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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.




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