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The Placebo Effect

I haven't watched it yet, but I'm willing to bet that it's not controlling the placebo effect, it's controlling the subjective perception of pain.

I'm also willing to bet that Mike Hall is going to talk about this on the show, because I'm going to send it to him after I have watched it.
 
Quote from the referenced link: " an attempted replication in 2011 yielded no significant differences between the informed and control groups."

Next you'll be telling us that the Hawthorne Effect isn't real either!

Oh. Wait: Hawthorne Effect Definition: How It Works and Is It Real

It used be one of my favourite "explainers".

:(

As soon as you hit the fact that it couldn't be replicated then it should be thrown in the circular filing cabinet/trash-can icon.
 
I haven't watched it yet, but I'm willing to bet that it's not controlling the placebo effect, it's controlling the subjective perception of pain.

I'm also willing to bet that Mike Hall is going to talk about this on the show, because I'm going to send it to him after I have watched it.


You should watch it before you make any bets!
The study looked at neural activity in the brains of mice.
Neural circuit basis of placebo pain relief (Nature, July 24, 2024)
 
It's not about "controlling the subjective (!) perception of pain."
The mice aren't asked to fill out a questionnaire.
 
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It's not about "controlling the subjective (!) perception of pain."
The mice aren't asked to fill out a questionnaire.


Perhaps you’ll also tell me that the mice are not told when they are given a sham treatment?

Joke aside, how would you describe the this experiment?
 
There are non-pain associated regions of mice brains that can mediate behaviour associated with pain.
 
Yes, that seems to be the point.


Perhaps you’ll also tell me that the mice are not told when they are given a sham treatment?
Joke aside, how would you describe the this experiment?


I posted more than a video.
 
Then you should be able to tell me what makes it sound to you as if it is about "controlling the subjective (!) perception of pain":
Placebo effects are striking demonstrations of mind-body interactions 1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain, a phenomenon known as placebo analgesia 3–6. However, despite the strength of placebo effects and their impact on everyday human experience and failure of clinical trials for new therapeutics 7, the neural circuit basis of placebo effects has remained elusive. Here, we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACC→Pn), a pre-cerebellar nucleus with no established function in pain. We created a behavioral assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACC→Pn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACC→Pn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACC→Pn neurons during pain relief expectation, providing cellular-level evidence of a role for the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.


I don't disagree with you when you say that it is about (hypothetically, potentially) "controlling the sense of pain," but that's not what arthwollipot said, and that is not what the study itself was about. They just think that their "findings (!) open the possibility (!) of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain," but not even that sounds subjective to me.

ETA: You will get a better idea of the whole thing if you watch the video (11 min.) or maybe just read the transcript:
0:00 Placebo Effect in a nutshell
1:05 Placebo and nocebo
1:40 History of placebo
2:30 So many studies
3:20 Neural pathways and previous discoveries
4:30 Animals also feel placebo
5:30 New study using mice
6:55 Brain pathway discoveries
8:10 Optogenetics to confirm this
9:20 Why this matters
 
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I still haven't watched it. Does he mention any studies out of Harvard? Ted Kapchuk perhaps?

If so, that casts serious doubt on any conclusions.
 
My initial look at the paper has not thrown up a lot of red flags, though I find it interesting that a lot of people who seem to be doing research on placebo effects appear to be Chinese.

One co-author is from Harvard, but I can't see any obvious links to the thoroughly discredited acupuncturist Ted Kapchuk, so no red flags there either.
 
Here we go. Mike Hall has spoken about the July paper on the podcast, and now he has written it up. Good work Mike.

Overly simplistic headlines muddy the water around placebo effects and mislead the public

Science communication is often about relating complex ideas in a clear and concise way. Unfortunately, the discourse around the placebo effect is anything but. The term ‘placebo effect’ is often used in casual conversation, popular media, and even academia as if it represents a single, well-understood phenomenon. In reality, ‘the’ placebo effect is a convoluted mess of unrelated effects that confound clinical trials.

For example, the National Institutes of Health in the US says the placebo effect works by ‘turning on the body’s natural mechanisms for helping us feel better.’ This statement is a gross oversimplification. Some placebo responses may be due to triggering the release of dopamine or endorphins, but not every placebo response can be chalked up to these mechanisms.

...

So when headlines appear claiming ‘We may finally know how the placebo effect relieves pain’ (New Scientist, 24 July 2024), we have good reason to be skeptical. There is no singular placebo effect, and no singular mechanism by which it modifies pain. Conditioning, bias, and mood can all influence reported pain to varying extents, and all are part of the placebo response. At best this discovery, whatever it is, may explain some parts of some placebo effects, but can we really say, ‘we finally know’?
 
Poor work, arthwollipot.
You quote from the introduction to the article instead of from what the article is actually about, i.e."What happened in the study".
That's a weird place to stop. Did you even read the rest of the article, which is about the mouse study that I first referred to in my post about this video about it:
Major Breakthrough! Controlling Placebo Effect Using Brain Stimulation
(Anton Petrov on YouTube, July 30, 2024 - 12:32 min.)
What Mike Hall seems to dislike about the new study is that it seems to actually avoid the pitfalls of many earlier studies, i.e. the "convoluted mess of unrelated effects that confound clinical trials."

The interesting question is: Is there such a thing as actual pain relief in the body's (including the brain's) response to pain due to expectations? And the new study appears to confirm that, yes, there is. And it doesn't stop there. It also pinpoints what appears to be the neurological response that causes the pain relief.
The study manages to eliminate two of the biggest confounding factors:
1) from the participants who don't want to disappoint the doctors/researchers who appear to be keen on relieving the pain of their patients/test subjects.
2) from the doctors/researchers who would like to see their treatment/test show a positive result.
And "regression to the mean" and "parallel interventions" also don't seem to have been involved.

If there is actual pain relief, it wouldn't be surprising if it somehow involves endorphins. And this is what the mouse experiment appears to show to be the case. In Mike Hall's words:
This strongly suggests that the pain relief observed in the previous experiment was the result of the release of endorphins. Endorphins that, in the second experiment, are prevented from working by the naloxone.

Notice his argument for dismissing the study:
While this study is fascinating, it is far from a definitive (!) explanation of the placebo effect, or even how placebo effects mediate pain. It is a clear demonstration of classical, or Pavlovian, conditioning. Classical conditioning probably does account for some (!) of the placebo effects seen in some studies but many placebo effects, even for pain, have nothing at all to do with endorphins, naloxone, or conditioning.


Let's just say that what it has discovered is "classical, or Pavlovian, conditioning. Yes, OK, and so what?! If "classical conditioning probably does account for some of the placebo effects seen in some studies," so be it. But notice how he continues: "but many placebo effects, even for pain, have nothing at all to do with endorphins, naloxone, or conditioning"
And that's true: Many placebo effects are nothing but confounding factors, but the point here is that those confounding factors have been eliminated in this study as they should be. The new study is indeed less complicated by having eliminated confounding factors that are nothing but reporting errors, and Mike Hall is almost offended by this instead of praising it.

It sounds as if Mike Hall would very much like his old confounding factors to return, so he can continue to stress the complexity of the whole thing:
Either way, headlines claiming ‘researchers explain how the placebo effect works’ are not only reductive but imply a singular mechanism where none exists. Much of the public confusion surrounding the placebo effect is rooted in this persistent oversimplification, which glosses over what is a complex set of phenomena.
The conditioning observed in these mice is a specific mechanism that might contribute to some placebo responses, particularly those involving learned associations. However, it is just one part of a much larger, more intricate picture that includes other effects like regression to the mean, reporting biases, parallel interventions, and so on.


The interesting question remains: Is there such a thing as actual pain relief produced by the body? And the study appears to show that there is. But the discovery of endorphins is by no means a new discovery. The new discovery is 1) that it appears to influenced by conditioning, and 2) the part of the brain that produces the pain relief (possibly by means of increasing the level of endorphins) has been located.

What Mike Hall describes as "reductive" seems to be the actual strength of the new study. A study design that simplifies things has often accomplished (scientific) wonders:
https://astrocamp.org/blog/gravity-experiment/Gravity Falling Experiment: Feather in a Vacuum!
Removing the effect of endorphins from the mouse experiment corresponds to removing gravity from the feather-in-a-vacuum experiment: 'Look, the feather doesn't fall at all!' All it shows is that the apparent pain relief has to do with the production of endorphins, which is no surprise but nevertheless an accomplishment.

Whether the whole thing works in a similar way in people as it appears to do in mice remains to be seen.
And it it is not as if we don't already have artificial endorphins. As Mike Hall puts it:
"I would add that a single shot of morphine will offer more pain relief than endorphins are ever likely to manage alone."
 
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I see you have missed the entire point of the article. Yes, I read it. I also listened to Mike's original analysis on the podcast. Did you?

Look at what the study says. Now look at the headline of, say, the New Scientist article, or Petrov's video. Heck, just search YouTube for the term "placebo effect" and you will find plenty more examples.

The study does not say that we have found out "how the placebo effect works", yet that is exactly how the articles and the YouTubes are presenting it. The study captured one mechanism of pain mitigation - classical conditioning causing the release of endorphins. What is referred to as "The placebo effect" is so much more than just that. But the media and the headlines make it out to be the ultimate piece of a puzzle that has now been solved, and resolved the entire question.

A recurring theme of Mike's ongoing analysis of the placebo effect, and in fact of the entire podcast, is how the media misrepresents science, and how when you get into it, the studies rarely say what the headlines say they say. It's irresponsible journalism and perpetuates misinformation.

It's a fascinating study, really, but it is far from definitively explaining how the placebo effect works.
 
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No, I haven't listened to any podcast. Why would I? What are the important points it tells us about that the article does not mention? If it's relevant, you should tell us.
And if you read the whole thing, why didn't you comment on the part of the article that was actually relevant instead of the part of it that was a complaint about headlines?

The article isn't mainly about hyperbolic headlines. That's what the introduction to the article is about. The article itself is about the mouse study.

The problem with Mike Hall's article is the bias due to his "ongoing analysis of the placebo effect," which he (and you, too) seems to think is everything that is somehow supposed to be or has been interpreted as being part of the placebo effect, including all the confounding factors that are entirely different phenomena, such as "experimenter bias," which is obviously different from the object to be studied. Otherwise, it wouldn't be confounding.

This is also why my post distinguished between all the things that have erroneously been construed as part of the object to be studied, i.e. pain relief produced by the body (and brain) itself unlike whatever may have been interpreted as having been a part of the object but wasn't actually, i.e. "regression to the mean, experimenter bias, parallel interventions, classical conditioning, and more," except that conditioning may actually be an integral part of pain relief and not at all confounding.

Mike Hall seems to want to consider the object to be studied to be the whole shebang of pain relief produced by the body and all the confounding factors, whereas the new study eliminates those confounding factors. This has nothing at all to do with being reductive like the headlines, a theme that he returns to by the end of the article for some reason.

You repeat Mike Hall's idea that the new study is "fascinating," so why don't you tell us about that? What makes the study fascinating?
 
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The article isn't mainly about hyperbolic headlines. That's what the introduction to the article is about. The article itself is about the mouse study.
See what I mean? Missing the point.

The article is about media interpretation of scientific literature. You will notice that Mike has no problem with what the study concludes. He is not disputing it. He is not questioning it. He is reporting it accurately. But read this again:

Overly simplistic headlines muddy the water around placebo effects and mislead the public

The headline says what the article is about. The article is about overly simplistic headlines, and how they muddy the water around placebo effects and mislead the public.

The article is explicitly and directly about how the media misrepresents scientific papers for sensational headlines. That's what it's about. The mouse study happens to be a convenient recent example of that.

Mike's entire thesis regarding the placebo effect (that he has developed through years of reporting on the podcast, and which you can follow through all of his articles that I have linked to here on the forum) is that due to poor science communication and sensationalist headlines, the public at large has a vastly exaggerated idea of what the placebo effect is capable of. This article is another piece of that thesis.
 
"public at large" Id say many in the medical professions also have vastly exaggerated ideas of what the placebo effect is capable of.
 
It's near-universal, as we have seen in this thread.

Have we? I just reread the thread. There's a near consensus that the strong placebo effect doesn't exist. There's some discussion of whether or not the weak placebo effect is caused by a real effect or just confounding factors.

I don't think that we have seen in this thread "vastly exaggerated ideas of what the placebo effect is capable of", certainly not near-universally.
 
See what I mean? Missing the point.

The article is about media interpretation of scientific literature. You will notice that Mike has no problem with what the study concludes. He is not disputing it. He is not questioning it. He is reporting it accurately. But read this again:

Overly simplistic headlines muddy the water around placebo effects and mislead the public

The headline says what the article is about. The article is about overly simplistic headlines, and how they muddy the water around placebo effects and mislead the public.


Arthwollipot, you really need to read that article. It's not enough to read the headline!
As I already told you, Mike Hall writes a too-long introduction to his article about a particular sturdy. The introduction is about headlines. The article isn't. It doesn't make it any better that he then gives the article a misleading headline. His reason for doing so only appears after the introduction:
What happened in the study This particular headline was in reference to a recent study published in Nature titled ‘Neural Circuit Basis of Placebo Pain Relief’.
Overly simplistic headlines muddy the water around placebo effects and mislead the public (TheSkeptic, Aug 27, 2024)


See?! He actually says so explicitly even though he himself has a peculiar and confusing headline for his own article! It would have made it clearer for you if he hadn't come up with the misleading introduction + misleading headline, obviously. It is particularly dumb to come up with a misleading headline for an article where he complains about .... headlines!

The article is explicitly and directly about how the media misrepresents scientific papers for sensational headlines. That's what it's about. The mouse study happens to be a convenient recent example of that.

Mike's entire thesis regarding the placebo effect (that he has developed through years of reporting on the podcast, and which you can follow through all of his articles that I have linked to here on the forum) is that due to poor science communication and sensationalist headlines, the public at large has a vastly exaggerated idea of what the placebo effect is capable of. This article is another piece of that thesis.


And yet, that is not what he writes about in the article! He is upset because the authors of the new study claim to have found out that there is an actual placebo effect that is independent of confounding factors, actual pain relief. It contradicts his own idea of placebo, so he wants to diminish the new study with his introduction about headlines:
The problem is that we use the same term, ‘the placebo effect’ to describe a wide array of phenomena, when the reality is that there is no singular effect. What we have instead is a morass of non-specific, inconsistent effects that confound clinical trials so perniciously they are often mistaken for clinical effects in their own right. They vary enormously depending on the context, and can include regression to the mean, experimenter bias, parallel interventions, classical conditioning, and more.
(...)
it is just one part of a much larger, more intricate picture that includes other effects like regression to the mean, reporting biases, parallel interventions, and so on.
regression to the mean ≠ pain relief
reporting biases ≠ pain relief
parallel interventions ≠ pain relief

All three things are aspects of the science of the placebo effect that, but they aren't aspects of any real pain relief. And he doesn't point to any relevance of any of these confounding effects in the new study!!!

Why won't you tell us why you and Mike Hall think that the new study is fascinating?
 
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Arthwollipot, you really need to read that article. It's not enough to read the headline!
Some of the article is simply reporting the methods and results of the study, which anybody can read by just looking at the study itself. I did not feel the need to quote that part of Mike's article, because that's not the point of the article.
 
I haven't watched it yet, but I'm willing to bet that it's not controlling the placebo effect, it's controlling the subjective perception of pain.

I'm also willing to bet that Mike Hall is going to talk about this on the show, because I'm going to send it to him after I have watched it.

I still haven't watched it. Does he mention any studies out of Harvard? Ted Kapchuk perhaps?

If so, that casts serious doubt on any conclusions.

My initial look at the paper has not thrown up a lot of red flags, though I find it interesting that a lot of people who seem to be doing research on placebo effects appear to be Chinese.

One co-author is from Harvard, but I can't see any obvious links to the thoroughly discredited acupuncturist Ted Kapchuk, so no red flags there either.

Has your view changed since you wrote the above posts? If so, how?
 
Has your view changed since you wrote the above posts? If so, how?
Yes. It's clear that the paper is not about controlling the subjective perception of pain, it's about classical conditioning being able to stimulate the release of endorphins. My initial suspicion was incorrect.

And it also appears to have little to do with discredited acupuncturist Ted Kapchuk, so my suspicion there was also incorect.
 
Yes. It's clear that the paper is not about controlling the subjective perception of pain, it's about classical conditioning being able to stimulate the release of endorphins. My initial suspicion was incorrect.

And it also appears to have little to do with discredited acupuncturist Ted Kapchuk, so my suspicion there was also incorect.

Thanks. I very much appreciate this response.

I'm not really clear on what the paper says, but do you think it should shift our credence in the idea that at least sometimes placebo effects related to pain are at least partially due to real physiological effects (such as increased release of endorphins)? Or is that just completely orthogonal to what was being studied?
 
Look at what the study says. Now look at the headline of, say, the New Scientist article, or Petrov's video. Heck, just search YouTube for the term "placebo effect" and you will find plenty more examples.

The study does not say that we have found out "how the placebo effect works", yet that is exactly how the articles and the YouTubes are presenting it...

Here's what the study actually says,
Neural circuit basis of placebo pain relief
Placebo effects are notable demonstrations of mind–body interactions. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain—a phenomenon known as placebo analgesia. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex... These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.

You describe articles saying eg. ‘We may finally know how the placebo effect relieves pain’ (New Scientist, 24 July 2024) as irresponsible journalism. Yet this is exactly what the study itself is claiming.

Of course the proper headline would be 'Experiment that hasn't been reproduced makes claim that you should ignore until it is (multiple times)", because you can never be too skeptical - and no responsible journalist would presume to have the skills to interpret something they themselves are not an expert on (which is why if I was in charge of New Scientist it would just consist of the editorial and page upon page of ads, with no articles).

As for YouTube, you know any idiot can create videos and put them up there, right? I'd say any that manage to get it this right are a welcome exception to the usual dross.

But hey, let's excoriate the ones who are trying to get it right, and treat them just like the nutcases and trolls spreading misinformation to boost their egos. Because we skeptics have our own egos to boost...
 
I'm not really clear on what the paper says, but do you think it should shift our credence in the idea that at least sometimes placebo effects related to pain are at least partially due to real physiological effects (such as increased release of endorphins)? Or is that just completely orthogonal to what was being studied?
No, as Roger points out below, this is pretty much what the paper concludes. Classical conditioning can produce an endorphin response in the absence of actual pain. The fallacy that is being reported is that this is the entire definition of the placebo effect. It isn't.

You describe articles saying eg. ‘We may finally know how the placebo effect relieves pain’ (New Scientist, 24 July 2024) as irresponsible journalism. Yet this is exactly what the study itself is claiming.
The paper concludes that they have documented a mechanism for an effect that has previously been assumed to be placebo. But by documenting it, it is no longer placebo. There is an actual mechanism involved beyond "mind over matter" which is what the public at large believes the placebo effect is, thanks to people like Ted Kapchuk and others who promote this belief.
 
Some of the article is simply reporting the methods and results of the study, which anybody can read by just looking at the study itself. I did not feel the need to quote that part of Mike's article, because that's not the point of the article.


So when Mike Hall finally, after a misleading headline and introduction, gets to the actual point of the article, "that's not the point of the article," in your opinion.
That's a very convoluted argument! It's also interesting that it took Mike Hall so long after you allegedly sent it to him:
I'm also willing to bet that Mike Hall is going to talk about this on the show, because I'm going to send it to him after I have watched it.


I wonder why it took him so long ...

No, as Roger points out below, this is pretty much what the paper concludes. Classical conditioning can produce an endorphin response in the absence of actual pain. The fallacy that is being reported is that this is the entire definition of the placebo effect. It isn't.


It only isn't because you (and Mike Hall) insist on defining the placebo effect as everything that may give the impression that pain is being relieved in the brain-body of an individual, including confounding factors, which is nonsense.

The paper concludes that they have documented a mechanism for an effect that has previously been assumed to be placebo. But by documenting it, it is no longer placebo. There is an actual mechanism involved beyond "mind over matter" which is what the public at large believes the placebo effect is, thanks to people like Ted Kapchuk and others who promote this belief.


So by documenting a pain-relieving effect in the brain-body of the individual mouse that cannot possibly be dismissed as a confounding factor, they have documented something that isn't placebo?!
That is nonsense!
You confuse it with the argument that when documenting an actual beneficial effect of traditional medicine, it stops being alt.med. and becomes an integral part of science-based medicine instead.
It's not at all the same thing!

In order to avoid playing around with definitions and words:
The study appears to have discovered a pain-relieving effect in mice based on their previous experiences with a behavior that relieved pain, i.e. moving to a place that didn't induce pain. And it turns out that the mice seem to continue to feel a relief from pain when moving to the same place even when that place objectively exposes them to the same level of heat.

I would call that the real placebo effect, i.e. what is left when the confounding factors have been removed. You, on the other hand, would like to call it something else, and you are obviously free to do so.
 
I'm with Arth on this one. The analogy would be, a paper comes out where they can successfully prevent basal cell carcinoma from progressing, and the reporting says 'scientists finally find the trick to preventing skin cancer!'

That Arth was overly skeptical of the paper before looking at it is orthagonal to his point about pop science reporting.

His other bit about 'if there's a demonstrable mechanism/effect it's not placebo' is a linguistic argument like '(...) then it's not alternative medicine, it's just medicine' and I have no dog in that race.
 
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I'm with Arth on this one. The analogy would be, a paper comes out where they can successfully prevent basal cell carcinoma from progressing, and the reporting says 'scientists finally find the trick to preventing skin cancer!'
Sure, I think we all agree about that point.

That Arth was overly skeptical of the paper before looking at it is orthagonal to his point about pop science reporting.
Yes, also agreed.

His other bit about 'if there's a demonstrable mechanism/effect it's not placebo' is a linguistic argument like '(...) then it's not alternative medicine, it's just medicine' and I have no dog in that race.

That seems to be pretty important to the subject of this thread, though, don't you think? Is there some effect where the expectation that a treatment can cause physiological changes similar to what was expected of that treatment? Or is there no such effect but there are only confounding factors, such as regression to the mean, social expectations, etc? The claim at the start of this thread is the latter: that there is no actual physiological effect.
The linguistic claim that Arth is making is that to the extent that such an effect exists, it's not the placebo effect.

This is just defining the placebo effect out of existence. The real scientific question is whether or not such an effect exists. To dismiss evidence that such an effect exists on the basis that having discovered it, it's no longer placebo, seems ridiculous to me.

When doing placebo controlled trials, the reason to control for placebo is to control for all of these things. That includes any real effect and all possible confounding factors. In that case we don't really care whether what we're controlling for is real (because insomuch as the placebo controls for it, it exists for the actual treatment as well as the sham treatment), we just care about detecting the signal of the actual treatment.

But if you want to ask the question "is there a real physiological mechanism underlying the placebo effect?" then you have to accept the possibility that the answer is yes. If you define the term such that any such mechanism can't be placebo, then what are you even asking?
 
I wonder why it took him so long ...
Well, because he has a job, and a family, and always talks about things on the podcast before cleaning them up for the magazine, and that's on a two-weekly schedule.

In order to avoid playing around with definitions and words:
The study appears to have discovered a pain-relieving effect in mice based on their previous experiences with a behavior that relieved pain, i.e. moving to a place that didn't induce pain. And it turns out that the mice seem to continue to feel a relief from pain when moving to the same place even when that place objectively exposes them to the same level of heat.
And if they'd reported it as such without referring to the placebo effect at all, there would have been no problem. But no, this is THE placebo effect according to the reporting.

But if you want to ask the question "is there a real physiological mechanism underlying the placebo effect?" then you have to accept the possibility that the answer is yes. If you define the term such that any such mechanism can't be placebo, then what are you even asking?
The point is there is no one placebo effect. The placebo effect is a blanket term covering a range of uncontrolled variables. The referenced article controls and isolates one variable. That doesn't mean that "the placebo effect" is explained.
 
The point is there is no one placebo effect. The placebo effect is a blanket term covering a range of uncontrolled variables. The referenced article controls and isolates one variable. That doesn't mean that "the placebo effect" is explained.

I certainly don't think that everything that falls under the blanket term "placebo effect" is an actual physiological mechanism. I do think that there's a real question as to whether or not such mechanisms exist. And if they do, they are part of the placebo effect.

I've already said I agree with you about the issue of hyperbolic articles saying that the placebo effect has been explained. It's clear that in many cases there probably isn't any such physiological mechanism.

That doesn't mean that in cases when such a mechanism exists, such as in the mouse study, it's not a placebo effect.

Aren't you interested in the question of whether or not such mechanisms exist?
 
I certainly don't think that everything that falls under the blanket term "placebo effect" is an actual physiological mechanism. I do think that there's a real question as to whether or not such mechanisms exist. And if they do, they are part of the placebo effect.

I've already said I agree with you about the issue of hyperbolic articles saying that the placebo effect has been explained. It's clear that in many cases there probably isn't any such physiological mechanism.

That doesn't mean that in cases when such a mechanism exists, such as in the mouse study, it's not a placebo effect.

Aren't you interested in the question of whether or not such mechanisms exist?
I'm a bit confused as to why when something is known and controlled, it somehow is still part of a placebo effect. The placebo effect is defined as all of the responses that are not controlled for.

Yes. They have documented a method by which classical conditioning can cause the release of endorphins in the absence of a pain stimulus. That means that this particular mechanism is no longer part of the placebo effect, by definition.

It also, more importantly, goes towards dispelling the idea that such effects are magical, somehow "mind over matter" effects, as Kapchuk and others claim.
 
I'm a bit confused as to why when something is known and controlled, it somehow is still part of a placebo effect. The placebo effect is defined as all of the responses that are not controlled for.

Yes. They have documented a method by which classical conditioning can cause the release of endorphins in the absence of a pain stimulus. That means that this particular mechanism is no longer part of the placebo effect, by definition.

So when you say that the placebo effect is a sham, you are explicitly not saying that the idea that the expectation that, for instance, a pain medication will relieve pain, will itself cause pain relief (perhaps by the release of endorphins), even if the patient is given a sugar pill, is a sham?

You're saying, such effects, if they exist, just aren't the placebo effect.

Let's say we find, through clever controlled experiments, that a mechanism exists in humans similar to the mechanism that we discovered in mice. The next time someone studies a pain medication, based on these experiments, they expect that mechanism to come into play. However, they don't have the time or expertise to tease out this effect from other potential confounders. Instead, they just give half of their experimental subjects a sugar pill. Part of the thing they are controlling for with this placebo will be the actual effect of the release of endorphins associated with the expectation of pain relief in the placebo group. If they didn't give placebo, and just had a separate control group that didn't get any treatment, this effect would exist in those given the medication but not the control group and would confound their results, leading them to report a higher efficacy of their medication than is actually justified. It seems to me that if this effect exists, we should be controlling for it when studying new medicines, and placebo controlled studies do control for it. So to not call it placebo is completely unjustified.

The fact that we can potentially track down the different aspects of placebo doesn't make them not placebo.
 
So when you say that the placebo effect is a sham, you are explicitly not saying that the idea that the expectation that, for instance, a pain medication will relieve pain, will itself cause pain relief (perhaps by the release of endorphins), even if the patient is given a sugar pill, is a sham?

You're saying, such effects, if they exist, just aren't the placebo effect.
I'm saying that such effects, if they exist, are an effect.

I don't quite know why but I'm having trouble parsing your next paragraph, so let's cut to the chase.

The fact that we can potentially track down the different aspects of placebo doesn't make them not placebo.
Why would they be? If they are known and can be controlled for, why are they still placebo? That doesn't make sense.
 
Why would they be? If they are known and can be controlled for, why are they still placebo? That doesn't make sense.

Because when we use placebo controls, they are one of the things that's being controlled for.

We also know that the effect "people experience social pressure to say the medicine makes them feel better" is a real effect that can be controlled for (we control for it using placebos), that doesn't mean it's not part of the placebo effect.

Every aspect of the placebo effect can at least potentially be known and controlled for. Why would that make them not placebo?
 
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