Effect of LSD on reinforcement learning in humans (2022)(cambridge.org)
cambridge.org
Effect of LSD on reinforcement learning in humans (2022)
https://www.cambridge.org/core/journals/psychological-medicine/article/effect-of-lysergic-acid-diethylamide-lsd-on-reinforcement-learning-in-humans/28E41FEE97D3A8614C77DC54DF501489
102 comments
It's humorous to me that they bothered injecting saline into the control group here. I'm pretty sure anyone on earth would know whether or not they were on 75 micrograms of LSD, and the act of wondering whether you are or not is enough to induce panic. Pretty sure both groups would produce higher quality data in an unblinded study.
> I'm pretty sure anyone on earth would know whether or not they were on 75 micrograms of LSD
I wouldn’t. I have no idea how strong the effects of LSD are supposed to be based on a dose. I suspect only people who have taken LSD know really.
I wouldn’t. I have no idea how strong the effects of LSD are supposed to be based on a dose. I suspect only people who have taken LSD know really.
Assuming you have almost no prior knowledge about LSD, you might not be sure whether you're in the control group or not if you were actually given the placebo. If you received the LSD instead: 75ug is a very noticeable dose, I assure you you would have zero doubt whether you were in the control group or not.
In my case (80kg, male, slender/muscular), 75ug is the highest dose I can still, with significant and perpetual effort, appear sober to the uninitiated.
In my case (80kg, male, slender/muscular), 75ug is the highest dose I can still, with significant and perpetual effort, appear sober to the uninitiated.
> appear sober to the uninitiated
The initiated, however know exactly why your pupils are huge and you have that look on your face.
The initiated, however know exactly why your pupils are huge and you have that look on your face.
My pupils are fine at that dose. It's more subtle, it's the way I start looking at things (clouds, bark, grass, fur, my own hand) or zoning out while talking to someone. FWIW I never went above 100ug, nor do I feel like I want or need to. It gets quite intense once you learn how to let it.
Im guessing you aren't injecting it
Are you? Getting access to liquid LSD and the means to IM or IV it are certainly not typical, or anywhere near the prevalence of access to the oral form
I mean it's water soluble and you can get syringes and medicinal NaCl solution in a pharmacy just fine, so if you really want to go down that road it's no problem. Just begs the question why anyone would do that.
Thanks for explaining this. Perhaps 75ug in one group and 25ug in the other would have been a better test.
Blows my mind to think - the design of an experiment can have a huge impact on the outcome. I guess, clinical trials are just as much an art as they are a science.
Blows my mind to think - the design of an experiment can have a huge impact on the outcome. I guess, clinical trials are just as much an art as they are a science.
100 micrograms taken orally is the popular norm. What GP means is that you might not know as a reader, but if you were one of the test subjects you would very definitely know you were not in the control group. Likewise if you were in the control group but had taken LSD before you'd know you had drawn the short straw (unless the details of what was being tested were completely withheld).
Withholding the details of what was being tested would definitely not be informed consent.
~15/20ug is the dose an experienced person would percievably be able to notice, so microdosing is below this.
75ug is the lower end of the recreational scale. I first ever started with ~50ug (which honestly I'd recommend for beginners) and I had antidepressents in my system so it's effect is dulled a bit - and that was a giggly, eyes-full-of-wonder, oversaturated, and slight motion inpainting, wonderful experience. There was no way anyone mistakes that for being sober.
That said the come-up at any dose and any experience level is hilarious because everyone is always like "is it hitting yet?" as it progressively becomes more intense.
tl;dr - placebo could fool even some experienced users if they know they're being given a really low dose. The treatment group would absolutely know no matter how much experience you have.
https://psychonautwiki.org/wiki/LSD
EDIT: Sidenote, safety first friends. Always use two different reagents to test, and always have a plan to control anxiety in case of bad trips.
75ug is the lower end of the recreational scale. I first ever started with ~50ug (which honestly I'd recommend for beginners) and I had antidepressents in my system so it's effect is dulled a bit - and that was a giggly, eyes-full-of-wonder, oversaturated, and slight motion inpainting, wonderful experience. There was no way anyone mistakes that for being sober.
That said the come-up at any dose and any experience level is hilarious because everyone is always like "is it hitting yet?" as it progressively becomes more intense.
tl;dr - placebo could fool even some experienced users if they know they're being given a really low dose. The treatment group would absolutely know no matter how much experience you have.
https://psychonautwiki.org/wiki/LSD
EDIT: Sidenote, safety first friends. Always use two different reagents to test, and always have a plan to control anxiety in case of bad trips.
Even 15/20ug is quite a bit, which I would sometimes consider a minidose (depending on the setting).
I detect even down to 5-7ug LSD that I'm dosed (though I'm quite experienced with all kinds of dosages).
75ug is definitely tripping-level. No way someone couldn't detect that they are dosed, just the contrast/visual-enhancing qualities alone should be enough to detect that, maybe even some LSD-typical distortions can occur at that dose...
I detect even down to 5-7ug LSD that I'm dosed (though I'm quite experienced with all kinds of dosages).
75ug is definitely tripping-level. No way someone couldn't detect that they are dosed, just the contrast/visual-enhancing qualities alone should be enough to detect that, maybe even some LSD-typical distortions can occur at that dose...
Sorry but I have to ask. In what kinds of contexts did you become experienced? Is LSD in at least a gray area anywhere on earth? The country I come from that is an illegal drug, but it being a neuroplasticity enhancer is what attracted my attention. I've also read about microdosing which can enhance focus or creativity.
Can it be prescribed for treating depression or other mental deficits or the approvals are not at that stage yet?
Recreationally dosing in all kinds of settings and doses (e.g. microdosing in almost any setting on very different doses etc.). I have accurately tested LSD, so I know the exact dose I'm taking. Also I've done a bit of research of various scientific articles.
It's unfortunately not really legal though where I'm living.
AFAIK there are a few psychiatrists/researchers around the world where it's approved for clinical studies, where you could try it in a clinical setting. But unfortunately you're often still on your own with trying it. I tried microdosing it for treating ADHD, but I'm not really sure if it really helped there, and I'm back on the usual medications, YMMV though, as LSD has mild stimulant properties as well.
I may try a combination/mix of LSD and other ADHD medications in the near future though.
It being a neuroplasticity enhancer doesn't necessarily mean that it's enhancing in a good/healthy way. I noticed that my thoughts/imagination have gone a bit more "visual" (not sure if that's really the right term), I'm not sure if it really made me more creative. I think for me it mostly manifested my mind further and I'm a bit more in tune with nature etc. (much more conscious of all the "ecocrimes" humanity is doing).
This may not always be a good thing if e.g. you're prone to conspiracy theories. It can also mean that it's promoting growth in areas in the brain that shouldn't be connected (e.g. leading to psychosis), it's still a powerful substance which should be handled carefully.
But in general I think it still takes some time until this is a clinically approved substance. I think it will likely be for stuff like depression or PTSD or generally disorders originating mostly in the frontal lobe. I have certainly noticed the antidepressive properties of it (although I never had a real depression while taking it).
It's unfortunately not really legal though where I'm living.
AFAIK there are a few psychiatrists/researchers around the world where it's approved for clinical studies, where you could try it in a clinical setting. But unfortunately you're often still on your own with trying it. I tried microdosing it for treating ADHD, but I'm not really sure if it really helped there, and I'm back on the usual medications, YMMV though, as LSD has mild stimulant properties as well.
I may try a combination/mix of LSD and other ADHD medications in the near future though.
It being a neuroplasticity enhancer doesn't necessarily mean that it's enhancing in a good/healthy way. I noticed that my thoughts/imagination have gone a bit more "visual" (not sure if that's really the right term), I'm not sure if it really made me more creative. I think for me it mostly manifested my mind further and I'm a bit more in tune with nature etc. (much more conscious of all the "ecocrimes" humanity is doing).
This may not always be a good thing if e.g. you're prone to conspiracy theories. It can also mean that it's promoting growth in areas in the brain that shouldn't be connected (e.g. leading to psychosis), it's still a powerful substance which should be handled carefully.
But in general I think it still takes some time until this is a clinically approved substance. I think it will likely be for stuff like depression or PTSD or generally disorders originating mostly in the frontal lobe. I have certainly noticed the antidepressive properties of it (although I never had a real depression while taking it).
Just a question but are you able to accurately measure down to 5-7ug to know that's how much you're testing? As I'm familiar with, tabs and other dosing with exception to volumetric are well known for large discrepancies in reported vs actual dose
The most accurate method is to have it in liquid form and dose that way.
Yeah liquid dosing, pretty sure I did it right, got accurate dosed acid as well (which is rare AFAIK). But even if it wouldn't super accurate, it's much more likely to be less acid than more.
But I'm quite hypersensitive to substances in general I think, so my experience may not be representative.
But I'm quite hypersensitive to substances in general I think, so my experience may not be representative.
> ~50ug (which honestly I'd recommend for beginners)
So says the guy who took LSD while on antidepressents.
> EDIT: Sidenote, safety first friends.
possibly I'm high but I find this rather amusing. Enjoy but don't play doctor until you get your degree.
So says the guy who took LSD while on antidepressents.
> EDIT: Sidenote, safety first friends.
possibly I'm high but I find this rather amusing. Enjoy but don't play doctor until you get your degree.
> possibly I'm high but I find this rather amusing. Enjoy but don't play doctor until you get your degree.
I'm not saying it's safe. In fact I think there's significant potential for harm from careless use of psychs, and I can't recommend it from a safety perspective.
That being said, if you were going to use it - and this goes for any drug - you MUST test it. You cannot OD on 4 tabs of LSD. If it's actually 2C-B (it's half the price) then you could die.
--
If you're on the fence - don't take it.
If you were going to anyway - take it in a way that minimizes harm.
I'm not saying it's safe. In fact I think there's significant potential for harm from careless use of psychs, and I can't recommend it from a safety perspective.
That being said, if you were going to use it - and this goes for any drug - you MUST test it. You cannot OD on 4 tabs of LSD. If it's actually 2C-B (it's half the price) then you could die.
--
If you're on the fence - don't take it.
If you were going to anyway - take it in a way that minimizes harm.
hey, it was and is all super friendly.
and I am not saying it is unsafe. (have no idea, never partook. naturally exhibited behavior that apparently the "initiated" will interpret as micro-cruising. just this very day was attentively looking at bark, but thankfully no one caught me in the act.)
so can we agree as hackernews friends that you exhibited questionable judgement (all ok, who is perfect) and you shouldn't go around giving advice on taking mind altering chemicals?
"lsd is great, you should try it" is fine. "take this much and if you're on this is fine. i survived" is not, imho.
and I am not saying it is unsafe. (have no idea, never partook. naturally exhibited behavior that apparently the "initiated" will interpret as micro-cruising. just this very day was attentively looking at bark, but thankfully no one caught me in the act.)
so can we agree as hackernews friends that you exhibited questionable judgement (all ok, who is perfect) and you shouldn't go around giving advice on taking mind altering chemicals?
"lsd is great, you should try it" is fine. "take this much and if you're on this is fine. i survived" is not, imho.
> "lsd is great, you should try it" is fine. "take this much and if you're on this is fine. i survived" is not, imho.
I guess I should have worded it differently.
The dose I took was actually ~1/2 a tab, as compared to starting with a full tab (the exact ug is basically impossible to know). Some people would view this as "wasting it". I think starting with a full tab would likely be overwhelming for some people, but I don't mean to say any ug is "safe" or recommended. It's just that a lot of people are going to do it anyway, and if they do I'd rather they have the best chance at being safe. This stuff isn't really well medically documented so it's basically all off "experiences".
I haven't used it in years, and I wasn't doing super well at the time.
I guess I should have worded it differently.
The dose I took was actually ~1/2 a tab, as compared to starting with a full tab (the exact ug is basically impossible to know). Some people would view this as "wasting it". I think starting with a full tab would likely be overwhelming for some people, but I don't mean to say any ug is "safe" or recommended. It's just that a lot of people are going to do it anyway, and if they do I'd rather they have the best chance at being safe. This stuff isn't really well medically documented so it's basically all off "experiences".
I haven't used it in years, and I wasn't doing super well at the time.
tbh am possibly too risk averse to have taken lsd on other medication myself, much less a-d. Depression sucks. Glad and hope you are doing better these days.
You must be thinking of something like 25B-NBOMe, not 2C-B. 2C-B is not potent enough to be dosed on blotter, and its lethal dose is unknown but expected to be quite high.
https://en.m.wikipedia.org/wiki/2C-B
As far as i understand, psylocin and LSD have never been shown to be dangerous, in combination with any drug with possible exception to MAOI _maybe_. There are interactions that make it less intense and interactions that make it more intense. The only real danger is that you'll do something bad while in the state, not that the state will actually harm you.
So it's perfectly reasonable for someone to take a low dose of LSD while on antidepressants. The worst I've ever heard of occurring is that you just won't feel it at all. It's a targeted agonist of multiple serotonin receptors, i don't believe it actually releases any large flood of serotonin. Something like MDMA though _is_ very dangerous to take with SSRIs due to serotonin syndrome.
I've known many people to do psychedelics while on antidepressants and non of them have ever approached the levels of danger or concern that I've seen for people doing MDMA while not on anything else. The traditional psychedelics (LSD, shrooms) are remarkably safe and there's no reason to act like this person is being dumb or disingenuous for doing them in their circumstance. If you have research to the contrary I'd certainly welcome the opportunity to learn
So it's perfectly reasonable for someone to take a low dose of LSD while on antidepressants. The worst I've ever heard of occurring is that you just won't feel it at all. It's a targeted agonist of multiple serotonin receptors, i don't believe it actually releases any large flood of serotonin. Something like MDMA though _is_ very dangerous to take with SSRIs due to serotonin syndrome.
I've known many people to do psychedelics while on antidepressants and non of them have ever approached the levels of danger or concern that I've seen for people doing MDMA while not on anything else. The traditional psychedelics (LSD, shrooms) are remarkably safe and there's no reason to act like this person is being dumb or disingenuous for doing them in their circumstance. If you have research to the contrary I'd certainly welcome the opportunity to learn
I actually disagree somewhat.
So I likely overdid one particular month....
But I have (likely) permanent HPPD - particularly when I take my adhd meds I can get some motion inpainting, geometry visuals, and turning off the lights at night looks like a "shower of colors", and also white looks simultaneously red/blue/green/purple (the color you see after looking at a really bright light and looking away).
It's not currently causing issues for me but it is a real thing. MRI shows no abnormalities, eye exam also shows nothing odd. The visuals are almost identical to light lsd visuals. I'm 100% aware they aren't "real", none of my doctor's believe it's psychosis.
I'm also 100% convinced that chronic psychedelic and possibly chronic marijuana usage contributes to schizophrenia.
And I'm certain you can get real PTSD from a bad trip.
I have no idea what extent the medication combo did, but with or without antidepressents, I don't want to say it's "safe". I'm not saying it's dangerous, but I don't think it's harmless.
Also smoking marijuana with lsd makes it like 10x more intense, and I have a feeling that also has a chance at shifting the harm potential.
So I likely overdid one particular month....
But I have (likely) permanent HPPD - particularly when I take my adhd meds I can get some motion inpainting, geometry visuals, and turning off the lights at night looks like a "shower of colors", and also white looks simultaneously red/blue/green/purple (the color you see after looking at a really bright light and looking away).
It's not currently causing issues for me but it is a real thing. MRI shows no abnormalities, eye exam also shows nothing odd. The visuals are almost identical to light lsd visuals. I'm 100% aware they aren't "real", none of my doctor's believe it's psychosis.
I'm also 100% convinced that chronic psychedelic and possibly chronic marijuana usage contributes to schizophrenia.
And I'm certain you can get real PTSD from a bad trip.
I have no idea what extent the medication combo did, but with or without antidepressents, I don't want to say it's "safe". I'm not saying it's dangerous, but I don't think it's harmless.
Also smoking marijuana with lsd makes it like 10x more intense, and I have a feeling that also has a chance at shifting the harm potential.
Were the subjects told “this is LSD” or were they told “this
may be LSD and it
may be a placebo”?
I'm not sure how global the practice is, but at least in the US, you're briefed on the study as part of patient consent. They clearly tell you that nature of the study, including details about blinding, placebos that study participants may get instead of the active chemical, etc.
Informed consent was codified into international law [1] in response to Nazi and Japanese human experiments. There's a few notable exceptions like China (signed but not ratified internally) and in some cultures it may not be emphasized enough to doctors in training but it's pretty universally understood in medical ethics that lying to patients is a line we should not cross.
[1] https://en.wikipedia.org/wiki/International_Covenant_on_Civi...
[1] https://en.wikipedia.org/wiki/International_Covenant_on_Civi...
That only requires consent, not informed consent. AFAIK, if someone consents to being experimented on, that law does not require you to fully inform them of the experiment, and certainly not to the degree that a typical IRB in the US requires.
Placebo is a powerful drug
75 is a fairly mild dose, and people can placebo themselves into some pretty extreme states
I disagree about 75 being a fairly mild dose. For a 200lbs male maybe. For a 100lbs female definitely not.
LSD doesn't scale with bodyweight, you take the same amount no matter if you're 100 or 300lbs. Apart from that, 70mcg is a mild dose on context of a regular recreational dose of 150-250mcg, but I agree that 70mcg by itself will absolutely significantly impair an inexperienced user and there is a zero percent chance you would conflate 70mcg with placebo.
in what world is 250ug of lsd considered a “regular recreational” dose? The standard 100-125 that you get on most paper tabs is plenty to have a strong trip for the vast majority of people and 200-250ug is going to be way too strong for everyone except for the most experienced people
I think most people get over-sold blotters. Every now and then there's a study checking how much LSD is actually on sold-as-200ug blotters, and it's typically 60-80. This also leads to heavy overdoses when getting your hands on actual 200ug blotters...
I remember that story about Jim Morrison going missing (before a gig or recording or something?) - he was eventually found under a bed, and all he could say was "ten thousand mics!"
Nah definitely not, maybe you haven't had good/accurately dosed acid yet.
75 is the usual dose that is marketed as 100ug tabs (averagely roughly 80% of the marketed dose).
It's definitely noticable, even for unexperienced (I even recommend a lower dose to begin with).
75 is the usual dose that is marketed as 100ug tabs (averagely roughly 80% of the marketed dose).
It's definitely noticable, even for unexperienced (I even recommend a lower dose to begin with).
This isnt necessarily true. There is some study out there where subjects were either given saline, or a moderate dose of LSD, and it was only like 60% of subjects were able to tell which was which.
What is a moderate dose and which 60% ?
If someone had never tripped on LSD and was given a placebo, they might think it's LSD because how would they know.
But if you know what an LSD trip is, I don't think it's possible to mistake a placebo for it.
If someone had never tripped on LSD and was given a placebo, they might think it's LSD because how would they know.
But if you know what an LSD trip is, I don't think it's possible to mistake a placebo for it.
[deleted]
No expert, but I had some immediate questions when reading this. Wasn't the dose high enough to be easily distinguishable from the placebo without any experience? Why not some other drug a palcebo? Is single blind design actually advisable in such a study? Can someone enlighten me?
Placebos in psychedelics studies are rightfully often laughed about, but if the placebo group never took LSD before, it may indeed not be obvious to them if they got the drug or not.
The potency of the placebo effect with psychoactive drugs is pretty remarkable. It also illustrates an interesting effect about the cultural influence on intoxication. It's one of the more easily repeatable placebo experiments.
If you give a bunch of young adults who have never drunk alcohol some "alcohol" and then observe them, they both a) act drunk b) act drunk, according to their expectations about alcohol. (People who report that they believe alcohol makes people more social act more social, those who report that they believe it makes people withdrawn, become morose, etc.)
Another repeated finding, in both placebo and non-placebo groups, is that the alcohol takes effect before it would... take effect. People change behaviour almost immediately. I've noticed that with a drink myself; I'm feeling the drink before I possibly could have absorbed it. It also works the other way too -- a group of actually drunk people behave more sober when you've told them it was just rum-flavoured water, not actual alcohol.
If you give a bunch of young adults who have never drunk alcohol some "alcohol" and then observe them, they both a) act drunk b) act drunk, according to their expectations about alcohol. (People who report that they believe alcohol makes people more social act more social, those who report that they believe it makes people withdrawn, become morose, etc.)
Another repeated finding, in both placebo and non-placebo groups, is that the alcohol takes effect before it would... take effect. People change behaviour almost immediately. I've noticed that with a drink myself; I'm feeling the drink before I possibly could have absorbed it. It also works the other way too -- a group of actually drunk people behave more sober when you've told them it was just rum-flavoured water, not actual alcohol.
>People change behaviour almost immediately. I've noticed that with a drink myself; I'm feeling the drink before I possibly could have absorbed it.
I have noticed a similar thing in myself. The second I taste alcohol, it is like a switch was flipped, and I am now "drinking mode". Presumably some strong state-dependent learning. On the other hand, if I am physically dehydrated and drink a glass of water, I immediately feel better even though it must surely take several minutes for the water to start being absorbed.
I have noticed a similar thing in myself. The second I taste alcohol, it is like a switch was flipped, and I am now "drinking mode". Presumably some strong state-dependent learning. On the other hand, if I am physically dehydrated and drink a glass of water, I immediately feel better even though it must surely take several minutes for the water to start being absorbed.
I suspect the placebo effect has limited duration for those who are experienced with psychedelics. I can imagine wrongly thinking you’ve been dosed for about 90 minutes, but after that one would surely know, at least for LSD.
Also people vary on response to all pharmas. Some are simply "hardheads." [0] And this can vary with concomitant medications. So it's inportant to capture these results.
[0] not the most scientific reference but the term "hardhead" is useful here: https://www.shroomery.org/forums/showflat.php/Number/1446930...
[0] not the most scientific reference but the term "hardhead" is useful here: https://www.shroomery.org/forums/showflat.php/Number/1446930...
> Wasn't the dose high enough to be easily distinguishable from the placebo without any experience?
This was my first thought. There’s no way that anybody would mistake 75 ug of LSD for placebo.
This was my first thought. There’s no way that anybody would mistake 75 ug of LSD for placebo.
The placebo here was saline (no physiological effect). Sometimes they give amphetamines as a placebo so the control group also feel that something is different. But I’d expect that to affect RL hyperparameters too.
I'm not sure about this.
I'm a big guy, I barely feel 100 ug, if I didn't know what LSD was like I could easily not notice
This was intravenous though, so I’d assume the effect to be much stronger than when taken oral.
Are you sure you have really taken 100ug? The blotters these days are very often quite a bit less, although marketed as 100ug.
100ug should be enough for most for a good trip.
I'd think there were two ways to produce this.
The first would be to not disclose the dose. If you don't know the dose, you might just assume it is a low dose and you aren't getting effects. This is especially easy to pull off since a lot of folks know about microdosing - which usually has the goal of not-too-much-hallucination.
Second, you can get folks new to LSD in combination with the above.
I'd think that the issue with giving another drug is that we wouldn't know how that drug is going to affect the outcome. You still need the baseline of sober folks to compare to, and given them a fake dose means that the ones that will have the placebo effect, will.
The first would be to not disclose the dose. If you don't know the dose, you might just assume it is a low dose and you aren't getting effects. This is especially easy to pull off since a lot of folks know about microdosing - which usually has the goal of not-too-much-hallucination.
Second, you can get folks new to LSD in combination with the above.
I'd think that the issue with giving another drug is that we wouldn't know how that drug is going to affect the outcome. You still need the baseline of sober folks to compare to, and given them a fake dose means that the ones that will have the placebo effect, will.
If you have any hallucinations at all, you're not microdosing. Microdosing is right before the tipping point of recognizing you took something at all. It should be recognizable from long-term effects, not immediately.
I wonder if there is more data about this.
A while ago I've microdosed 1 to 2g of fresh truffles(which should not induce a trip), a few days/weeks after a real trip, and I had some hallucinations, which should not have happened
IDK, is it possible that a microdose could trigger some kind of a release of a previous buildup of some hallucinogens?
A while ago I've microdosed 1 to 2g of fresh truffles(which should not induce a trip), a few days/weeks after a real trip, and I had some hallucinations, which should not have happened
IDK, is it possible that a microdose could trigger some kind of a release of a previous buildup of some hallucinogens?
Doses seem to accumulate, that’s why you need days off, too, and they recommend not to mix macro and micro doses. I’ve read somewhere that after a big dose you should wait ~1 month for the effects to wean.
from lots of experience, yes it can
Micro dosing (as the name suggests) is more about the input dose, than the output results
Not really, it is about achieving some effect with a specific dose. The effect is about some improvements in your life without tripping. If you're tripping, you're not microdosing.
I think this would be an issue in any study. I assume the purpose of a double blind is not to convince those in the treatment group they have taken nothing — it’s to convince those in the placebo group they’ve taken something, and then measure that placebo effect.
75ug would definitely be 'noticeable' if you took it sublingual. But this was an IV so I wouldnt know how much dilution there would be before passing the blood brain barrier. My best guess is that it would lower effective dose and how strong thr initial onset was.
Almost all drugs show higher potency when administered intravenously...
No, IV 'only' has 100% bioavailability. This does not reflect potency.
The double-blind thing seems a little pointless here, 75ug is on the small end of dosage but close to the informal 'standard' dose of 100uh, and intravenous delivery means very rapid onset compared to oral administration. It might have been more interesting to try with low doses that wouldn't necessarily give the feeling of tripping (visual artifacts etc).
The result is interesting but feels a bit like a formal statement of what everyone already knew to be distinctive about psychedelics. The actual numbers don't seem that dramatic. I'm a little skeptical about the drive to rehab LSD as a therapeutic product - both because I have doubts about mediation of psychedelic experience by clinicians, and because of the relatively long metabolic half-life, with a psychoactive dose typically lasting 8-12 hours. The combination of LSD and for-profit healthcare delivery as practiced in the US seems like an extremely poor match.
The result is interesting but feels a bit like a formal statement of what everyone already knew to be distinctive about psychedelics. The actual numbers don't seem that dramatic. I'm a little skeptical about the drive to rehab LSD as a therapeutic product - both because I have doubts about mediation of psychedelic experience by clinicians, and because of the relatively long metabolic half-life, with a psychoactive dose typically lasting 8-12 hours. The combination of LSD and for-profit healthcare delivery as practiced in the US seems like an extremely poor match.
“Computational modelling revealed that the most pronounced effect of LSD was the enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploration. Reinforcement sensitivity differed by phase.
Conclusions
Increased RL rates suggest LSD induced a state of heightened plasticity.”
Conclusions
Increased RL rates suggest LSD induced a state of heightened plasticity.”
Would love to see this type of experiment performed across different dosages, 25 μg -200 μg. I think the "positive" effects would take a big, sudden drop after a certain threshold
Where can I sign up to participate in a study that involves taking 200 ug of LSD? :)
There are multiple clinics on Wall Street, I hear.
Another experiment immediately after the LSD trip is over and the drug has been metabolized. Something like 24h - 48h afterwards.
I find that the most positive cognitive effects come directly afterwards, when the mind is clear. It's like opposite of hangover.
I find that the most positive cognitive effects come directly afterwards, when the mind is clear. It's like opposite of hangover.
Same thing is observed with about 0.2 V and cpu overcloking... Suddenly there is a performance drop.
This is a rather strange definition of 'learning', a better term would be 'behavioral modification.' Here's a definition of the practice:
> "From an affective neuroscience perspective, our understanding of psychiatric illness may be advanced by neuropsychological test paradigms probing emotional processes. Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment associations through trial and error and then reverse them. (2009 Cambridge Pyschological Medicine, Dickstein et al.)"
This is pretty low-level stuff, e.g. 'learning' that red means stop and then 'relearning' that red means go, etc. The authors claim to have developed evidence that LSD is associated with plasticity in healthy humans suffering no psychological disorders.
It's an interesting study, I suppose. Psychedelics are often called 'mind-expanding' and it's possible that the underlying neurochemical mechanism of action facilitates breaking out from fixed behavior patterns. This might also explain some of the reasons why authoritarian governments don't like psychedelics as they might encourage a loss of faith in authorities, or cause religious fundamentalists to reconsider their belief systems etc.
After all, if you can't necessary trust your sensory organs to give you reliable information about the world around you due to the influence of a complex molecule on a receptor protein in your brain, perhaps blind faith in the pronouncements of politicians, priests, and media talking heads is not justified either?
In terms of learning, however, I've always thought that most notable psychedelic effect was the development of good three-dimensional visualization of complex objects, such as electrical fields or proteins and DNA and things like that. Such visual effects are generally associated with higher doses however, which are a bit tricky to manage safely, and so require special attention to optimal set and setting.
> "From an affective neuroscience perspective, our understanding of psychiatric illness may be advanced by neuropsychological test paradigms probing emotional processes. Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment associations through trial and error and then reverse them. (2009 Cambridge Pyschological Medicine, Dickstein et al.)"
This is pretty low-level stuff, e.g. 'learning' that red means stop and then 'relearning' that red means go, etc. The authors claim to have developed evidence that LSD is associated with plasticity in healthy humans suffering no psychological disorders.
It's an interesting study, I suppose. Psychedelics are often called 'mind-expanding' and it's possible that the underlying neurochemical mechanism of action facilitates breaking out from fixed behavior patterns. This might also explain some of the reasons why authoritarian governments don't like psychedelics as they might encourage a loss of faith in authorities, or cause religious fundamentalists to reconsider their belief systems etc.
After all, if you can't necessary trust your sensory organs to give you reliable information about the world around you due to the influence of a complex molecule on a receptor protein in your brain, perhaps blind faith in the pronouncements of politicians, priests, and media talking heads is not justified either?
In terms of learning, however, I've always thought that most notable psychedelic effect was the development of good three-dimensional visualization of complex objects, such as electrical fields or proteins and DNA and things like that. Such visual effects are generally associated with higher doses however, which are a bit tricky to manage safely, and so require special attention to optimal set and setting.
That's interesting, I've never heard about it attenuating 3D visualization capability. I know that some people are good at it and some people are not capable. My understanding of psychedelics is based in the plasticity model, so I felt or assumed that 3D visualization was just a flexing or practice using those skills, not acquisition of new skills
It might be plasticity in the sense that realizing those skills are worth spending time and energy on could be a result of ingesting such substances.
I'm more scared of LSD than ever before, after hearing about that you see "scanlines" for ever after using it. Anyone got this after?
https://www.insider.com/9-years-after-acid-trip-man-has-pers...
https://www.insider.com/9-years-after-acid-trip-man-has-pers...
"My whole mouth went numb" This is a very strong indication for taking NBOME instead of LSD. From the article: "Looking back, I'm pretty certain that what I tried was not LSD." LSD would never numb your mouth. Just Google "LSD mouht numb reddit". Also, there's no lethal does of LSD, NBOM can easily kill you or screw you up just like in the article.
Everyone should always test thier substances before taking them to prevent these stories.
So do not fear LSD, fear NBOME.
Everyone should always test thier substances before taking them to prevent these stories.
So do not fear LSD, fear NBOME.
Yup metallic taste almost certainly NBOME or another RC.
But even so, I didn't have any of these side effects from NBOME, even temporarily. It was just a shorter, more chaotic acid trip with a different kind of visuals and more cohesive consciousness/memory.
I have no regrets about LSD or any other chems I experienced. In fact I credit them with enabling me to finally understand what love is (and isn't).
But even so, I didn't have any of these side effects from NBOME, even temporarily. It was just a shorter, more chaotic acid trip with a different kind of visuals and more cohesive consciousness/memory.
I have no regrets about LSD or any other chems I experienced. In fact I credit them with enabling me to finally understand what love is (and isn't).
Or rather, make sure you know what you're taking. Chemical reagent tests exist, so do fentanyl, NBOMe, bromo-dragonfly. Responsible use is no overly cautious joke.
I'm neither a fan of drug glorification nor FUD. The link is from someone who took lots of different substances very irresponsibily,
> I got some acid from a friend of a friend. It was some sort of pink substance smudged on the back of an Altoid, and I just popped the whole mint in my mouth.
AKA "a completely unknown pill with a friend's opinion".
> I got some acid from a friend of a friend. It was some sort of pink substance smudged on the back of an Altoid, and I just popped the whole mint in my mouth.
AKA "a completely unknown pill with a friend's opinion".
I've done a fair amount of LSD, over years. I'm in my mid-40s, and it hasn't been all that long.
I've never had this. My partner - the person I've done it with the most - hasn't either. Nor have I known anyone.
That said, it isn't like I think this person is lying, but that it is something rare, as the article admits to at the end.
I'm not really trying to make you less scared - you do you, and don't do a drug you don't want to do - but trying to give some perspective.
I've never had this. My partner - the person I've done it with the most - hasn't either. Nor have I known anyone.
That said, it isn't like I think this person is lying, but that it is something rare, as the article admits to at the end.
I'm not really trying to make you less scared - you do you, and don't do a drug you don't want to do - but trying to give some perspective.
Thanks for the article. It sounds very similar to what I dealt with after I took two tabs of what probably was DOx sold as LSD around 1990. Nearly 24 hour, intense trip with long term visual effects, depersonalization and derealization, and severe anxiety for years after. Funnily enough I also received a bipolar diagnosis.
Aside from fud the only thing that is known among psychadelic users is visual snow ( one of the hallmarks of HPPD) . this sometimes happens after extremely high doses of psychadelics
It's more than snow. I had years after where walls would breathe. I still (decades later) have issues with black text on white backgrounds.
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Worst about visual snow is that the night sky is a busy mess and I never know if a light dot is actually real. Definitely too much LSD for to long
You can test your LSD. I think this is a key part missing in many horror stories. They didn't have clarity in what they were using.
In Vienna they have a peg that will use a mass spectrometer and also give you a estimate on the strength of your tab. Very amazing form of harm reduction.
"The mind makes it real"
If you search for patterns in your "input data" you will find them. If you search for the patterns enough, your "mind" will automate the process. Then you have those "patterns" in your "normal" perception.
An example: if focus on the noice floor of you hearing for a few days you will begin to perceive tinnitus.
My hypothesis would be that the man from the article took the drug, became scared cause he perceived scan lines in is visual perception, then placed loots of attention on the scan lines to determine if they would go away. The attention he placed on the scan lines strengthened the perceptions and now he can’t undo the conditioning he did to his visual processing system.
If you search for patterns in your "input data" you will find them. If you search for the patterns enough, your "mind" will automate the process. Then you have those "patterns" in your "normal" perception.
An example: if focus on the noice floor of you hearing for a few days you will begin to perceive tinnitus.
My hypothesis would be that the man from the article took the drug, became scared cause he perceived scan lines in is visual perception, then placed loots of attention on the scan lines to determine if they would go away. The attention he placed on the scan lines strengthened the perceptions and now he can’t undo the conditioning he did to his visual processing system.
* It sounds like it an NBOME, which is known for being less forgiving at higher doses than LSD. I think the lesson here is to test your drugs.
* I've also noticed people that are interested in tripping multiple days in a row tend to have worse outcomes than those that pace themselves. He credits the second trip with developing the problems.
* His primary complaint before he started taking drugs is that trauma lead him to become withdrawn. His primary complain now is that he feels a tendency to withdrawal from his family. It sounds like his biggest problem is the same before and after HPPD.
* I've also noticed people that are interested in tripping multiple days in a row tend to have worse outcomes than those that pace themselves. He credits the second trip with developing the problems.
* His primary complaint before he started taking drugs is that trauma lead him to become withdrawn. His primary complain now is that he feels a tendency to withdrawal from his family. It sounds like his biggest problem is the same before and after HPPD.
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Nope, I don't have it.
Complete BS study. Increased exploration reduces reward learning rate. That’s the whole point of explore-exploit trade off which is at least NP hard.
The way they refer to RL dynamics as “RL rates” is also a give away that these people don’t understand RL. I’ll leave the evaluation of their cognitive science merit to people knowledgeable in that area
The way they refer to RL dynamics as “RL rates” is also a give away that these people don’t understand RL. I’ll leave the evaluation of their cognitive science merit to people knowledgeable in that area
> at least NP hard
Excuse me, I have a question. I was under the impression something is either NP hard or it is not. When you say "at least NP hard" it suggests there are levels beyond NP. Am I misinformed, or am I misunderstanding you?
Excuse me, I have a question. I was under the impression something is either NP hard or it is not. When you say "at least NP hard" it suggests there are levels beyond NP. Am I misinformed, or am I misunderstanding you?
Not the parent, but you are correct in that NP-Hard includes also harder problems than the problems in NP. "At least NP-hard" is just "NP-hard".
I read that differently. There are harder problems in NP, in the same way there are 7ft tall people in the set of people over 6ft tall. So ‘at least NP hard’ I understood as ‘in NP but maybe in a subset of NP that is harder’.
Oh, so you mean like, supposing that NPI exists, an NPI problem? https://en.wikipedia.org/wiki/NP-intermediate
> There are harder problems in NP
That is an unresolved question. It might turn out that every problem in NP is equally hard. (Up to a polynomial translation cost.)
> There are harder problems in NP
That is an unresolved question. It might turn out that every problem in NP is equally hard. (Up to a polynomial translation cost.)
Thanks for the better information!
I meant to say that it being NP hard was the beginning of issues. Even if there was a polynomial time algorithm for it there are other can of worms to deal with.
But I was wrong ultimately
But I was wrong ultimately