doesnt explain why no non-recreational drugs do the same.
That's dead wrong. There are all kinds of drugs that have ~nil recreational value, but which engender physiological or psychological dependence.
A non-exhaustive list would include SNRIs, clonidine, gabapentin and pregabalin, corticosteroids, laxatives, nasal decongestants.
These are all substances that the body, once accustomed to, complains quite loudly and painfully about letting go of.
self_made_human
C'est la vie
6d ago
Substack has a feature where the creator can view the original sources of any traffic to a particular blog.
So far, it was mostly a curiosity, I was used to seeing Reddit, or "Email", those being places where I'd personally shared my writing. I'm not sure what links posted on The Motte show up as, but presumably "Direct" since I strip out the usual tracking IDs out of courtesy.
My latest post did numbers, at least by baby Substack standards. I'd seen a decent amount of traffic from X, and the site's abysmal search did find someone of decent repute shouting it out. A few large Substack authors reblogged it to boot. Someone big even wants to interview me, though my desire for online pseudonymity might make that a no-go.
But then, when I checked back later today, I was immensely surprised to see Gwern in the list. I mean, he's a big name, but surely he doesn't have an independent listing? I dug in, and to my immense pride, I saw that my post had been deemed worthy of ending up as a link he'd rounded up on his personal site.
I'm very chuffed, but I find myself chagrined by the fact that the number of people I know IRL I can boast about this to round up to zero. The only way I could be more pleased is if it caught Scott's eye, but I've managed to achieve that once before so it's off the bucket list.
Motherfucking Gwern-senpai noticed me. I knew that obsessively tracking down links and literature reviews as well as digging into neurophysiology would pay off. Now I feel awful about not adding a dozen footnotes and citations :(
Anyone else ever catch the eye of their heroes?
self_made_human
C'est la vie
6d ago
If were talking about the effect of a ~one time experience, then comedowns arent necessarily relevant. We might imagine for example someone seeing "Wow, its possible to be happy" and that giving him hope in life. That hope might point down the abyss, but thats only measurable when you get there.
I think it's been quite reasonably established that the particular drugs you've mentioned so far aren't generally beneficial for depression, be it for a once off dose or on the regular.
There are limited circumstances where stimulants might help, such as in ADHD, where they provide mood benefits and increase functioning. That is not equivalent to endorsing cocaine for depression, it's a shitty choice in that regard. Too euphoric and addictive, wears off too quickly.
Yes, thats the point. The value of the cliche depends on not thinking you can outsmart it.
Are you aware of what doctors generally do? There's an endless list of substances that, if used recklessly or without sufficient knowledge, lead to harm. There's a drastic difference between giving someone opioids to someone in severe pain after a surgery and taking oxy to get high.
I feel no need to belabour that point, you go to a medical professional to get guided, targeted advice even for risky substances.
Why do you think apparently different drugs work in such similar ways here?
That would entail a full lecture on pharmacokinetics, receptor binding, neurotransmitters and so on.
self_made_human
C'est la vie
6d ago
Has anyone tried? In the manner of these studies I mean, not by just looking at addicts. People whove done heroin generally report that naive use is an experience beyond anything they had before. I would not be surprised if this influences people even months later. But it also might not, there are always those pescy details. E.g. maybe it overlaps too much with the alcohol high to show effects in our society.
I assure you that they're not effective solutions. Cocaine is highly addictive, and the comedowns more than make up for the very short-term euphoria. Heroin? That's akin to borrowing happiness from tomorrow at a very high interest rate, it doesn't end well.
We've got plenty of studies on the long-term effects of stimulants and opiates. They don't help with depression in any meaningful sense.
"Drugs can make you feel better when used responsibly" is hardly a new insight - the entire problem is the way they lead to non-responsible use.
I've only endorsed psilocybin in a therapeutic, observed context. It's not a particularly habit forming drug. More importantly, it has a short duration of acute effect, while appearing to durably reduce depression for months after a single dose. It's highly reductive to dismiss such advances as "Drugs can make you feel better when used responsibly".
Also curious what you think of this one.
Addictions aren't made alike. Some can be entirely benign, coffee, as Katja intentionally became dependent on, won't kill you, nor will it ruin your psycho-social functioning. ~Nobody has lost their job or family because they drink too much coffee.
Contrast that to becoming a lay-about stoner, a coke fiend, or a heroin addict.
self_made_human
C'est la vie
6d ago
Thank you!
I think the study does a reasonable job at providing ongoing therapeutic support, but I, idiosyncratically, have never found that therapy worked well for me. I did the bare minimum to keep them content, and didn't notice much of a change. The doses caused immediate and lasting changes in mood, before any followup therapy.
I’m interested in how the results between 10 mg and 25 mg will vary in the trial. I suspect that the higher dose benefits would be more noticeable and would last longer.
Hopefully, once the results are out, we'll have a proper understanding of the dose response curve at play here.
self_made_human
C'est la vie
6d ago
Its getting "scientific" now that the taboo has weakened, but... no shit it looks promising, youre literally trying drugs for mood. If the researcher cant make that look promising, how on earth did he get a PhD?
Is this a serious critique? Like, do you think that psychiatry of all professions isn't aware of the difference between "feeling happy" and "not being depressed"??
The scientists and doctors performing the studies are well aware that many drugs cause temporary and transient elevations in mood. Far fewer cause lasting improvements.
Prescribing cocaine and heroin is, unfortunately, not a viable cure for depression. Just making someone feel euphoria shortly after taking a drug isn't a "cure" or even a treatment.
I thought the part about pharmacokinetics was double as well, only realised now that one is about the nausea and one the whole thing.
I don't blame you, because the psychopharmacology is a lot of receptor names and binding sites that sound almost the same and vary in the last few letters or numbers.
self_made_human
C'est la vie
7d ago
Ah, gotcha.
Cannabis can induce outright psychosis and initiation of schizophrenic symptoms in people with genetic vulnerability towards it. The higher the dose, the higher the risk.
self_made_human
C'est la vie
8d ago
While I'm glad that weed helped you, I have good reason to believe that that's a rather unexpected/idiosyncratic response.
For most people with depression, I'd go as far as to say it's highly inadvisable:
Meta-analysis showed a higher risk of depression among cannabis users (OR: 1.29, 95% CI: 1.13–1.46).
This isn't entirely causal, as there's some evidence that people with a predisposition towards depression are more likely to try weed in the first place. Yet I think the evidence is there, and in particular, there's little evidence of it helping reduce depression.
ecstacy was also being trialled at the time in Australia, I wonder why it didn't take off like psilocybin
What I've heard on the grape-vine is that there are quite a few trials ongoing. I googled it, and they've got some big names involved.
A number of trials have concluded, with, as far as I can tell by eye-balling them quickly promising results.
Unfortunately, adoption just takes time. Not all psychiatrists are as open to the idea of psychedelics as I am. While not a psychedelic, ketamine was only relatively recently approved in the UK for depression, and it's a pain to acquire in the NHS.
Not to mention the lack of a profit motive. Most of them are unpatentable, hence pharma companies aren't really raring to go to produce them.
And I've met plenty of schizophrenics who were triggered by pot. It's not a gamble I'd suggest others take
I've looked at the figures, and that's very rare! Remember, you're looking at schizophrenics who you have reason to believe were triggered by pot. What we ought to be considering are people without known schizophrenia, what are the risks they develop it after trying pot?
That figure is very low. Probably in the sub 0.1% or lower range.
Even within schizophrenics, a study in Denmark found that only ~ 6-8% of schizophrenia cases were induced by weed.
There's also a strong dose dependence here, I would expect that even vulnerable people wouldn't be too affected by a small amount of weed. Unfortunately, potencies have only increased over time.
I wouldn't lose any sleep over it, but I'm not a big fan of weed because it can be habit forming, blunts cognition and just makes you lazy-ass drug if you take it regularly.
self_made_human
C'est la vie
8d ago
Reading the motte could certainly be damaging to some minors. I wonder how many people would participate if they had to send a picture of their driving license to the mods first.
I wouldn't mind, I'd just be looking at my own driving license.
Hmm.. I wonder if there's room for "creative" thinking here. Every new member is automatically promoted to mod status temporarily, verifies their own ID, and then resigns with dignity before becoming a normal participant.
self_made_human
C'est la vie
8d ago
I had had to head down to London twice to attend the sessions. Beyond that? Not much to say, it was a bog-standard NHS hospital.
You go in, they take your vitals and your measurements, primarily focusing on making sure your blood pressure is okay (psilocybin affects it, not that the risk is notable). By that point in time, you've gone through phone screening, but on arrival, they conduct drug screening. They're looking for any illicit substances that might confound their results.
Once you get the all clear, you swallow a dose, then head to a clinic room. I was alone, but I think I saw a few other people who were probably participants. They had extremely dull music playing, and offered me eye covers if I wanted them. I had a pressure cuff on, with continuous monitoring. A nurse would swing around every few minutes at the staff to make sure I was okay, but eventually I told her I felt fine and she didn't really bother. There was also a psychologist on staff, but I told them I didn't need anything in particular at the time.
Once 8 hours was up (I think they could have let me leave earlier, but I didn't want to risk it since I was unsure about the come down), they took another set of measurements and I was good to go.
Overall, very boring and clinical. Not that there was much else to do, it was a rainy day out there.
self_made_human
C'est la vie
8d ago
I'm sorry to hear that, and I'm glad to hear he got better.
However, the dose makes the poison. I presume he was using very large doses on a frequent basis, in conjunction with "massive quantities of THC". I can't speak authoritatively about the risks of psychosis from the former, at least not without reviewing the literature first, but the latter? If you have some kind of genetic predisposition, such as to schizophrenia, that will fuck you up. And the more drugs you throw into the mix..
In the case of psilocybin, for therapeutic doses, especially under supervision, the risks are minimal. I would never call psychedelics "harmless", but at least in this instance, when compared to how awful depression can be, I felt the odds were in my favor. Even something as 'benign' as SSRIs can cause mania shortly after initiation. Holding out for something that truly has no risk associated with it is a fool's errand I'm afraid.
self_made_human
C'est la vie
8d ago
I brought my own entertainment. The study design only offered "relaxing music" and an eye-cover if you were feeling overwhelmed. The music would have worked okay in an elevator or a Thai spa, but was absolutely not to my taste haha.
It's hard to blame them, really. Getting IRB approval for a clinical trial is a PITA on a good day, I strongly suspect that if they wanted to offer entertainment or a walk outside, they'd be raked over the coals, leaving aside the increase in liability and the demands on personnel. I'm certainly interested in trying shrooms in a more congenial environment!
We know this because we can, in fact, point to the gears in CPUs and RAM and do gear things with them, and this is in fact the best, most efficient way to manipulate and interact with them. This is not the case for minds: every workable method we have for manipulating and interacting with human minds operates off the assumption that the human mind is non-deterministic, and every attempt to develop ways to manipulate and interact with minds deterministically has utterly failed. There is no mind-equivalent of a programming language, a compiler, a BIOS, a chip die, etc.
The computer analogy is doing a lot of heavy lifting here, but it's carrying more weight than it can bear. Yes, if you take a soldering iron to your CPU, you'll break it. But the reason we know computers are deterministic isn't because we can point to individual transistors and say "this one controls the mouse cursor." It's because we built them from the ground up with deterministic principles, and we can trace the logical flow from input to output through layers of abstraction.
Compare that to any more tangled, yet mechanistic naturally occurring phenomena, and you can see that just knowing the fundamental or even statistical laws governing a complex process doesn't give us the ability to make surgical changes. We can predict the weather several days out with significant accuracy, yet our ability to change it to our benefit is limited.
The brain is not a tool we built. The brain is a three-pound lump of evolved, self-organizing, wet, squishy, recursively layered technology that we woke up inside of. We are not engineers with a schematic, I'd say we're closer to archaeologists who have discovered an alien supercomputer of terrifying complexity, with no instruction manual and no "off" switch.
The universe, biology, or natural selection, was under no selection pressure to make the brain legible to itself. You can look at our attempts at making evolutionary algorithms, and see how the outputs often appear chaotic, but still work.
Consider even LLMs. The basic units, neurons? Not a big deal. Simple linear algebra. Even the attention mechanism isn't too complicated. Yet run the whole ensemble through enormous amounts of data, and we find ourselves consistently befuddled by how the fuck the whole thing works. And yet we understand it perfectly fine on a micro level! Or consider the inevitable buildup of spaghetti code, turning something as deterministic (let's not get into race-conditions and all that, but in general) as code into something headache inducing at best.
And LLMs were built by humans. To be legible to humans. Neuroscience has a far more uphill struggle.
And yet we've made considerable progress. We're well past the sheer crudeness of lobotomies or hits on the head.
fMRI studies can predict with reasonable accuracy which of several choices a person will make seconds before they're consciously aware of the decision. We've got functional BCIs. We can interpret dreams, we can take a literal snapshot of your mind's eye. We can use deep brain stimulation or optogentics to flip individual neurons or neural circuits with reproducible and consistent effects.
As for "determinism of the gaps". What?
Two hundred years ago, the "gap" was the entire brain. The mind was a total mystery. Now, we can point to specific neural circuits involved in decision-making, emotion, and perception. We've moved from "an imbalance of humors causes melancholy" to "stimulating the subgenual cingulate can alleviate depressive symptoms." We've gone from believing seizures were demonic possession to understanding them as uncontrolled electrical storms in the cortex. The gaps where a non-material explanation can hide are shrinking daily. The vector of scientific progress seems to be pointing firmly in one direction. At this point, there's little but wishful thinking behind vain hopes that just maybe, mechanistic interpretation might fail on the next rung of the ladder.
I am frankly flabbergasted that anyone could come away with the opposite takeaway. It's akin to claiming that progress from Newton's laws to the Standard Model has somehow left us in more ontological and epistemic confusion. It has the same chutzpah as a homeopath telling me that modern medicine is a failure because we were wrong about the aetiogenesis of gastric ulcers.
This is not the case for minds: every workable method we have for manipulating and interacting with human minds operates off the assumption that the human mind is non-deterministic, and every attempt to develop ways to manipulate and interact with minds deterministically has utterly failed.
Citation needed? I mean, what's so non-deterministic about the advances I mentioned? What exactly do you think are the "non-deterministic" techniques that work?
self_made_human
C'est la vie
10d ago
In contact? Yes, I've got a message from her waiting for a reply right now.
Unfortunately, things soured somewhat. She stood me up/flaked on me multiple dates in a row, initially with valid explanations, and then nothing even approximating one. I was understandably pissed, but I was going to fly back to the UK in a few days, so I told myself not to bother. It was a much needed dousing with cold water, I have a disconcerting tendency to fall for people very quickly when the stars align.
I didn't think much of it later, but a few weeks down the road, she reached out to me and apologized for her behavior. I got the strong impression that things hadn't been going great for her, and there was something she wasn't telling me (not in, I'm sleeping with other people sense, just some kind of difficulty in life, I suspect she's depressed).
I was rather cool on the whole notion afterwards, but I've kept in touch. Even when I was head over heels, I knew on an intellectual level that it couldn't go anywhere right now, so we'll see how this pans out.
self_made_human
C'est la vie
10d ago
What's wrong with using fresh chili?
self_made_human
C'est la vie
11d ago
I have pointed questions about the kind of men she's "friends" with. They're so far from a representative sample that it's farcical.
self_made_human
C'est la vie
11d ago
I've never given it much thought, it's not something I've had to look up in depth.
self_made_human
C'est la vie
11d ago
Oops. I've let it through now.
self_made_human
C'est la vie
11d ago
This is all hopelessly confounded by the fact that, on the author's own admission, they were doing significant amounts of ketamine at the same time.
While I agree with the second paragraph, the first one has me scratching my head. Why would suffering have anything to do with the "unlearning gradient of an ML model" and, if so, how does an atom have anything to do with ML?
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