• Due to ongoing issues caused by Search, it has been temporarily disabled
  • Please excuse the mess, we're moving the furniture and restructuring the forum categories
  • You may need to edit your signatures.

    When we moved to Xenfora some of the signature options didn't come over. In the old software signatures were limited by a character limit, on Xenfora there are more options and there is a character number and number of lines limit. I've set maximum number of lines to 4 and unlimited characters.

The Placebo Effect

If that’s what arthwollipot meant, then certainly I agree with him, and with you. But that's a somewhat odd way of putting it, then. …I mean, take the paranormal, that I referred to earlier:

Let’s say, hypothetically, that, crazy as it sounds, one of those nutjobs that used to come up on the earlier JREF threads, claiming they could read your mind, and divine the numbers you’ve thought of continents away from them, is indeed able to convincingly support this claim of theirs of the paranormal. Or maybe they do that in a full-on lab study, not just here, online. Point is, let's assume they do it. ...Well now, first of all, that only demonstrates that some kinds of telepathy sometimes work, not that every kind of telepathy therefore works; and it most certainly does not indicate that every claim of telepathy is therefore true. Second of all, it is a demonstration only of telepathy, and not of other kinds of paranormal claims like, I don’t know, dowsing, and prophesying future events, and speaking with the dead, and recollection of “past life” memories from long ago. But despite that, it wouldn’t really make sense to therefore assert that reports that this experiment demonstrates the paranormal are wrong. It does indeed prove the paranormal, and it would certainly merit the million dollars, had that still been on offer. Right?

Yes. I forgot to reply to this post, but my point is that if a study demonstrates strong placebo, that's extremely interesting. I think I've been pretty clear about that upthread!

However, it shouldn't be reported as "explaining the placebo effect" because we know that it doesn't explain most of the placebo effect. Strong placebo may be the mechanism behind the placebo effect some of the time, but it's certainly not most of the time, and that's an important fact that should be made clear.

I believe both that to the extent that strong placebo exists as a real effect, we should be very interested in that and it should be included in our understanding of the placebo effect and that it shouldn't be reported as though it were the only thing causing the placebo effect.

Like I said, to me the really important thing, that I wanted to be clear about, is that this experiment does seem, so very unexpectedly, to indicate that expectations can drive physiological relief for causes that are not themselves psychosomatic in nature.

Yes, I agree. I still find it weird that both the podcaster and Arth's response to this paper are related to the way it's being reported in the news rather than how it impacts on our understanding of the placebo effect. The latter seems much more interesting to me, and is more related to the subject of this thread.
 
Hello folks. This was a long read when I should probably have been working!

I don't know if this is useful or interesting to anyone, but my views on the Chen et al paper are that it's an interesting piece of research. It's cool that they were able to condition the mice to show fewer nocifensive behaviours with the hot chamber floors. It's cool that they were able to then block that effect with naloxone, which shows that the change in nocifensive behaviour is probably caused by endorphins. It's a really nice demonstration of classical conditioning.

The suggestion from the paper seems to be that the mice were conditioned to release endorphins in response to which chamber they were in (prompted by the visual cues which were included in each chamber, which the paper talks about). I'm not sure that is well supported by the data? The conditioned stimulus may have just been the hot floor itself?

This is briefly addressed in the paper, where it says that in one of the tests the mice were prevented from moving between the chambers when the hot floor was switched on, and in this case they saw no difference in nocifensive between the two chambers. I don't think it was clear whether 'no difference' meant that conditioned mice in both chambers showed reduced nocifensive behaviour, or whether it meant that conditioned mice in both chambers showed the same behaviours as unconditioned mice? I assume the former, which would suggest that the stimulus was hot floor, not the decor.

But overall, to my non-expert reading, it's an interesting piece of research on classical conditioning.

To the extent I have a problem, it's just around the characterisation of this paper as "finally explaining the placebo effect". Classical conditioning will likely account for some of the effect observed in the placebo arms of some trials (alongside a bunch of other things), but I'm unpersuaded that we can reasonably say "we finally know how the placebo effect relieves pain", on the basis of this work.

On the other hand, I could be wrong about all of that. I'm not an epidemiologist, I'm just a software engineer.

There are also a lot of conversations about what "the placebo effect" is, and a lot of competing definitions. Over the years of reading the primary literature on the placebo effect, these are the working definitions I've consolidated around.

Placebo response: Any effect measured in the control arm of a clinical trial, which is not a response to the active treatment (because the control arm doesn't get the active treatment, but gets everything else). This would include pretty much any non-specific effect, including things like regression to the mean, natural history of the disease, unrecorded parallel interventions, reactivity, mistakes, etc -- anything we haven't otherwise controlled for in other groups.

Placebo effect: Any effect measured in the control arm of a clinical trial, as above, minus effects which also appear in a no treatment arm. So this is a narrower group of non-specific effects, since regression will happen anyway, natural history will happen anyway, (some?) parallel interventions happen anyway, etc. These effects seemingly brought on by the administration of the placebo - so subject expectancy effects, social desirability bias, classical conditioning, etc. Stuff the no treatment folks won't see, but is still not the active treatment effect (because you still didn't get the active treatment).

'True' or 'pure' placebo effect: Any effect measured in the control arm of a clinical trial, which cannot be otherwise accounted for. I don't especially like these terms but I don't know another and it's the one that some people use. So if we were to design some amazing mega-study, and we can somehow measure every possible variable - we measure regression, we measure spontaneous improvement, we measure the reactivity, we measure the conditioning - and we account for all of that. And somehow there is still some effect, where giving someone fake medicine still causes a measurable improvement - that would be the "true" placebo effect, the mind-over-matter effect.

(My contention is that the 'true' placebo effect does not exist. If we were somehow able to measure every variable then placebo bucket would be empty. It's entirely possible I'm wrong about this.)

However, for the majority of clinical research, we only have "placebo response" data. We don't even have "placebo effect' data (to the above definition) because most of the time we don't have a no treatment arm where we can independently measure regression. Because why would we? Who cares? We just want to know if the medicine works, and the placebo arm is our control.

But the error that is made (and this was pointed out by Ernst & Resch in 1995) is to equate the "placebo response" (which in many trials appears to show large effects), with the "true placebo effect". And conclude that the mind-over-matter "true" placebo effect is what prompts those large placebo responses. Most of the writing I have done around the placebo effect, is around pointing out where apparently large placebo responses can be explained by known effects, like conditioning, or bias, without needing to invoke a 'true placebo effect'.

But again. Maybe I'm wrong.
 
Does the colour of a pill really influence what kind of placebo effect you’ll experience?

tl;dr: no.

Interest in homeopathy seems to be on the wane, but maybe that’s just my bias.

While homeopathy is naked pseudoscience, it nevertheless yields occasional positive results in clinical trials. For scientists, skeptics, and those with an interest in the philosophy of science, this serves as an example of how poor trial design can lead to unreliable conclusions. Homeopathy, like acupuncture, has a habit of showing strong effects in badly designed trials, and small or no effect in well-conducted ones. If the heyday of homeopathy is over, perhaps we need a new paradigm to illustrate how weak design can mislead us?

I propose: the powerful placebo.

Over the coming months, I hope to explore some of what has been described as the crème de la crème of placebo effect research, scrutinising the biases, flaws, and weaknesses that challenge the widely accepted view of placebos as having real, powerful therapeutic effects. We will examine the primary literature to see if the work is really as compelling as some would have us believe.
 
Hello folks. This was a long read when I should probably have been working!

I don't know if this is useful or interesting to anyone, but my views on the Chen et al paper are that it's an interesting piece of research. It's cool that they were able to condition the mice to show fewer nocifensive behaviours with the hot chamber floors. It's cool that they were able to then block that effect with naloxone, which shows that the change in nocifensive behaviour is probably caused by endorphins. It's a really nice demonstration of classical conditioning.

The suggestion from the paper seems to be that the mice were conditioned to release endorphins in response to which chamber they were in (prompted by the visual cues which were included in each chamber, which the paper talks about). I'm not sure that is well supported by the data? The conditioned stimulus may have just been the hot floor itself?

This is briefly addressed in the paper, where it says that in one of the tests the mice were prevented from moving between the chambers when the hot floor was switched on, and in this case they saw no difference in nocifensive between the two chambers. I don't think it was clear whether 'no difference' meant that conditioned mice in both chambers showed reduced nocifensive behaviour, or whether it meant that conditioned mice in both chambers showed the same behaviours as unconditioned mice? I assume the former, which would suggest that the stimulus was hot floor, not the decor.

But overall, to my non-expert reading, it's an interesting piece of research on classical conditioning.

To the extent I have a problem, it's just around the characterisation of this paper as "finally explaining the placebo effect". Classical conditioning will likely account for some of the effect observed in the placebo arms of some trials (alongside a bunch of other things), but I'm unpersuaded that we can reasonably say "we finally know how the placebo effect relieves pain", on the basis of this work.

On the other hand, I could be wrong about all of that. I'm not an epidemiologist, I'm just a software engineer.

There are also a lot of conversations about what "the placebo effect" is, and a lot of competing definitions. Over the years of reading the primary literature on the placebo effect, these are the working definitions I've consolidated around.

Placebo response: Any effect measured in the control arm of a clinical trial, which is not a response to the active treatment (because the control arm doesn't get the active treatment, but gets everything else). This would include pretty much any non-specific effect, including things like regression to the mean, natural history of the disease, unrecorded parallel interventions, reactivity, mistakes, etc -- anything we haven't otherwise controlled for in other groups.

Placebo effect: Any effect measured in the control arm of a clinical trial, as above, minus effects which also appear in a no treatment arm. So this is a narrower group of non-specific effects, since regression will happen anyway, natural history will happen anyway, (some?) parallel interventions happen anyway, etc. These effects seemingly brought on by the administration of the placebo - so subject expectancy effects, social desirability bias, classical conditioning, etc. Stuff the no treatment folks won't see, but is still not the active treatment effect (because you still didn't get the active treatment).

'True' or 'pure' placebo effect: Any effect measured in the control arm of a clinical trial, which cannot be otherwise accounted for. I don't especially like these terms but I don't know another and it's the one that some people use. So if we were to design some amazing mega-study, and we can somehow measure every possible variable - we measure regression, we measure spontaneous improvement, we measure the reactivity, we measure the conditioning - and we account for all of that. And somehow there is still some effect, where giving someone fake medicine still causes a measurable improvement - that would be the "true" placebo effect, the mind-over-matter effect.

(My contention is that the 'true' placebo effect does not exist. If we were somehow able to measure every variable then placebo bucket would be empty. It's entirely possible I'm wrong about this.)

However, for the majority of clinical research, we only have "placebo response" data. We don't even have "placebo effect' data (to the above definition) because most of the time we don't have a no treatment arm where we can independently measure regression. Because why would we? Who cares? We just want to know if the medicine works, and the placebo arm is our control.

But the error that is made (and this was pointed out by Ernst & Resch in 1995) is to equate the "placebo response" (which in many trials appears to show large effects), with the "true placebo effect". And conclude that the mind-over-matter "true" placebo effect is what prompts those large placebo responses. Most of the writing I have done around the placebo effect, is around pointing out where apparently large placebo responses can be explained by known effects, like conditioning, or bias, without needing to invoke a 'true placebo effect'.

But again. Maybe I'm wrong.


That was a great post. I loved how clearly you defined and discussed the different terms and what they actually refer to. Through this thread we've kind of now become familiar with it all, including those of us who at the start of it really hadn't a clue; but for someone new to this, that would make for a great introduction to the whole placebo thing.

And your first post too. Welcome to the forum!

...Oh, and don't worry about posting here keeping you from work! You know what they say, apparently at our deathbed the one thing we never regret is that we worked too little, it's always the other things we didn't do that cause us regret. Certainly trivial incidental things like spending time with family and loved ones, but particularly the really important stuff, like posting here. Don't miss out on that!
 
I have got to watch placebo effects quite close now. For the past 40 years my wife has listened to me about what homoeopathy is, and how it works, and she is almost as convinced as I am, but she is from Austria where homoeopathy is an accepted treatment that is prescribed by doctors, and bought in serious pharmacies.

For the past two or three months my wife has suffered from symptoms of a circulatory disorder caused by many things at the same time, spanning from a botched knee operation that needed to be redone, old heart problems that may need an operation, a broken tooth, and much more that has of course caused some anxiety - to put it mildly.

Then a friend in Austria sends her a bottle of a super drug that has helped her overcome her own circulatory problems, and my wife finds that it is a bottle homoeopathic drops. Well, she takes it anyway, and immediately - and I mean immediately - she feels much better! Now she takes it all the time, but even she finds that it does not really work any more.

She also worries if she takes too much, or if it should be taken more often. I tell her that she should take it as often as she likes, because there is absolutely nothing else in it than alcohol, and the entire bottle would only cover the bottom of a jug, so I think she can’t even be tipsy from it. And if it works, it works.

However, it is very interesting to see the power of placebo at work, and how when effect has long gone, one still lives in the hope that it will work again. So I wouldn’t be surprised if another bottle will soon be ordered.

I should have invested in a homoeopathic drug factory!
 
I have got to watch placebo effects quite close now. For the past 40 years my wife has listened to me about what homoeopathy is, and how it works, and she is almost as convinced as I am, but she is from Austria where homoeopathy is an accepted treatment that is prescribed by doctors, and bought in serious pharmacies.

For the past two or three months my wife has suffered from symptoms of a circulatory disorder caused by many things at the same time, spanning from a botched knee operation that needed to be redone, old heart problems that may need an operation, a broken tooth, and much more that has of course caused some anxiety - to put it mildly.

Then a friend in Austria sends her a bottle of a super drug that has helped her overcome her own circulatory problems, and my wife finds that it is a bottle homoeopathic drops. Well, she takes it anyway, and immediately - and I mean immediately - she feels much better! Now she takes it all the time, but even she finds that it does not really work any more.

She also worries if she takes too much, or if it should be taken more often. I tell her that she should take it as often as she likes, because there is absolutely nothing else in it than alcohol, and the entire bottle would only cover the bottom of a jug, so I think she can’t even be tipsy from it. And if it works, it works.

However, it is very interesting to see the power of placebo at work, and how when effect has long gone, one still lives in the hope that it will work again. So I wouldn’t be surprised if another bottle will soon be ordered.

I should have invested in a homoeopathic drug factory!
The problem with the placebo is that even when you feel better, you are actually not better. This was shown clearly by the asthma study. People reported breathing easier after the placebo but when actual clinical measurements were taken there was no difference.

That's the danger. It can make you think you're getting better when you're actually not.
 
The problem with the placebo is that even when you feel better, you are actually not better. This was shown clearly by the asthma study. People reported breathing easier after the placebo but when actual clinical measurements were taken there was no difference.

That's the danger. It can make you think you're getting better when you're actually not.


I agree, but when the cause is part physiological, and part psychological, there is a chance that the placebo can reduce the psychological problems. In any case, as I said, the effect didn’t last long, and as far as I can determine, it never reappeared.

I have an example of nocebo with one of our friends. She got a drug prescribed by her doctor, but bad-mouthed it long before she started taking it (she swears on herbal treatments), and predictably, it was bad for her. I believe that in contrast to placebo, nocebo can actually cause real damage.
 
You live without running water?



;)


Something like that, but the main thing in running a homoeopathic factory is to get your products promoted.

And it seems that most Homoeopathic drops are alcoholic of some sort (which means longer shelf life).

Finally, I think that you also need to be somewhat dishonest to run such a factory, and that goes against very fibre in me. In short, I am not destined to be rich.
 
A couple of new articles by Mike have dropped:


 
Personally, here's a tidbit that gets me wary of placebo effect: you can separate the organism that takes the pill, from the one reporting the effect, and you still get an improvement reported. The most trivial example being at the vet. The poor dog is still as sick as, well, a dog, but the owner reports that it's much better.

Which kinda answers the question of whether when you say you're better, you're actually better, or it's just an illusion. It's an illusion.
 
Personally, here's a tidbit that gets me wary of placebo effect: you can separate the organism that takes the pill, from the one reporting the effect, and you still get an improvement reported. The most trivial example being at the vet. The poor dog is still as sick as, well, a dog, but the owner reports that it's much better.

Which kinda answers the question of whether when you say you're better, you're actually better, or it's just an illusion. It's an illusion.
That is not because placebo works on the dog, but because it works on its owner: they think the dog has improved, even when objectively, the condition has deteriorated!
Many years ago, one of our residents, Rolfe, who is a vet, reported how some dog owners treated their dog's skin disease with homoeopathy, and even though it was actually worse, the owners saw an improvement.
 
That is not because placebo works on the dog, but because it works on its owner: they think the dog has improved, even when objectively, the condition has deteriorated!
Many years ago, one of our residents, Rolfe, who is a vet, reported how some dog owners treated their dog's skin disease with homoeopathy, and even though it was actually worse, the owners saw an improvement.
It was one of the case reports on the British Veterinary Voodoo Society website, I think: http://www.vetpath.co.uk/voodoo/case4.html
 
Which kinda answers the question of whether when you say you're better, you're actually better, or it's just an illusion. It's an illusion.
That was the takeaway from the asthma study. People reported improvement, but when objective measurements were taken, there was actually no improvement at all.

And this could lead to someone not taking vital medication, because they took homeopathy and "feel better".
 
That is not because placebo works on the dog, but because it works on its owner: they think the dog has improved, even when objectively, the condition has deteriorated!
Many years ago, one of our residents, Rolfe, who is a vet, reported how some dog owners treated their dog's skin disease with homoeopathy, and even though it was actually worse, the owners saw an improvement.

Indeed my very point, my eloquent colleague. When it's about humans reporting about themselves, you get arguments to the effect that "well, if they say they feel better, who are you to say they're not better?" When we separate the being taking the placebo (the dog) and the one reporting (the human), we can clearly see that it only influences the reporting. The one taking the placebo can actually be worse, but the reporting is that it's better. No actual improvement is needed for people to report that it's going better. That was my point.
 
That was the takeaway from the asthma study. People reported improvement, but when objective measurements were taken, there was actually no improvement at all.

And this could lead to someone not taking vital medication, because they took homeopathy and "feel better".

Indeed. There was also a meta-study a decade ago, that also showed absolutely no difference between people being given a placebo, and those who were just told they're not getting medicine. But, yes, I'm with you, it's why I oppose the idea of placebo, homeopathic, herbal, holistic, acupuncture, etc, actually having an effect.
 
A deeper dive on the placebo surgery myth, and how if there is no difference in results between real surgery and placebo surgery, it means that the real surgery doesn't work, not that the placebo works just as well.

 
Back
Top Bottom