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Effect of LSD on reinforcement learning in humans (2022)
- riedel 4y agoNo 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?
- Out_of_Characte 4y ago75ug 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.
- isoprophlex 4y agoAlmost all drugs show higher potency when administered intravenously...
- Out_of_Characte 4y agoNo, IV 'only' has 100% bioavailability. This does not reflect potency.
- kweingar 4y ago> 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.
- throwawayadvsec 4y agoI'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
- pantalaimon 4y agoThis was intravenous though, so I’d assume the effect to be much stronger than when taken oral.
- phil-m 4y agoAre 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.
- tlb 4y agoThe 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.
- Broken_Hippo 4y agoI'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.
- throwaway50606 4y agoIf 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.
- throwawayadvsec 4y agoI 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?
- hackernewds 4y agofrom lots of experience, yes it can
- petemir 4y agoDoses 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.
- atkailash 4y ago
- d23 4y agoI 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.
- sva_ 4y agoPlacebos 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.
- diydsp 4y agoAlso 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/14469305 https://www.shroomery.org/forums/showflat.php/Number/1446930...
- retrac 4y agoThe 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.
- 2devnull 4y agoI 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.
- fbdab103 4y ago>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.
- Buhljingo 4y agoWould 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
- kweingar 4y agoWhere can I sign up to participate in a study that involves taking 200 ug of LSD? :)
- speed_spread 4y agoThere are multiple clinics on Wall Street, I hear.
- andrewinardeer 4y agoCIA
- thendrill 4y agoSame thing is observed with about 0.2 V and cpu overcloking... Suddenly there is a performance drop.
- nabla9 4y agoAnother 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.
- jimsimmons 4y agoComplete 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
- htag 4y ago> 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?
- GolDDranks 4y agoNot 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".
- jimsimmons 4y agoI 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
- robotresearcher 4y agoI 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’.
- GolDDranks 4y agoOh, so you mean like, supposing that NPI exists, an NPI problem? https://en.wikipedia.org/wiki/NP-intermediate 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.)
- tiku 4y agoI'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-persistent-anxiety-visuals-2022-4 https://www.insider.com/9-years-after-acid-trip-man-has-pers...
- kubb 4y agoNope, I don't have it.
- quchen 4y agoI'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".
- Broken_Hippo 4y agoI'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.
- jokowueu 4y agoAside 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
- 01100011 4y agoIt's more than snow. I had years after where walls would breathe. I still (decades later) have issues with black text on white backgrounds.
- elif 4y agoIt'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.
- droopyEyelids 4y agoThis 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.
- akvadrako 4y agoWhat 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.
- deleted 4y ago[deleted]
- tambourine_man 4y agoPlacebo is a powerful drug
- bentt 4y agoWere the subjects told “this is LSD” or were they told “this may be LSD and it may be a placebo”?
- perrylaj 4y agoI'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.
- photochemsyn 4y agoThis 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.
- s1artibartfast 4y agoThat'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
- photochemsyn 4y ago
- anigbrowl 4y agoThe 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.
- dr_dshiv 4y ago“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.”