Microdosing study shows the placebo effect of taking psychelics
ft.com
ft.com
Without venturing a positive or negative opinion either way: I clicked the original article, couldn’t see the content without paying, so I left. Clicked the link to presumably bypass the paywall, and couldn’t pass the bot detection in a few seconds as a human on my preferred reading device, so I left.
Now I don’t want to bother reading the article at all, and took the time to write a comment here instead.
Now, instead of essential oils, let’s say I did the same thing with a drug that is popular in Silicon Valley, and instead of a Facebook mom group, it’s hacker news.
Are you trying to imply that the same is true for essential oils? This seems like a false equivalency/strawman situation.
Are there even stories about anyone getting cured via microdosing? :o
It is really tough to admit to yourself and others that what your felt wasn't some magical experience, it was just your brain making it up.
I would quote Albus Dumbledore here though: “Of course it is happening inside your head, Harry, but why on earth should that mean that it is not real?”
I took a "heroic dose" of psilocybin, and during the ~4 hour trip I fell asleep and I was convinced I had died. I re-experienced my forgotten birth and felt the pain of my circumcision. I experienced a bunch of unexplainable things, fractal patterns and music, and explored a Interstellar(2014)-like tesseract where I could choose any place in time to return to. I decided to return to myself in the present time, rather than pass on to whatever comes after my life.
I awoke in a puddle of urine and vomit. My body felt like it had been hard-reset and I felt little pains here and there which I had completely forgotten about and my brain had just become used to and ignored. I immediately felt better about my mess of a life, and happy that it's what I get to work with and make better. I used that positive momentum to get pumped about Cognitive Behavioral Therapy, where I did a lot of good work on myself.
For therapeutic effect of psychedelics, I think the uncomfortable mind-body separation experience is necessary.
Then I took some LSD and had a mild trip with a friend and literally the next morning I felt happy and energetic. From that point on I have not been anywhere near the depression I had before. Now I just have the normal ups and down of life abs feel perfectly capable of dealing with the world.
But just to agree with you, not everybody needs a heroic dose, and as the name implies, it's a dose where there is the possibility of stuff going very wrong - but one of the morals of psychedelics, (and indeed life itself because reality is "the strongest tab I never took"), is that you have to get to that place of completely surrendering and offering yourself up in order for you to be really transformed.
And the funny thing is so many of us go into our trips with the idea that we're taking it to improve our lives, and then when you're actually deep in the peak of the trip and you've got a whole universe inside of you suddenly you realize not just how unprepared you really were but more accurately, how fundamentally incapable of being prepared for the experience we really are)
That's the best sentence I've read all year on HN.
A friends mother took LSD in the 80s and still gets nightmare flashbacks.
Stay safe kids.
My mom’s brother went into psychosis during an acid trip and eventually schizophrenia. He killed himself when he was 24.
I think hallucinagens are fun recreationally and clearly have the potential for positive therapeutic use, but let’s not pretend that it’s always positive, especially in uncontrolled settings.
For whatever reason, negative anecdotes seem to be overwhelmingly third person, at the very least all the ones in this thread have been.
Based on the anecdotes in this thread, I'm getting the impression that when you have a really bad trip, you don't make it back to tell the story in the first person. The only people left to tell are the observers.
Are you a stock shill trying to devalue the rising psychedelic industry or something?
https://en.wikipedia.org/wiki/Louis_Wain#/media/File:Louis_w...
And that's before we even take into account the risk of mistelling that increases with second-hand information.
I've done breakthrough doses of DMT many times however. Fun fact, go look at DMT and psilocybin molecules side-by-side, they are nearly identical (https://pubchem.ncbi.nlm.nih.gov/compound/N_N-Dimethyltrypta... versus https://pubchem.ncbi.nlm.nih.gov/compound/psilocybine). The key difference being that DMT can be inhaled whereas psilocybin can't, so you can get blasted into hyperspace and be back to normal in 20 minutes. I've gotten the more basic fractals and symbols written in the sand and faces in the clouds type effects on LSD/shrooms, but a proper dose of DMT brought me to this level you describe (and probably a little past):
> unexplainable things, fractal patterns and music, and explored a Interstellar(2014)-like tesseract where I could choose any place in time to return to
(minus the choose any place in time to return, although the general concept was similar since I was experiencing hyperdimensional objects and just as you can conceive of a cube as an infinite amount of 2d sheets of paper, so too can, say, a 5D space be viewed as an infinite amount of 4dimensional manifolds stuck together)
> I re-experienced my forgotten birth and felt the pain of my circumcision
Very interested in this experience. I won't go down the rabbithole too much but I'm in the (long) process of foreskin restoration, and definitely think that strapping a newborn to a table and (mostly) irreversibly damaging their most important organ is going to send out shockwaves of suffering that last not just your own lifetime but of course like all pain continues propagating forward through our children, etc. Anyway, all that aside, I'm wondering how much reading you'd done into circumcision and its effects before taking that trip. What I'm getting at is in psychology it's considered pretty well accepted that we can falsely re-experience memories, and so just curious what your "priors" were going into the experience. In other words, had you never thought about your circumcision (except superficially), and then had this forgotten birth / re-experienced trauma of circumcision experience, or do you think your subconscious was already "loaded up" with negative attitudes towards it, and this was just a sort of visceral expression/manifestation of that? (To be clear, even if the memory itself was a false memory, the trauma itself, whether it's just the more basic "pain sensitizes you to further pain" effect that's well studied or rather the more complicated self-propagating effects of the actual feeling of complete terror and helplessness that we must have felt as a baby and carried through spacetime, is clearly not false)
Lolwut? Look, I really enjoy my penis. Ol' penie and me have been through a lot together. But it's not even in my top five list of most important organs.
Like, gun to my head, I have to live the rest if my life without one of; dick, heart, liver, kidneys, brain, or dermis; I'm sorry but the choice is pretty obvious
If I wanted to really push it, it's WAYYY down on the list. Like, the choice between losing my dick and one of my fingers; fine the finger goes. Between penis and the whole hand though? Sorry willy. Two fingers? Can stand to lose them. Three? Depends if it's the same hand. Any four fingers? Junk is back on the chopping block.
Gallbladder? Dunno what that even does, but my sister had hers out and she seems fine, so I think I would go with that. Pancreas? Yea, I would rather have a pancreas than a shlong
Not to mention that you can still reproduce without a foreskin, but if you were just a disembodied but otherwise intact dick-and-balls; I doubt your reproductive chances would be particularly high. So from an evolutionary standpoint, I would still argue that it isn't the most important organ.
https://www.theguardian.com/science/2021/mar/02/microdosing-...
The actual study is here:
It's wild that there was a part of this study in which people were told that they weren't taking a psychadelic, but they were taking a psychadelic.
The study heavily builds on self-reported belief about group membership (placebo or treatment [microdose]) for each trial day. If someone believes they are on shrooms all the time while not, and their psychological parameters improve, it's placebo. If someone produces some arbitrary pattern of on-off while actually not on anything, that's just noise for the study. That's why there's statistical significance testing.
I’m going to say few to none.
This study seems very unreliable, and I wouldn’t count out the possibility that it is junk science published to drive down stock prices of psychedelic health companies.
One one hand I'm inclined to believe the study because it confirms the placebo effect. (Which is very well established, plus the theory and the data are simple. The result is completely in concordance with the regular ineffectiveness of most low-dose not-really-psychoactive medications - meaning how SSRIs and other anti-depressants are about as effective as placebo.) On the other hand it's also possible that the study is junk, like most studies.
> How many of the participants tested that their drugs actually contained the correct amount of the correct compound?
https://elifesciences.org/articles/62878
"The inclusion criteria were: >18 years of age, good understanding of English, intention to microdose with psychedelics, previous experience with psychedelics (either micro- or macrodosing), no use of psychedelic drugs from a week before the start until the completion of the post-regime timepoint (other than the study’s microdoses), and willingness to follow the study protocol."
Of course it's still citizen science. So who knows really.
It devised a so-called self-blinding process, in which participants filled opaque capsules with drugs or a placebo. The capsules were then placed in envelopes with a QR code and shuffled, meaning researchers could later track what participants had taken, while they themselves could not.> This study used a ‘self-blinding’ citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date.
So everyone in the study presumably was interested in microdosing and, given that they would have sourced the drugs themselves, knew what they could have been taking.
Unless I’m misunderstanding. Either way, the methodology here seems really suspect to me.
> “Our study confirms the benefits of microdosing,..."
This is really horrible phrasing since normal the normal usage of the term "benefits" in this context would mean benefits relative to a placebo. In this experiments the benefits are zero since the LSD and control pills had the same effects.
One of the hallmarks of psychedelics is a (drug induced) sense of profundity and enlightenment. If you tell someone that they're about to have a life-changing experience, then you give them a drug that induces the feeling of a life-changing experience, it's likely that they'll walk away thinking they've had a life-changing experience and change their behavior accordingly.
I agree that their conclusion is borderline misleading. Traditional antidepressant studies also show a high placebo response rate, but approved SSRIs diverge from placebo in studies. Their success is largely measured by how far they diverge from the placebo groups.
If an SSRI study showed that the medications were identical to placebo yet concluded that the SSRIs had benefit, it would be soundly rejected. Yet when the same conclusion appears in a study about psychedelics, it seems to get a free pass. I think this speaks volumes about the current bias toward psychedelic medicine.
It is essentially a scam: marketing addictive, mind- and behavior-altering drugs to desperate people who don’t know any better. The drugs don’t help, they just dull emotions and make you not care.
https://elifesciences.org/articles/62878#s4-1
"A key limitation of the present study is the lack of verification of the nature, purity, and dosage of the psychedelic substance used for microdosing. Psilocybin-containing mushrooms were used by 23% of the sample, 14% used legal LSD analogues (such as 1P-LSD), whereas 62% sourced their substance from the black market, mostly LSD (61%). According to the Energy Control's drug checking service (Barcelona), LSD blotter adulteration rates were low during the period when our study was running: in both 2018 and 2019 blotters sold as LSD contained LSD only in 90% (n = 735) of tested samples [personal communication with M. Ventrua from EC, June 2020]. The exact quantity of active ingredient within a given microdose cannot be known with certainty; however, the positive relationship between dose and blind breaking (Figure 4) and that the threshold dose for psychoactivity was consistent with a recent controlled study (12 µg vs 13 µg; Bershad et al., 2019a) provide some reassurance. Nonetheless, our results should be not understood as clinical evidence, rather they are representative of ‘real life microdosing’."
Why haven't we heard more about this??
The only really noticeable effect of microdosing is at the end of the day you might notice you feel it was a really good day and you're happy. The thing is though this isn't distinguishable from someone simply having a good day and feeling happy. The data collected in this study would have essentially been irrelevant noise, based more on the aggregate of day-to-day experiences of the subjects rather than whether or not they received a placebo.
Microdosing inherently is indistinguishable from a placebo effect as far as empirical measurements go. If the participants who received a microdose were able to somehow measure their experience with a different result to those in the control group, then they weren't microdosing, they were actually tripping.
I guess that’d only be useful for yourself and not an objective measurement...
[0]: https://www.hopkinsmedicine.org/health/treatment-tests-and-t... [1]: http://www.brooklynlearningcenter.com/services/what-it-consi...
You said, no measurable effect is not the same as volunteers perception of the effect. But wouldn’t that still be a measurable effect, by the volunteers perception?
there's tons of anecdotal reports of people experiencing tangible benefits from subperceptual microdosing; this study is valuable in that it tests those hypotheses in a semi-controlled setting.
I think that since a strong placebo (e.g. a tripper feeling good as a result of thinking they're going to have some LSD) alone can produce far more profound effects on mood than actually microdosing, all this study really did is reaffirm the placebo effect's efficacy. Any changes that would have been a result of microdosing would be lost in the noise of the placebo effect on top of whatever else was going on in each participant's life at the time.
i can only read this statement one of two ways:
a) you don't think that such a difference can be measured at all, which is antithetical to the entire premise of RCTs and statistical power.
b) you don't think such a difference can be measured among microdosers because microdosing is such a small effect. but this is exactly why we need the study - how else could you know that such an effect could not be measured?
the initial hypothesis that microdosing could have an effect on mood (or some other cognitive) was not some crazy unsupported idea. it had plenty of anecdotal support, i think? some mechanistic evidence, and there are plenty of other supplements which can have non-placebo cognitive effects without noticeable bodily effects. for example, caffeine has thoroughly-demonstrated improvements on alertness and attention, even at doses where many people will not feel an increased heart rate or other physical effects.
The headline could be interpreted by some as "hey, the placebo is just as good as the real thing, losers" but this only seems likely to be true for some who are taking it, not all...
...Or am I misreading?
> A key limitation of the present study is the lack of verification of the nature, purity, and dosage of the psychedelic substance used for microdosing. Psilocybin-containing mushrooms were used by 23% of the sample, 14% used legal LSD analogues (such as 1P-LSD), whereas 62% sourced their substance from the black market, mostly LSD (61%).
Oh, and this was interesting:
> We note that according to our data the threshold LSD dose where participants guess better than random is 12 µg, see Figure 4, which is in line with the 13 µg threshold dose estimated by a recent dose controlled study
So in this group 12ug is roughly where the consciously notable effects begin (for this study population). For context, it's commonly said that "if you can feel it then it's not a microdose"; I consider ~5ug to be a microdose.
---
Anyway, I've got a lot of experience in this area because I microdosed ~4-5 ug LSD per day, every day, for about a year and a half. Also, this was from LSD liquid I made myself starting from raw crystal. So while I don't know the purity of the crystal itself, I at least knew how much of "my" crystal I was taking. (Getting a proper purity figure requires performing GC/MS - which you can only get done legally by sending a >=50 mg sample to EnergyControl in Spain, and I elected not to because I didn't want to have to sacrifice 50mg (= 500 doses) of crystal to send them)
For someone like me who is (relatively speaking) experienced with psychedelics, I can absolutely notice 5ug (it's subtle, of course, but definitely there), so note that the ~12ug detectability threshold they found in the study depends on how attuned the user is to the effects, etc. Really when most people talk about "noticing" something they don't actually "notice" it until they hit the point where they are incapable of not noticing it (for example, someone drinking for the first time will claim they feel the same 20 minutes after taking a shot, and when they finally admit that they're "drunk" they're properly drunk and not just "buzzed")
Anyway, enough rambling. Microdosing had an effect, but I took it for the same reasons (albeit smaller-scale) that I would take a full dose of LSD: increased energy, an increased "non-linearity" of thought patterns that is counterbalanced by the more traditionally stimulating effects of LSD (LSD is a Dopamine receptor D2 agonist), improved visual acuity and vibrancy of colors (well, full doses don't "improve" your visual acuity since a psychedelic dose cranks up the pattern recognition/perception transformation weights of your brain way past a functional state)
That is to say, that I wasn't microdosing to miraculously change my life or anything like that. Microdosing won't do that and the annoyingly-pro-microdosing-to-a-fault crowd really needs to get that.
While I'm rambling, I'll add that I personally have almost never taken LSD for a "spiritual transformation" or whatever you want to call it; I find psilocybin mushrooms to be far superior in that aspect. Basically, relatively speaking mushrooms cause much more "mindfuck" and for me I had the distinct sensation of feeling the shrooms taking over my brain (in a benevolent sense, or at least neutral), whereas LSD is a more visual experience and more energetic (likely due to the d2 receptor agonism I mentioned earlier as well as the general structure of LSD looking like a sort of psychedelic phenethylamine, phenthylamine itself being very amphetamine-like).
That is to say, both shrooms and LSD are very similar; the "magic" of the classical psychedelics - LSD, psilocybin, mescaline - is primarily attributable to their action at the 5-HT2A receptor (read: "serotonin subtype 2a receptor"), and that is by far the most distinctive and noticeable part of the psychedelic experience. But comparing between the psychedelics, with shrooms it takes much more "mindfuck" to get to a certain level of "visuals", and vice versa with LSD. Note I've talked to people who claim it's the other way around for them, but frankly these have always been people with limited experience and/or who don't think about psychedelics very deeply (in the analytical sense of really trying to grok them) so I personally still consider "take shrooms for the 3-6 hour mindfuck and LSD for the 8-12 hour aesthetic, energetic, kinesthetic experience" to be canon.
I've kind of accepted that I'm not going to have a coherent message with this post, but psychedelics are largely misunderstood, either by their opponents as causing "hallucinations" (no) and by the zealots as being a magical cure-all or microdosing specifically being a life-changing practice. For me, taking 3g of psilocybe cubensis mushrooms on a beach as my first real trip flipped me inside out and rewired my value structures. No longer was the (unconscious) desire for social approval vis-a-vis a prestigious/well-paying career at the top of my value structure; instead, spending a warm day on the beach with friends while wearing as little clothing as possible became what was most worthwhile and beautiful. Without trying to do so, I was analyzing my past, present and future.
You see, while I meant it when I said that psychedelics are not a cure-all, they are (or more accurately, can be) the cure for many things. One of the most well-accepted findings in psychology is that, in general, your personality is incredibly non-malleable, and tends to persist across time. Well, psychedelics are the only thing I know of that can reliably and radically change one's personality, specifically the big 5 dimension of "openness to experience".
Even an hour of sitting "outside" of your self can reveal things that sober you is incapable of noticing. And, just as once one human broke the 4 minute mile mark suddenly everybody started doing it, once you step outside of your "issue" du jour, however briefly - your neuroticism, your jealousy, your fear of emotional expression, your unconscious belief that you are incapable of love, etc - suddenly you've really seen that there's a different way of living. Not seen it in the intellectual sense but really consciously experienced it.
So when sobriety returns, barring a day or two of afterglow, you're soon largely back to your old self - and yet having experienced that alternate way, you have a chance to see yourself right now the way you'd look back on your life on your deathbed: suddenly the things you thought were the small things - a friend's smile, the contented look on your dog when you scratch them just right - were the big things all along. And the big things, the things we tell ourselves are the serious things, the adult things - we see them for the tiny, insignificant implementation details that they are.
So, psychedelics can wash away a type of sickness that most suffer from unknowingly. But they can only do so when you take enough that you cease to be capable of operating in that old mode anymore. Which means invariably there's always a period during the come-up when you realize you had no idea what you were signing up for.
But they are tools - very sharp ones - and like all very sharp tools can cause tremendous damage. One of my greatest regrets was selling two very strong tabs to someone who I had assumed knew what they were doing, and so didn't spend time giving the usual disclaimers / tutorial I'd give to clients. These were very strong tabs so it'd be something like 3-4 tabs of 100ug. I can't give as much detail as I want, (let's just say that I found much of this out from the news articles after the fact), but suffice to say that they took the tabs at night and ended up in a sort of "fugue state" (not sure what the right clinical term would be) where they stripped completely naked (a surprisingly common action of those on massive doses of psychedelics), knocked on the door of a random citizen asking for help, then started attacking them when they opened the door. As I later learned, they were ex-military and had diagnosed PTSD and god knows what else (one of the many myriad "benefits" of the war on drugs is never knowing the medical status of people who you're selling powerful drugs to unless they proactively tell you). To be clear, even on ~400ug LSD it is not normal to perform violent home invasions while in a blacked-out-like state, and there were a LOT of things that had to go wrong (PTSD + probably bad at handling psychs in general + taking them in the middle of the night + other factors I'm unaware of) for such a freak incident to occur. When you move the equivalent of 10,000 hits, statistically speaking you'll end up with one of those stories eventually.
So, don't drink the microdosing kool-aid too much - do it for fun and the experience if you want but don't pretend it's going to be a radical transformation - and understand that psychedelics can cause positive changes in a way that can [help] solve problems that are resistant to every traditional tool we have. But they can also be quite dangerous. I actually think the risk of a 'bad trip' is incredibly overblown and most people freak themselves out way too much about such things, but neither should one take a cavalier attitude.
[/unstructured ramble]
> as causing "hallucinations" (no)
I used to think that. Lately my wife and I have been doing increasingly larger shroom trips. About 10 days ago we each took 5g ("lemon tek" and relatively fresh) cubensis and after finally experiencing a touch of 'ego death' my wife's skin started glowing a deep, intense blue and she was covered in glowing, multicolored jewels. It was as if a painting of Kali came to life and was in my hands. Up until now I've seen various open and closed eye geometric patterns, distortions, trails, etc. This was a new, and frankly amazing, level for me.
As this study shows, that hype might actually explain some of the effect. People primed to think they were microdosing claimed to feel significant improvements, even when receiving placebo.
I don’t have statistics to back this up, and it could be a reflection of the privilege of my social group.
My only parent, my mother, gave me only one rule that I had to live by. I had to abide by the law, no matter what it was or if I disagreed with it. She simply just did not want me to spend my life in jail and assured me that I would feel the same way by telling me how terrible jail is (which I did).
I say this because I sympathize with your standpoint. I could have written your comment in a past life.
In short, I would ask that you empathize with the concept that one's belief might exist outside the law.
A little more to say... the variables at play here have a wide range of interpretation on a personal level. I infer from your comment that you perceive the risk to be high. I perceived my risk associated with microdosing, including the risk of being shipped to prison, to be low.
Before microdosing, I had undergone a macrodose. That macrodosing session was a positive for me. As such, the reward and exploration of a microdose was enticing enough for me to try it.
Only in some US states is possession for personal use a felony. In some it is a misdemeanor or an infraction. In some legal jurisdictions these drugs are perfectly legal and are sold at retail.
Can we do a study on whether water is wet or ice is cold next?