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by apo 3687 days ago
From the study:

> A logical next step would be to carry out a placebo controlled randomised trial in which the level of therapist contact is consistent between conditions.

http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S22150366...

Depression studies are subject to well-known, powerful placebo effects, rendering this study's conclusions next to useless:

http://blogs.scientificamerican.com/cross-check/are-antidepr...

4 comments

> next to useless

No study or scientific curiosity is "next to useless". You are being intentionally antagonistic and there's no need for that. All research has to start somewhere, and this study is a significant start to this field. In no way is it or its conclusions "next to useless".

Maybe the brush was a bit broad.

However, studies interpreted more broadly than warranted can lead the unwary down deep, expensive, counterproductive dead ends. This happens all the time as the popular media get ahold stories, especially those relating to drug treatments and nutrition.

Consider the headline: "Magic mushrooms found to lift severe depression in clinical trial."

That conclusion is out of line with the way in which the experiment was conducted, especially given the high tendency for large placebo effects in such studies. Without proper controls, the conclusion that magic mushrooms lift severe depression is next to useless.

Agreed. One might say to take the conclusion with a grain of salt, but "next to useless" is being overly dismissive.
No, it is simply a statement of fact. Given that all treatments for depression produce a powerful placebo effect, any non-placebo-controlled trial tells you absolutely nothing about the effectiveness of the treatment. It's true that it does tell you if the treatment is safe, but I think it's fair to say that that information is "next to useless", as there are an almost infinite number of potential treatments. The only way to know if any of them are effective is to do a placebo-controlled trial.

Still, I think it is a plausible treatment, so hopefully there will be some better trials.

Heh, a placebo effect would make sense ...to someone that hasn't tripped. The explosion of neurotransmitters can not just be simulated or induced through coercion.

There's a chasmic divide between the effects of psilocybin and any mental state you can will consciously or subconsciously.

EDIT: unless your hypothesis is that the dissolution of the ego, lack of regard for the conventional, and overwhelming sense of identity with the cosmos are unrelated to depression. Sure a control could tell you that.

Exactly that, though, the placebo effect of interest would only be induced on people who haven't tripped.

That aside, and of course accepting that states induced by psilocybin and other substances are unobtainable by any other means, you are still nowhere near saying that these same substances can _reliably_ be used to treat depression. Furthermore, this course of treatment also needs to _reliably_ not make depression worse or trigger other types of anxiety that could trigger other medical conditions. Clearly, exactly what a aperson does under the influence of these substances can remarkably impact the results of the studies, so the techniques being used are being judged in these experiments just as much as the substances being used.

One shouldn't be dismissive of these studies, but also one should understand that the techniques used aren't the end-of-the-line in terms of potential these substances may have. on the other side of the token, we must also tread carefully. We must first do no harm!

Right! This made me laugh, the idea of a placebo with magic mushrooms.
This study is attempting to show that psilocybin is effective in treating depression, not effective in inducing a 'trip'. For patients who have never experimented with psychotropics, there may be a placebo effect when they are told they are given a psychotropic substance. While I agree that psilocybin and other similar substances can induce powerful mental states unreachable by other means, it does not follow that there exists a clinical path by which these drug-induced states can be used to treat depression in a reliable way.
So, I just mean that I find the mental imagery humorous when someone mentions a "placebo" for magic mushrooms.
Firstly, while this is nothing like proper clinical trials, there are plenty of people who have anecdotes about psychedelics helping their depression before the idea of studying this was a thing.

Secondly, if a placebo has a really high rate of success, and less side effects than currently available medication, then it could still be interesting.

And thirdly, it's going to be really, really hard to test against placebos. They're using quite strong doses to get these results, and I think it would be very hard to not realise you weren't getting the psychedelic effects unless you went into the test with literally no prior understanding of what effects the non-placebo drug would have.

But yes, a lot of research still to do. I'm rather optimistic, though.

Just because something is really hard (or impossible) to do right, doesn't mean we should do it wrong and then pretend that it was done right.
Nobody is "pretending that it was done right" with regards to placebos etc. The researchers are very clear that they think this is a small and imperfect study that will hopefully pave the way for further research in the area.
Then what did you mean by your third point? How does the study being hard to do refute the OP's statement that studies without a placebo are next to useless?
Hey,

So, firstly, I'm not qualified in science, medicine or research, and as such I'm completely open to being wrong in anything I said/will say. (But I have been following this area, and these specific researchers, with great interest.)

Secondly, since they released their results a couple of days ago I haven't yet read the entire paper, just highlights from mainstream press. I'll be reading the full paper over the weekend if not today, in case you're interested you can find it at http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S22150366...

Now as to my uneducated thoughts on the matter:

1) Maybe they will figure out a good way to do placebo controls. My mother has never tried any drugs other than weed, which was ~40 years ago in university. She swears that the first time she did it, she witnessed a third arm grow out of her body, but also acknowledges that weed doesn't have such effects. Maybe she actually smoked something other than weed, but that long ago I suspect it was just a very strong placebo. There are many, many anecdotes of for example people drinking non-alcoholic beer and seeming to become drunk, or smoking inactive things like tea leaves and thinking they are high. So perhaps, at least for drug-naieve people (i.e. those who don't already know what psilocybin effects feel like) they might not be able to tell the difference between a placebo and the real thing.

2) Given the background of the people in this trial, who have all failed to see improvement in their depression after multiple attempts, even if psilocybin was helping them only by way of placebo... wouldn't that be great in itself? These people who showed improvements had all tried at least two different types of currently-approved anti-depressants, I suspect most/all had tried therapy, etc. (Will have the exact details once I've read the full report, but one line I saw was that one of them had made 11 failed attempts to get rid of it before.) Given psilocybin made a big difference compared to every other option available, it makes me think that this being a placebo is less likely, given all of their previous attempts didn't work at placeboing (is that a word?) them out of depression.

3) If the success rate seen in this admitedly very small trial were to scale up, my gut reaction would be... cares whether it might be a placebo? I read quite recently that Pfizer tried running trials to see if viagra could increase the sex drive of women (this was shortly after they discovered it's now-used benefits for men) and abandoned them because 85% of the women on the placebo reported positive results, so they couldn't draw any data about actual non-placebo effects. Psilocybin is very low on a scale of risk of negative effects, especially when used in such conditions with experts on hand as trip sitters, if it cures $bigpercentage of people with depression who weren't getting cured by SSRIs or anything else, then I say who gives a flying fuck whether it might be caused by the placebo effect, if it works, use it.

4) Previous anecdotal experience. There are many stories of people finding either temporary, or in some cases even permanent, relief from their depression after using psychedelics (not just psylocibin). I'd hazard a guess that these are less likely to be caused by placebos, since these are people who used the drug without any expectation, i.e. without anyone saying "maybe this will cure your depression".

TLDR: Maybe they can figure out a way to do placebo controlled studies, and in my opinion even if they can't it's not neccessarily the end of the road for this research. Another disclaimer is that it's early in the morning and I now need to go do other stuff so I haven't proof-read this comment. Nor have I had my first cigarette of the day. If you get notified of HN replies, and would be interested to see if I have any different thoughts once I've read the study, I'd be happy to comment here again when I get round to doing so.

I wonder why no one studies the placebo effect. If it was understood better, we could perhaps factor out the effect for cases where it would be difficult to administer a believable placebo (as in the case here).