Hacker News Reader

Comment by riedel | Hacker News Reader

No expert, but I had some immediate questions when reading this. Wasn't the dose high enough to be easily distinguishable from the placebo without any experience? Why not some other drug a palcebo? Is single blind design actually advisable in such a study? Can someone enlighten me?

View on HN

Placebos in psychedelics studies are rightfully often laughed about, but if the placebo group never took LSD before, it may indeed not be obvious to them if they got the drug or not.

Also people vary on response to all pharmas. Some are simply "hardheads." [0] And this can vary with concomitant medications. So it's inportant to capture these results.

[0] not the most scientific reference but the term "hardhead" is useful here: https://www.shroomery.org/forums/showflat.php/Number/1446930...

The potency of the placebo effect with psychoactive drugs is pretty remarkable. It also illustrates an interesting effect about the cultural influence on intoxication. It's one of the more easily repeatable placebo experiments.

If you give a bunch of young adults who have never drunk alcohol some "alcohol" and then observe them, they both a) act drunk b) act drunk, according to their expectations about alcohol. (People who report that they believe alcohol makes people more social act more social, those who report that they believe it makes people withdrawn, become morose, etc.)

Another repeated finding, in both placebo and non-placebo groups, is that the alcohol takes effect before it would... take effect. People change behaviour almost immediately. I've noticed that with a drink myself; I'm feeling the drink before I possibly could have absorbed it. It also works the other way too -- a group of actually drunk people behave more sober when you've told them it was just rum-flavoured water, not actual alcohol.

I suspect the placebo effect has limited duration for those who are experienced with psychedelics. I can imagine wrongly thinking you’ve been dosed for about 90 minutes, but after that one would surely know, at least for LSD.

>People change behaviour almost immediately. I've noticed that with a drink myself; I'm feeling the drink before I possibly could have absorbed it.

I have noticed a similar thing in myself. The second I taste alcohol, it is like a switch was flipped, and I am now "drinking mode". Presumably some strong state-dependent learning. On the other hand, if I am physically dehydrated and drink a glass of water, I immediately feel better even though it must surely take several minutes for the water to start being absorbed.

> Wasn't the dose high enough to be easily distinguishable from the placebo without any experience?

This was my first thought. There’s no way that anybody would mistake 75 ug of LSD for placebo.

I'm not sure about this. I'm a big guy, I barely feel 100 ug, if I didn't know what LSD was like I could easily not notice

This was intravenous though, so I’d assume the effect to be much stronger than when taken oral.

Are you sure you have really taken 100ug? The blotters these days are very often quite a bit less, although marketed as 100ug. 100ug should be enough for most for a good trip.

The placebo here was saline (no physiological effect). Sometimes they give amphetamines as a placebo so the control group also feel that something is different. But I’d expect that to affect RL hyperparameters too.

I'd think there were two ways to produce this.

The first would be to not disclose the dose. If you don't know the dose, you might just assume it is a low dose and you aren't getting effects. This is especially easy to pull off since a lot of folks know about microdosing - which usually has the goal of not-too-much-hallucination.

Second, you can get folks new to LSD in combination with the above.

I'd think that the issue with giving another drug is that we wouldn't know how that drug is going to affect the outcome. You still need the baseline of sober folks to compare to, and given them a fake dose means that the ones that will have the placebo effect, will.

If you have any hallucinations at all, you're not microdosing. Microdosing is right before the tipping point of recognizing you took something at all. It should be recognizable from long-term effects, not immediately.

I wonder if there is more data about this.

A while ago I've microdosed 1 to 2g of fresh truffles(which should not induce a trip), a few days/weeks after a real trip, and I had some hallucinations, which should not have happened

IDK, is it possible that a microdose could trigger some kind of a release of a previous buildup of some hallucinogens?

from lots of experience, yes it can

Doses seem to accumulate, that’s why you need days off, too, and they recommend not to mix macro and micro doses. I’ve read somewhere that after a big dose you should wait ~1 month for the effects to wean.

Micro dosing (as the name suggests) is more about the input dose, than the output results

Not really, it is about achieving some effect with a specific dose. The effect is about some improvements in your life without tripping. If you're tripping, you're not microdosing.

I think this would be an issue in any study. I assume the purpose of a double blind is not to convince those in the treatment group they have taken nothing — it’s to convince those in the placebo group they’ve taken something, and then measure that placebo effect.

75ug would definitely be 'noticeable' if you took it sublingual. But this was an IV so I wouldnt know how much dilution there would be before passing the blood brain barrier. My best guess is that it would lower effective dose and how strong thr initial onset was.

Almost all drugs show higher potency when administered intravenously...

No, IV 'only' has 100% bioavailability. This does not reflect potency.

Reply on news.ycombinator.com