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LSD microdosing: a randomized, blind self-experiment (gwern.net)
182 points by gwern on Oct 17, 2013 | hide | past | web | favorite | 114 comments



I'm upvoting this, and I hate to be cranky asshole guy, but something's been buggin' me and I'm not sure how or where to provide this feedback.

Gwern's articles are, well, deep. There's usually huge wall of text with lots of allusions and footnotes. Looks like a term paper somebody would write for a college course, (only extremely well done, btw)

My problem is that I'm finding it difficult to actually consume the articles. Sure, if I had an extra hour everyday to lounge around studying the intricate details of his self-experiment with LSD, such things might interest me. But the sheer volume and technical facade of the piece works against it. At best it engages my natural inclination to nit-pick. At worst it's just boring. In either case, I'm not left with a greater understanding. Having said that, if it's something I already agree with, it does make me feel like gee, I'm really smart for feeling this way. Here's this well-researched article that agrees with me!

I freely admit to being an outlier, so take my feedback for what it's worth. I am interested, however, that my feelings validate what newspaper editors found out centuries ago: state your conclusion in the lead, then supporting evidence. Write in a pyramid fashion. That way people can review the point at their leisure, then dive down if they feel it's worthwhile. Articles for the general public should not read like mystery novels. Say what you want to say, punch them in the nose. Then make your case and impress them with how smart you are.

Since I'm playing grumpy old guy already, I'll also note that these essays are getting upvoted way quicker than it's possible to actually read the things. I'm not implying a voting ring, more like a bandwagon effect. (Same result, but without all the sinister implications)


They're hard on my attention span too, but I think the style is better than the catchy inverted pyramid of NYTimes and the like. It's a bit more like the Economist in that it builds up arguments, getting "fat" in the middle rather than a bloated digest (or even worse, a hook) at the start. I don't think his goal is to appeal to everyone, and I think that's okay.


> I'll also note that these essays are getting upvoted way quicker than it's possible to actually read the things.

Single data point: I personally upvote stuff from gwern.net pretty much immediately when I see it posted here. I've been to that site many times, read some stuff, skimmed another, and I'm sure enough that this stuff deserves an upvote that I usually upvote it first, and read later.


Fellow grumpy old guy here. Executive level summaries with the ability to drill down to points would be great.

As for voting up -- it also adds to your profile's "saved stories", so that might be a motivation too.


In the linked article the first paragraph is a summary. The next few paragraphs are a larger summary. The detailed stuff starts after both of these. Just as your third paragraph recommends.


Impressive amount of data and data reduction...but it all hinges on a 100 ug dose of LSD purchased anonymously from Silk Road?

How can the OP be sure that the 100 micrograms was pure and accurate? If you can't prove that, what good is all the math?


From a comment on the page:

""" There are a great many errors in your methodology, and I do not believe you received any of the drug in any of your doses.

First off, you have no way of knowing that what you purchased actually contained the drug. The blotter may have had none in it. Secondly, even if there was some drug, you haven no way of knowing what other chemicals were in that paper, including strychnine, and its effects after being mixed with water, on the drug. Thirdly, I'm not sure that 24 hours in a fridge is a sufficient method of extraction.

But more damaging is that the drug degrades quickly and is very sensitive to its environment. It degrades in the presence of oxygen, heat and light. A common house fridge provides all three- the door is opened at least once a day (to get your dose) letting light in. The container is open to the air which provides oxygen, and while a fridge is cool, it is does not absolutely prevent degradation of the drug due to heat. I've seen storage recommendations for this drug involving sealed, light opaque containers, kept frozen in an icebox and the admonition that this will only preserve it for a few weeks.

You provided less protection, significant dilution, questionable extraction, and stored it for months.

Basically, the conclusion from your research is this: The drug war prevents the kind of exploration of the possible positive effects of such a drug, that could be carried out by a well appointed lab. """

LSD is an incredibly volatile molecule and after months I wouldn't expect any to remain. I think this is a bigger deal than the sketchiness factor of buying drugs -- a silk road vendor selling adulterated product would be severely penalized if caught and the economics don't work out.


I've done some more research on the topic in reply to that commenter, and my conclusion is that she is full of BS, to not mince words. She has yet to reply offering any citations at all for her claims, while all the authorities and references contradict her; I give a few here: http://www.gwern.net/LSD%20microdosing#degradation


Phooey. I found that that LSD keeps very nicely without special care. I had some acid I'd kept at room temperature for a number of years in Delaware (hot, humid summers), took one tab, thought it had gone stale, and took another. Both tabs worked.


Missed that comment, and very well expressed. Thanks.


That comment doesn't seem well informed given the casual way that it references the strychnine myth, nevertheless it's true that there is uncertainty about the dose.


Regardless of strychnine, LSD remains very volatile. I wouldn't term it "uncertainty", I would term it "near total lack of certainty" given small sample size and lack of (any) proper verification that the drug was even active anymore. At the very least, he could have taken a dose to serve as this purpose after the experiment (so it would not interfere, and would provide a "later" bound)—it's fairly easy, given certain high contrast imagery, to create certain visual effects that a placebo (or degenerated drug) could not.


https://en.wikipedia.org/wiki/Lsd#Reactivity_and_degradation

"""

"LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule."[6] It is stable for indefinite time if stored as a solid salt or dissolved in water, at low temperature and protected from air and light exposure.

LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centres prone to epimerisation. The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring.[citation needed]

LSD also has enamine-type reactivity because of the electron-donating effects of the indole ring. Because of this, chlorine destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water.[6] The double bond between the 8-position and the aromatic ring, being conjugated with the indole ring, is susceptible to nucleophilic attacks by water or alcohol, especially in the presence of light. LSD often converts to "lumi-LSD", which is inactive in human beings.[6]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[71] The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25°C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37°C and up to a 40% at 45°C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA.

"""


> These studies demonstrated no significant loss in LSD concentration at 25°C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37°C and up to a 40% at 45°C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions.

Sounds about right. So even at room temperature (25°C = 77 Fahrenheit), dissolved LSD is stable over a period of months, and removing light sources improves stability even more. This is pretty poor compared to a great many molecules, but far from fatal to my self-experiment.


Were you aware of this beforehand? Did you take precautions to keep the LSD in a cool place away from light?

If it was just in your fridge for five months, I doubt there was much left at the end.


I was aware of it beforehand. After I finished photographing the package, I immediately stored it in the refrigerator under an opaque object.


The OP also wrote a very detailed study of how Silk Road works:

http://www.gwern.net/Silk%20Road#lsd-case-study

In it he mentions a potential test to verify that what you receive really is LSD:

An Ehrlich test is a reagant for indole alkaloids, a category which includes psychedelics like LSD & psilocybin. As such, it can be used as a kind of quality check.

I'd assume given the rigorous treatment I've seen so far in all his posts that he probably did this test.


The test addresses the presence of the molecule. It doesn't address the quantities present. If the doses he gave himself were smaller than he believed, even by 50%, then the fact that there's no perceptible effects isn't surprising. Given the tiny quantities that he's dealing with anyway, any slight variation of the input conditions (which he didn't account for) would make a huge difference to the output.


he probably did this test

The only difference between science and screwing around is writing it down.

If the author's goals were less lofty, I might be inclined to make this assumption, too. That said it's equally likely, given that he recorded so many other aspects of this experiment, omitting this from the record indicates that the test was not performed.


> I'd assume given the rigorous treatment I've seen so far in all his posts that he probably did this test.

If he did, he would've said so in the write-up.


Yet, still no calibration.

I admire the rigor of his work, really. It's just a nagging detail that's kind of key here.


> I'd assume given the rigorous treatment I've seen so far in all his posts that he probably did this test.

No. See the final section: http://www.gwern.net/Silk%20Road#voi-ehrlich-test If I had been able to afford more tabs, I probably would've used one (it wouldn't've confirmed the dosage or anything, but it would at least reassure me I wasn't getting an RC), but I only had 2 tabs. I needed 1 for the microdoses, and 1 to trip with, so... Between tripping and testing, it was an easy choice.


Wouldn't the test still come up positive even if it was mixed with other chemicals too?


> but it all hinges on a 100 ug dose of LSD

More than that.

> How can the OP be sure that the 100 micrograms was pure and accurate? If you can't prove that, what good is all the math?

I cannot be sure, any more than anyone getting LSD from a non-lab source (which is everyone) can be sure. All I can say is that the seller, VitaCat, was reputable; the Avengers regularly tested wares to keep sellers honest; the FBI reported high quality levels for their purchases of LSD among other drugs; the price was not too good to be true; the physical small size of the tabs meant that it had to be some highly psychoactive chemical; the trip matched reports of LSD trips very closely, and did not match many of the RC trips I've read; and so on.

> If you can't prove that, what good is all the math?

The math is there so that if I took LSD, as I highly likely did, I don't then waste the data by a screwed-up analysis.


If you just took a bigger dose at the end of tje week you would know if there was any in it or not.


There was a group of silk road users who regularly tested vendors and posted results

see: http://www.theverge.com/2013/10/14/4828448/silk-road-lsd-ave...


Yes. You can find the SR forum thread for the Avengers archived at http://www.gwern.net/docs/sr/2013-10-15-lsdavengers.maff


I also find the methodology lacking.

"This suggests the following design: a randomized dose on day 1, followed by days 2 and 3 off, then on day 4, drinking the second container; on day 7, examine the containers recording whether active/placebo and finally, starting over as day 1 of a new pair of 3-day blocks."

That means that, during the experiment, the subject can learn correlations between the test and the control ("So, I tend to go to the bathroom in the middle of the night in the test.")

If the subject has some (conscious or unconscious) prejudice for the result, he can use that information to adjust his self-reporting (again, consciously or unconsciously). For example, a subject may report a silly thought as a creative one instead of as a stupid one.

Also, given that the period of the experiment is exactly a week, I also would control for 'LSD is the first thing exactly as often as the test"


>For example, a subject may report a silly thought as a creative one instead of as a stupid one.

You would have to assume that I was subconsciously also lying in the predictions, to hide my foreknowledge, and how would I be able to precisely affect the sleep or Mnemosyne scores?

> Also, given that the period of the experiment is exactly a week, I also would control for 'LSD is the first thing exactly as often as the test"

? 3-day blocks imply a 6-day cycle, not 'exactly a week'. And I'm not sure what you mean by 'control' either.


I must have interpreted the "finally" in "on day 7, examine the containers recording whether active/placebo and finally, starting over as day 1 of a new pair of 3-day blocks."

And control: see http://thesocietypages.org/socimages/2013/01/12/what-does-it...


> And control: see http://thesocietypages.org/socimages/2013/01/12/what-does-it....

Yes, I'm aware of the statistical concept, and do controlling in a few other essays. My point was: 'control' is not an instantly obvious application. What am I controlling and how? Am I modeling it as a separate additive categorical variable? Quantitative variable? An interaction? (All different in R's formula notation, because they're different - +, *, :, and |) When you say

> I also would control for 'LSD is the first thing exactly as often as the test"

I don't even know what I would be controlling here, since I don't know what the order is supposed, what the 'test' is, and so on. You may think your suggestion is clear, but to me it's as clear as mud.


If your cycle is 7 days (which it isn't, but which I initially understood it to be), you will want to make sure that, with an experiment running for 2N weeks, you take the LSD-spiked water exactly N times on Monday and N times on Thursday, rather than relying on luck to get close to that.

One way to do that is to make 2N packages containing a spiked and a non-spiked sample, with one sample marked 'take me first', and, in N cases, have the LSD-spiked sample be that sample. Of course, if you do that, it is even more important to not inform the subject about the history of he experiment before it is over.


> If your cycle is 7 days (which it isn't, but which I initially understood it to be), you will want to make sure that, with an experiment running for 2N weeks, you take the LSD-spiked water exactly N times on Monday and N times on Thursday, rather than relying on luck to get close to that.

I see. So you were suggesting throwing in a categorical variable for the day of week and including that as a additive covariate to control for fixed-effects on days. I haven't actually run into any of my experiments depending on day of week to any important degree, but I still try to avoid 7-day blocks to make that less of an issue. It's not like there's usually an advantage to running in a weekly block, so better safe than sorry.


Given the fact that he had a null result, I don't think this criticism could possibly be valid.


Most importantly, the criticism of a _design_ is independent of the results of the experiment.

Secondly, he may have wanted a null result.


> Most importantly, the criticism of a _design_ is independent of the results of the experiment.

Flaws can go in any direction, and make a design conservative or optimistic. In this case, the identified flaw does not undermine the actual result of the experiment - though it would have undermined the opposite (hypothetical) result of positive effects.


If you design an experiment in such a way that outcome A can be explained away by "yes, but the design is flawed", while outcome B cannot, I don't think it is fair to do the experiment.


Experiments don't have to be 'fair'; your 'fairness' is not required for tests to be informative. Imagine an IQ test which spits out a binary yes/no result based on whether you're in the top 10% or not. This is a useful, meaningful test, which is 'unfair' in your naive sense. Issues of information content, discrimination, false positives and negatives - it's more complex than saying 'it is fair to do the experiment'. In this case, I got a reliable negative, rather than a less reliable positive.


Exactly. Even within a single sheet, the dose per "tab" can vary. Outside of that, even from the same vendor, the dose might vary by a factor of 5. The only remotely reliable method is to take enough to be psychoactive, then wait a week and take it again, trying to hit the point where you have threshold effects (a binary search over dosing strength). Even then you might be off on your dose guessing be 30% or more.

He may have gotten far less LSD than he believes.


> He may have gotten far less LSD than he believes.

Or more. In the absence of any reason to believe one direction, the expectation of the shift is zero...


In general, why would a vendor sell more of any drug? I'd think that getting undersold is far more common than getting free product.


That's different from saying that the layer's product can vary from tab to tab.


I also think a distinction needs to be made between Walt and Jesse's production methods.


"The claims made by psychonauts are frequently extravagant and unjustified; the tangible benefits are either unrelated to the truth of the experience (such as lessened anxiety of death)"

I don't think this is accurate. The key mediating variable for reduced anxiety is having a mystical experience, and one of the defining characteristics of the mystical experience is that it feels more real than real life. C.f. csp.org/psilocybin

"Physicalism, by contrast, could be easily falsified. If science ever established the existence of ghosts, or reincarnation, or any other phenomenon which would place the human mind (in whole or in part) outside the brain, physicalism would be dead."

I know he's just quoting Harris here, but this is BS. There is literally no known phenomena which you couldn't explain away with some as yet undiscovered materialist phenomena. C.f consciousness, spooky action at a distance, etc.

"Many years later, I have yet to have a mystical or religious or peak experience which could either convert me or leave me unmoved, and thus empirically settle the issue as to why I am an atheist - absence of experience, or reasoned belief?"

Given that 80% of people have these experiences in the lab while on psilocybin, if you are judging without having had these experiences yourself then that's just lazy. Even if you don't want to go the drug route, the vast majority of people also have chakra type experiences within the first few days of taking up meditation in a retreat setting.


> the vast majority of people also have chakra type experiences within the first few days of taking up meditation in a retreat setting

and here I sat several retreats with dagger-like pain in the knees, wandering mind, and a deep desire to somehow exit stage left unnoticed.

Meanwhile I guess everyone else was blowing open the dharma gates. Possible, but if everyone progressed as quickly in the retreat experience as you're implying, we'd soon have an enormous number of teachers (whereas the reality is that a teacher is a rarity and a student is one of the vast majority).

As for hallucinogens, they certainly provide immediate, and sometimes unwanted, entry into non-self/non-body, but as a way of life, not so sure. If you look at the great mystics of past and present, you'd be hard pressed to find one that depended on external stimuli.

Saying that, I take a journey into the woods a couple of times per year, life is short.


"If you look at the great mystics of past and present, you'd be hard pressed to find one that depended on external stimuli."

A good (albeit possibly apocryphal) example would be Jesus. His epithet was 'the anointed one', because he regularly covered his body in an oil that contained enormous amounts of cannabis, among other psychoactive ingredients. (At least a according to several linguists.)

"and here I sat several retreats with dagger-like pain in the knees, wandering mind, and a deep desire to somehow exit stage left unnoticed."

You're not going to have a mystical experience from meditation as a beginner, but it's pretty typical to start experiencing various energy phenomena after a few days. It depends what kind of meditation you're doing though.


re: Jesus and annointing himself with cannabis, I'll stand by the historically great mystics (Jesus,Buddha,...many others,Ramana Maharshi,Krishnamurti,etc.) not _needing_ anything to alter or enhance what is.

re: stages of meditation, sure, energetic experiences will come soon after starting a retreat, but in my experience, while interesting events will happen, there was a certain grind to a 5, 7, or 10 day retreat that left me feeling more bored out/raw than realized.

Don't do retreats anymore, drawn fully back into the world, for better or worse, not sure ;-)


Isn't Buddha normally depicted as being surrounded by datura flowers on his death bed? They might not have needed these things on any given day, but given that it's a path, you might need various tools from time to time to get around obstacles blocking the way. You might only use a substance once or twice in your life, but if not for that you might never have advanced any further.


If we take the sutras attributed to the Buddha as coming from one being, it would be laughable to think that this utter non-person would require anything to alter an already complete experience.

Repeating myself, but the same goes for the great mystics past & present. As to what they did prior to awakening, perhaps some did take hallucinogens, but given that none of the extant teachings suggest ingesting external substances, we can conclude that hallucinogens are non-essential to awakening.

In the west, where materialism reigns, many of us grow up spiritually bankrupt and turn to strong experience (hallucinogenic intake in my case) as a means to fill the void. Provides a much needed break from technology and rational thinking, but not convinced that this does much more than spin the wheels in place.


I think the number of teachers is much more affected by demand than supply. You can't be a teacher unless people want to pay attention to you. I had an experience that blew those gates clear off their hinges, and into the nearest ocean. But I'm not teaching, and nobody's asking. My best friend was vaguely interested for one conversation over coffee, while we were sitting around waiting for something else. Everyone other than her was far less interested than that. How many people express that they're looking for more? How many act like they know just who they are and what they're doing? The world only has attention for a relative few dalai lamas or Eckhart Tolles.


Interesting, an old friend, whom I, and a couple of established Zen teachers (Rinzai and Soto) view as hugely awakened, sat a single weekend retreat, which he left due to aforementioned pain in the knees.

Apparently he tooks loads of LSD in his late teens, enough to drop out of college, literally grab a blanket and head into the woods for 6 months (verified by mutual friends).

That's a pretty "old" school approach ;-)

In the couple of years that I knew him he routinely blew my mind with in-the-moment koans.

FWIW, a brilliant mathematician and programmer who gave up silicon valley money for a non-thinking form of employment so he could more fully contemplate the magnitude of death.

OK, sure.


"...I am dubious about the actual epistemic value of the psychedelic experience; my interest, like William James, is in what I can learn from the experience about myself and religion."

If the mystical trip is what one is shooting for 10ug doses from blotter paper purchased from silk road in one's living room is just going to give you indigestion at best. If the author is serious about exploring this experience, I recommend to the author to step outside of his comfort zone and read as much as he can about what the psycohnauts (e.g. shulgin, mckenna, RAW, leary, watts, huxley, lilly) say (w.r.t. dosages, set, setting, _tools not toys!!!_, etc.) and then experiment with larger doses. Your life probably will change profoundly, for better or worse, but there is no going back. This discussion gives a glimpse into the material: < http://deoxy.org/t_weeke1.htm >.

"And this brings us to one of the issues around psychedelics. There are a lot of wannabe experts running around who didn't take enough, because you have to take a lot -- not a LOT -- but you have to take a frightening amount to get into what it's really about. People who have taken, you know, 50 gamma of LSD or 100 gamma of LSD or two grams of mushrooms or something like that, they are not qualified to hold forth on the nature of the psychedelic experience, because those doses don't deliver it to you. What they deliver is the periphery of the psychedelic experience: accelerated thought processes, a kind of depth and richness to cognition that is unfamiliar, an ability to analyze situations from unusual perspectives, or to reach unexpected conclusions."

If you don't want to go the drug route, I've had profound mystical experiences sober with flotation tanks and kundalini yoga.

EDIT: I should also mention that I've had out of body experiences with light and sound machines (i.e. < http://www.toolsforwellness.com/light-sound-machines.html >), but I'm hesitant to recommend these as they're newer and I suspect less researched (more fringe). Alternatively, ecstatic dance is a fun sober way to reach states of ecstasy, and there's lots of it in Silicon Valley!


> If the mystical trip is what one is shooting for 10ug doses from blotter paper purchased from silk road in one's living room is just going to give you indigestion at best.

Most people do not claim even indigestion from microdosing. And I agree that one would not expect 10mcg to do anything, which is why I discussed it in the terms of trips and bought 2 tabs rather than just 1.

> If the author is serious about exploring this experience, I recommend to the author to step outside of his comfort zone and read as much as he can about what the psycohnauts (e.g. shulgin, mckenna, RAW, leary, watts, huxley, lilly) say (w.r.t. dosages, set, setting, _tools not toys!!!_, etc.) and then experiment with larger doses

What makes you think I have not read a substantial amount of material from those authors?


@Gwern I just wanted to point out that I did actually like the essay as a whole, even though it doesn't necessary come off that way when I'm only pointing out the few parts I disagree with!


There is literally no known phenomena which you couldn't explain away with some as yet undiscovered materialist phenomena.

Many people (including me) believe that consciousness can't be explained with physics.


Do you believe it could be explained eventually by future discoveries utilizing the scientific method?

This is, by the way, the major weakness with Physicalism as an ontology; the scientific method is a great methodology, but it would be foolish to say "the only things that exist are those described by science" since science is, by its very nature, incomplete and continually evolving. One could say, of course, that the only things that exist are those described by some future perfect physics, but this claim is kind of circular/meaningless.

This issue is known as Hempel's dilemma: http://en.wikipedia.org/wiki/Hempel's_dilemma


Physics can't even describe consciousness, let alone explain it. It's impossible to describe consciousness without refering to subjective experience.


I am in the same boat, although I don't know if in the future someone can explain consciousness in a better way.


Downvoter: I see you disagree - how would you define consciousness without refering to subjectve experience?


"Many people (including me) believe that consciousness can't be explained with physics."

Yeah, I was trying to make the point that materialism isn't falsifiable, though this may not have been clear.


Sorry, I missed that :)


Dear gwern:

Your scientific experiment was fatally flawed on multiple counts.

A lot of (possibly most) LSD sold today (even LSD from Silkroad, and, amazingly, even LSD from vendors favorably reviewed by The Avengers (see: selective scamming)) is, in fact,a different drug altogether. Most often, an n-benzylated phenethylamine (e.g. 25I-NBOMe). The only thing these drugs have in common with LSD is that they are potent hallucinogens, but you wouldn't notice the difference anyway on a sub-treshold dose.

Even assuming that those two tabs really did contain LSD (and dosed at 100ug, at that), "extracting" LSD from blotter by submerging it in water for 24 hours is...not known to work reliably, to put it mildly. I can tell you from anecdotal experience that this method leaves a significant amount of the substance embedded in the blotter.

Finally, putting LSD dissolved in an aqueous solution in a regular fridge is a horrible way to go about storing it. LSD must be protected from light and from changes in temperature, so a fridge doesn't work very well in this regard. Plus, dissolving LSD in a solution makes it degrade much faster, if the solution comes into contact with oxygen, since the surface area where reactions with oxygen can occur expands vastly.

It may seem harsh to say that the -vvv essay, into which you clearly put a lot of effort, is useless, as far as its "scientific"", or even informational merit is concerned. But that is the unequivocally the case. We learned something about you through this essay, but we learned nothing about LSD.

And I can't resist a little addendum - you would have done much better if you simply swallowed those two tabs, sat down in a comfy chair, put some nice music on, and tried to figure out what are those extravagant claims of psychonauts about ;)


> A lot of (possibly most) LSD sold today (even LSD from Silkroad, and, amazingly, even LSD from vendors favorably reviewed by The Avengers (see: selective scamming)) is, in fact,a different drug altogether. Most often, an n-benzylated phenethylamine (e.g. 25I-NBOMe).

Your source for these sweeping claims?

> The only thing these drugs have in common with LSD is that they are potent hallucinogens, but you wouldn't notice the difference anyway on a sub-treshold dose.

I wouldn't, no. But that doesn't explain why when I tripped on the second tab, it exactly matched what I was expecting from what I'd read about LSD trips.

> I can tell you from anecdotal experience that this method leaves a significant amount of the substance embedded in the blotter.

How exactly does that work, given that LSD is water soluble and the solution was very dilute?

> Finally, putting LSD dissolved in an aqueous solution in a regular fridge is a horrible way to go about storing it. LSD must be protected from light and from changes in temperature, so a fridge doesn't work very well in this regard. Plus, dissolving LSD in a solution makes it degrade much faster, if the solution comes into contact with oxygen, since the surface area where reactions with oxygen can occur expands vastly.

It seemed a standard approach which protects it from light and heat degradation, and there would be no 'changes in temperature' given that the tabs were stored in the refrigerator the entire time before being turned into a solution which itself was stored in a refrigerator the entire time.

> And I can't resist a little addendum - you would have done much better if you simply swallowed those two tabs, sat down in a comfy chair, put some nice music on, and tried to figure out what are those extravagant claims of psychonauts about ;)

I am amused that you think I didn't do exactly that. So, you have made these claims assuming that I did not trip or listen to music. Now that you have learned that I did, and I regard my previous opinions as still correct, are you changing any of your beliefs?


> Your source for these sweeping claims?

No source. Just information that you may for all intents and purposes call hearsay. What is your source that proves your tabs had LSD on them? Why didn't you get them lab-tested? Or at the very least reagent tested?

> How exactly does that work, given that LSD is water soluble and the solution was very dilute?

Didn't you say you took the blotter out after a day? Can you prove there was nothing in the blotter?

> It seemed a standard approach which protects it from light and heat degradation, and there would be no 'changes in temperature' given that the tabs were stored in the refrigerator the entire time before being turned into a solution which itself was stored in a refrigerator the entire time.

Were the tabs stored in an airtight container before being turned to solution? How did you account for condensation when you took them out?

I'm sorry if I unfairly doubted your LSD storage-fu. Your post, however, did not give me the impression that you knew what you were doing when you were handling the substance, and I remain unconvinced even after reading your reply.

> I am amused that you think I didn't do exactly that. So, you have made these claims assuming that I did not trip or listen to music. Now that you have learned that I did, and I regard my previous opinions as still correct, are you changing any of your beliefs?

I have not changed my beliefs, and why would I? I objected to the way you conducted your experiment, not to the fact that you did not go for a psychedelic dose. Knowing that you did go for it, changes absolutely nothing.

In fact, now that you have clarified that you ran your entire experiment with mere 1(!) tab worth of LSD (let's give the tabs the benefit of doubt), I can't help but be amazed at how quick you are to arrive at conclusions.


> No source. Just information that you may for all intents and purposes call hearsay.

So I can ignore it.

> Can you prove there was nothing in the blotter?

Umm... No? Can you prove there is not a teapot in orbit around Mercury? The LSD dissolving out is exactly what one would expect of a water-soluble substance. The burden is on you.

> Why didn't you get them lab-tested?

Because I am not rich. Send me $300 and I'll be sure to lab test any additional batches.

> Or at the very least reagent tested?

Because an Ehrlich reagant only shows the presence of indoles, and wouldn't show me what I needed to know, which was whether there was LSD, and what total dose was present.

> In fact, now that you have clarified that you ran your entire experiment with mere 1(!) tab worth of LSD (let's give the tabs the benefit of doubt), I can't help but be amazed at how quick you are to arrive at conclusions.

That's the thing about micro doses. They're, well, tiny. You only need one or two normal doses to make enough microdoses to test. That's what the power calculations were about, whether I needed one or two entire tabs.

> Were the tabs stored in an airtight container before being turned to solution?

They were shipped airtight and kept airtight until I tripped, then the remaining tab was mostly but not entirely sealed until a week later. Given that people routinely stash tabs in books and other places, I doubt that the week did it much damage.

> Your post, however, did not give me the impression that you knew what you were doing when you were handling the substance, and I remain unconvinced even after reading your reply.

Given your failure to provide any real information, despite your criticism, I'm not convinced you know what you're doing either.

> Knowing that you did go for it, changes absolutely nothing.

Really? Let me remind you what you wrote in your little supercilious comment about the fatal flaws:

> And I can't resist a little addendum - you would have done much better if you simply swallowed those two tabs, sat down in a comfy chair, put some nice music on, and tried to figure out what are those extravagant claims of psychonauts about ;)

You should have resisted, because you look like an idiot when you say that and I turned out to have done exactly that without the consequences you apparently expected.


Take heed to the last paragraph, gwern, and when you do remember "Shpongle."


An interesting analysis with a fantastic level of detail. Much of the gwern's stuff is similarly well researched - I'm a big fan! However, I can't help feeling that it's fundamentally flawed.

I understand that much of the statistical analysis done is to provide as rigorous a study as is practical, however I think in some cases it misses the point slightly. The biggest issue is that the variables that drive all the analysis are ultimately almost all perception based. I'd imagine that gwern is far more in tune with his perception of things than the average person will be (a by product of doing so many double blind tests), but ultimately he's still just a human. For me, many of the variables in the study - how well I slept, my mood, my willingness to work - vary considerably day to day anyway.

Ultimately, the study found no difference. Given that we know that LSD is very active at the right doses, the only thing that you can really take away from this is that the dose wasn't high enough. Until a study has been done which yields perceptable differences, positive or negative, you can't really draw any conclusions. It's probably also fair to assume that the dose used was likely to be smaller than stated (a by product of the black market), and so the microdoses used were correspondingly reduced.


> For me, many of the variables in the study - how well I slept, my mood, my willingness to work - vary considerably day to day anyway.

Certainly. That's why it took closer to 6 months rather than 6 days. The more variation, the more data you need.

> Ultimately, the study found no difference. Given that we know that LSD is very active at the right doses, the only thing that you can really take away from this is that the dose wasn't high enough.

No. What you can take away from this is 'while no one doubts that at 100μg and higher one gets dramatic psychedelic effects, the suggestions that at tiny doses like 10μg there are non-psychedelic genericly positive effects, may not be true'. Don't confuse your hypotheses here.


> No. What you can take away from this is 'while no one doubts that at 100μg and higher one gets dramatic psychedelic effects, the suggestions that at tiny doses like 10μg there are non-psychedelic genericly positive effects, may not be true'. Don't confuse your hypotheses here.

What?? No, you can't take that away. In fact, what GP said still makes a lot more sense. 10ug didn't work for you, thus the dose was too low. Have you tried 15? 20? 30? It would almost certainly be sub-threshold when it comes to the psychedelia (unless you are a true freak of nature), but, who knows, maybe you would get an amazing nootropic effect!

Why did you decide to abort your experiment after trying only an arbitrary dose of 10ug?


> Have you tried 15? 20? 30? It would almost certainly be sub-threshold when it comes to the psychedelia (unless you are a true freak of nature), but, who knows, maybe you would get an amazing nootropic effect!

What? Dose-response curves do not work that way. They do not look like binary circuits where at 10mcg they do absolutely nothing and then at 15mcg go to the moon. They look like curves. If 15 mcg was better than 12, then I should have observed something like a medium effect. If 20mcg was better than 12, I should have observed something like a small-medium effect. If 30mcg was best, I should have seen signs of a small effect, possibly not statistically-significant, but clear point-value shifts. I observed none of that.

> Why did you decide to abort your experiment after trying only an arbitrary dose of 10ug?

It was closer to 12mcg, I did not 'abort' the experiment but carried it out to completion exactly as I had planned, and it was not arbitrary but close to the middle of the reasonable range of 5-30mcg.


Throwaway here, for obvious reasons.

I'm aware of a double-digit participant, single-blind, randomized study of microdosing LSD. ~30 individuals. There are gaps in the survey results, but the whole thing was...intriguing.

No one is willing to take the risk of publishing, even anonymously. I won't insult your intelligence by discussing the results of such a chimera. I post only to lament the loss of scholarly freedom in our age.


> No one is willing to take the risk of publishing, even anonymously.

I find it hard to believe that such an experiment could not be written up in a way that made it impossible to guess who the participants were. In fact, I would be happy to do just that and add it to my page for you; you can find my PGP key in http://www.gwern.net/Links#contact (I am routinely contacted by people through PGP, especially post-Snowden, so your email would not stick out).


So has gwern done a psychedelic dose of LSD?

> Everything I’ve heard or read is consistent with what such experiences seem to be: the brain in a very unusual state, malfunctioning in many respects and perhaps functioning better in a few other respects.

I simply cannot take that seriously from someone who has not had a proper psychedelic trip from LSD. "You have no idea" would be a massive understatement.

Take 250ug then try and write an article about it.


> I simply cannot take that seriously from someone who has not had a proper psychedelic trip from LSD. "You have no idea" would be a massive understatement.

I thought my trip was pretty proper, and I did not see any reason afterwards to modify what I wrote in advance. I realize VitaCat's tab, while advertised as 250μg, may really have been more like 150μg, but I wouldn't call that not a 'proper psychedelic trip', and I think I do at least have some idea.


Why not? Isn't that what it is?


No. 10ug of LSD does nothing, it has no psychedelic aspect to it at all. You need 100ug+ to have a decent trip, and 200ug+ to have the kind of trip that people become religious about.

An analogy would be saying that taking a sip of a glass of beer had some sort of effect. It's like if someone said they'd never had a drink in their life but are going to see if they can reproduce some positive effects of being drunk by taking a sip of beer once a day.


This is about microdosing, not tripping. There are some claims (one recently on reddit/r/nootropics) that taking very low doses of LSD will have various positive cognitive effects. Gwern here attempts to test these claims.

If people said that taking a sip of beer had positive effects, I'd expect Gwern to test that as well.


My microdosing experiments have always left me on the depressed and anxious side of the spectrum, even with ensured quality LSD. Its not something I would repeat. That said, my personal lower threshold is around ~300-400ug, where all of the negative effects disappear, and the positive, well-observed longer-term ones remain.


300-400μg? Lower threshold?


The μ means micro, so it must be small! ;)

Taking 300μg LSD would make most people quite... uncomfortable. A normal recreational dose is 100μg, so I'm not sure how what this guy has done is in any way similar to microdosing unless he weighs about 1,000 lbs.


What I meant to express is that longterm, small 10-30ug microdoses do have an effect on me, and that effect is largely negative, but that my "sweet spot" in terms of experience is very high. Less that 300ug creates almost no observably "psychedelic" effects; its like a wasted experience with purely psychological residue. And so, following, one would think that for someone with such a high tolerance actual microdosing would have no effect at all; it does, and that effect manifests itself in a sort of unpleasant underlying low-level depression and anxiety.


Small amounts probably put your thought processes into a sort of "uncanny valley," where you can notice something is wrong, but not enough to revel in it.

It's like going outside with your zipper open, rather than with no pants at all:)

>for someone with such a high tolerance

I don't think that there's a tolerance with LSD. There's a learning curve, rather; it doesn't affect you any less, you just deal with it better.


Ultimately, as many, many, users are pointing out, this is not a controlled lab experiment despite its rigour. I applaud the author for taking initiative and I'm so happy that people are looking at drugs that are anecdotally supposed to have these positive effects, but ultimately the weaknesses inherent in testing a schedule I drug without gov't approval sink any real findings.

That being said, I find this experiment fascinating. I've taken LSD several times and intend to take it again in the future, and I've always had incredibly positive times with the drug in active doses (>150 micrograms each time). I think it's not illogical to assume that some of the positive benefits can be reached with a much smaller dose, but I agree with the author that anecdotal evidence is not convincing enough on this point.

Were this experiment to be repeated, I would like to see several key changes: - A more accurate knowledge of the EXACT dosages used. LSD, as many have pointed out, is keen to react and de-nature. A chemist making and distributing the chemicals in a more professional manner than tabs from silk road would be a huge step forward - A broader user base to sample on. Drugs don't necessarily have the same effects, at the same dosages, for different people. I believe that the author didn't receive positive effects from his dosages, but that might be the dosages or him or it might do nothing.

These nagging points hinder an otherwise very well-thought-out and conducted study.


How about doing a binary search to find the threshold dose and then investigating the effects of that?


Which is basically how serious psychonauts perform this experiment for themselves. The microdose threshold seems to be somewhere between 8ug and 30ug, depending on the person.

SWIM have tried 20ug and reported increase of energy comparable to drinking several energy drinks and have crashed pretty hard after 5 hours with increased perspiration, chills and unusual tiredness. He talked about mood elevation, heightened perception and both ability to faster enter "the zone", but also inability to stay there for a longer periods. He wanted "to have some fun" and "be more active" instead of programming.

He did not recommend it, because simply getting a better sleep and a nice breakfast have been more productive for him.


Wow that's a lot of data. I found it a little too complicated to understand. Would it be possible for someone to write a small summary? Did microdosing work for the author?


In the first section:

"I concluded that if anything, the LSD microdosing may done the opposite of what I wanted. Given that this is the opposite of almost all microdosing anecdotes and this pattern suggests placebo & expectancy effects, I strongly urge any future self-experimenters to up their methodological rigor, and especially to blind their doses."


The last part you quote is really important to understand the conclusion.

Expectancy and mood can really alter psychedelic experiences. Can't be sure for microdosing, though.

Now, how could an experiment up the methodological rigor? Maybe signing a contract where one does accept to be given microdoses of LSD randomly in a period of 5 years, and secretly spilling it on his water?


The introduction summarizes the result of his study within the first few paragraphs:

At this dosage, the anecdotes claim the usual generic spectrum of positive effects on mood, depression, ability to do work, etc.... I concluded that if anything, the LSD microdosing may done [sic] the opposite of what I wanted.


I wonder what the OP's previous experience with psychedelics is, and if it would have any effect on this sort of experiment.


I had none. Before starting the microdosing, I tripped with the second tab I had bought. It was an enjoyable and very interesting experience.


A very thorough study by gwern and an enjoyable read.

I am very glad that he has decided to conduct the study and to post the results online and hope that people won't judge him for experimenting with illegal substances for the sake of science.


With drugs like Ritalin there is a sweetspot. Some people (in the extreme case ADHD sufferers) have low levels of dopamine, and the drug can help them concentrate. Others already have high levels, and taking more hurts their study performance.

Under gwern's "temperature" theory, it seems the same should be true for this kind of LSD microdosing -- surely we should expect to see both people who benefit from additional creativity and people who already are creative enough?


Given the recent tendency for similarly potent drugs like the DOx class of psychedelic amphetamines to be falsely sold as LSD, I'm highly skeptical of an experiment whose supply comes from a random dealer online and doesn't seem to have been tested for identity or purity.


I think an important piece of information that is missing from the experiment is the name of the vendor who he purchased the tabs from. For those with an interest in high-quality LSD, Silk Road was the place to go, and certain vendors were repeatedly tested, both laboratory-wise as well as via trip-tests.

(Let me take a moment and say RIP to SR; legitimate, multilayered good-faith efforts at harm-reduction were just dramatically reduced.)

But continuing, knowing the vendor, as well as his overall reputation, would add credence to the 100ug assumption.


> I think an important piece of information that is missing from the experiment is the name of the vendor who he purchased the tabs from.

VitaCat. For all the details you could want, see http://www.gwern.net/Silk%20Road#lsd-case-study


Thanks for responding. I'm no longer skeptical!


I didn't include it in the original writeup because I thought 'well, it's not like SR sellers are household names and anyone would go "oh! VitaCat! I know that dude, he's good stuff"'. Guess I was wrong...

/edits writeup to be more explicit about the LSD source.


It's not that I know of the specific seller. I have never consumed LSD. I have never been on the SR and now obviously never will. However, you included so many details to demonstrate the rigor of your process, yet you didn't explain how you knew you were even using LSD, which seems to be far and away the single most important detail of the experiment. Now you have!


Thank you.


I've always been curious about microdosing -- would the effects not be dissimilar to certain antidepressants that work on serotonin receptors?


I see he's referenced such an example here: http://www.reddit.com/r/Drugs/comments/1ok9iy/another_lsd_mi...


Well, there is no good reason why the effects should be similar, because the mechanism of action of SSRIs and LSD is very dissimilar.


Micro-dosing is a waste of time if you're actually curious about the effects of LSD.


No it isn't. It's a waste of time if you're curious about the effects of a full dose of LSD or want a trip, but that's not the purpose here.

Did you read even the first sentence of the article?


I read the first few paragraphs. The comments turned me off to the rest.


Gwern always delivers something interesting (and dense!)


Materialism is such a narrow and limiting dogma.


In that it limits you to alternatives that at least have the possibility of being correct, yes.


That is circular reasoning.


It's particularly limiting because it refuses to see itself as a dogma.


Thank you. I missed that.


Very easy to miss, as I only posted it publicly this morning.


I was actually replying to my other comment regarding the summary. Accidentally it got posted as a separate comment and then got downvoted like hell. I wish there was a delete option in HN (alteast like a delete within 5 minutes).




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