That reminds me of the idea that brain as a predictive engine that constantly refine its internal model to match anticipated sensory outcome. In this case the inference is way more complex based on cognition that the placebo would help relieve pain.
Based on this idea, however, the study does not identify the key pathway responsible for placebo effect, but only the result of it. If the brain anticipate relief of pain, the parts related to pain would activate. If it anticipates other effects, other parts of the brain would do.
My likely oversimplified understanding of dopamine is that the brain is constantly simulating the outcomes of possible actions. Simulated actions that result in "success" states generate dopamine, with different pathways generating varying levels at any one time. The pathway that generates the greatest net dopamine is pursued, the realized outcome of which then reinforces/dampens the path's simulation function by generating other neurotransmitters.
Could perhaps be about reducing the cost structure of forming connections in the pathway while increasing in some, and thus more likely that some connections are formed/deformed (ie without the actual presence of agonists/antagonists)?
> brain as a predictive engine that constantly refine its internal model
And a pretty effective one at that. Stereotype accuracy is one of the most solid and replicable findings in psychology. There are very strong correlations between what people think is true about statistical discrepancies between groups and what the truth actually is. The relationships consistently replicate and are much stronger than most effects found in social psychology [0].
We must thus understand wokeism as a war on pattern recognition.
> 7. The Placebo Effect. We hear a lot about “pain gating” in the spine, but the PP model does a good job of explaining what this is: adjusting pain based on top-down priors. If you believe you should be in pain, the brain will use that as a filter to interpret ambiguous low-precision pain signals. If you believe you shouldn’t, the brain will be more likely to assume ambiguous low-precision pain signals are a mistake. So if you take a pill that doctors assure you will cure your pain, then your lower layers are more likely to interpret pain signals as noise, “cook the books” and prevent them from reaching your consciousness.
> Psychosomatic pain is the opposite of this; see Section 7.10 of the book for a fuller explanation.
While I always thought placebo (and nocebo) is quite amazing, I've had that tempered from some reading of it perhaps not being a large effect beyond a regression to the mean. For example, here's one paper [0], with a quote from the abstract "Analysis of the trial outcomes demonstrated that the reduction observed in the placebo group was of the same magnitude as predicted by regression to the mean."
Or from [1] in their summary: "In clinical practice, the phenomenon [regression to the mean] can lead to misinterpretation of results of tests, new treatments, and the placebo effect"
This has been discussed in some popular sources as well, like the fun book The Math of Life and Death by Kit Yates.
Edit: see also this helpful explanation elsewhere in the comments [2]. The thread there highlights this paper [3] with the key conclusion of "There was no evidence that placebo interventions in general have clinically important effects. A possible moderate effect on subjective continuous outcomes, especially pain, could not be clearly distinguished from bias."
It's likely that the placebo/nocebo effect is confounded by regression to the mean - a typical example are diseases with some sort of cyclical pattern, e.g. some forms of depression.
But there is strong evidence that there is an effect beyond that: E.g. cancer patients die significantly sooner when they get a negative prognosis [1]. Acupuncture is so effective for treating certain forms of chronic (!) pain that in some cases it's covered by German health insurance since 2007 [2]. If you have been treated in a hospital for pain related issues, e.g. after a surgery, it's not unlikely you have received placebo instead of pain killers (depends a lot on jurisdiction).
Regarding [3] specifically, the obvious elephant in the room is that 'absence of evidence is not evidence of absence'. Also see the refutations pointed out by user PaulDavisThe1st [4]. What I take away from that study is that yes, in some contexts, regression to the mean may account for a major portion of the placebo effect.
It's been experimentally shown that the placebo effect is enhanced by being administered in a hospital-like setting, by a person dressed as a doctor, with a big + on a big pill.
My personal theory is that if you have convincing evidence that you are safe and being looked after, your body can divert resources to deal with the problem, instead of being on guard.
I agree. Similarly relativism can evaporate some pain. You can feel pretty bad if you think you're alone in a situation. Just knowing someone went through the same issue relieves part of the pain, even though nothing changed in your life.
Which begs the question: If placebos (sometimes) work, (particularly when administered in hospital settings and when expensive, at least in the eyes/brain of the patient) is it unethical to administer/provide them?
I've never understood placebos. Naively you'd assume they work the other way around, as the body attempts to achive homeostatis. So if you think you have taken a pain killer, the body would ramp up pain sensitivity to counter it. But as far as I know a lot of studies have shown placebos work.
One thing I haven't seen discussed is that maybe there is a subconcious social pressure element to placebos. Like: I just got a big injection from the doctor, surely it is going to help, I can't complain yet again about it. Sometimes I wonder, what if people take a placebo, report that they feel better, but continue to suffer internally? And are not even able to identify this, because their internal pain gauge is affected by the placebo. They think it helps. Maybe you could detect this by non-voluntary indicators of pain - avoidance reflexes, concentration loss, etc..
Back to the homeostatis argument, there are placebo-like effects that accidentially work. In autogenic training, you can warm up your body parts by imagining fire. What I think happens is, the body anticipates heat, widens the blood vessels to regulate against the heat, but in the cold environment this actually warms up your arms or legs.
For social species, when resources are limited, evolution favors groups whose rejected members fall sick and die.
The placebo effect comes from social support and goes beyond pain.
As for the implementation details, expectations play a role. A drug that modulates the cholecystokinin neurotransmission in the brain (involved in expectation processing) was found to enhance the placebo effect of a placebo pill (on mobile, can’t search right now, but with “ cholecystokinin” and “placebo” you should find the paper on google scholar).
I think my favourite simple example to illustrate this is thinking of (or image searching a picture of) a lemon. A lot of people can feel increased saliva production under their tongue, despite nothing at all actually changing, in anticipation of the sourness. Brains are magical :)
You are onto something factoring social pressure. Social pressure has a direction, if a doctor says you are going to get better it is creating a pressure on yourself to get better. In many cases that pressure might be all you need.
The homeostasis effect might happen in an adversial situation. Say instead of a doctor, an opponent says something. It might cause to overcompensate in the opposite way. We could call that reverse placebo or by its more common name "spite".
I'd never thought about placebo's being a social mechanism.
As a bit of a tangent, one of things I've always wondered is "how much pain do animals feel compared to humans?" The null hypothesis here would be that they feel the same amount, of course. On the other hand, what's an animal going to do with joint pain? Humans are unique in our ability to perform interventions. Suppose two people have cancer, one shows symptoms and one does not. A tumor can be excised before it becomes malignant. One would live and the other would die. Is there a pressure on us to have pain so that we can seek treatment?
To bring this around to your comment. I wonder if we've demonstrated placebo effects on animals. That seems like an awfully hard study to conduct.
There is a lot to how you perceive something that influences how you will react to what's going on.
I was just today thinking about the difference between how both my children were born. There were so similar in the time they happened, how they were late, how the birth was triggered etc. But in the first case we were picked up by an emergency vehicle (there was no emergency, they just told us to do this), so it was dark, with this scary blue light as if somebody is dying, to some hectic in the hospital. And in the second we went very quietly to our appointment, rode the bus on a sunny day, took a relaxing walk outside the hospital as we were waiting etc.
When it was done with the first, my wife was pale and shivering, completely out of everything, and with the second she was just exhausted but could still smile and enjoy taking our newborn. And she looked happy.
Of course there is the case of the first being more scary because of the unknowns, but you could also make a case that it was so traumatic that it should've ruined the second one.
I also fell down on ice once and had a case of whiplash. I got worried as I was reading about the potential long term, especially in the US. And I then switched to the German Wikipedia that said doctors in Germany tell patients to relax for a few days and it will go away, and that long term issues are virtually unknown.
You could go on and on really. When you go to a doctor and they have almost no time for you, you will not feel better. Compare that with going in to somebody doing homeopathy. A friend told me they went and got a cup of tea and an hour to talk about their health issues.
Is there any research into the variation of susceptibility to placebos? My gut feeling is that there are people who are much more susceptible and those who are much less, and I’m curious if that’s supported by any research and, if so, how that difference is developed.
Also, I’m confused by the conclusion of the article. If they’re literally exciting or dampening a control pathway in the brain that controls pain, how is this placebo/nocebo? Sounds like a straight up causal effect, not a vague one controlled by the patient’s expectation….
This is the connection more people should be making. The placebo effect is a social effect. Somebody else whom you trust has given you something. More generally it is an expectation, but the double-blind nature of placebo studies means that it is also always a social transaction. The effect is boosted by the perceived authority of the prescriber (white coat, hospital, colored pill). The same mechanism probably underlies higher survival of religious-minded cancer patients.
This article/study is all and only about "pain modulation".
Is it to say that there is only one placebo effect, which is always reducing pain?
Aren't there placebo effects going "beyond" pain relieving?
(Or is it the title that is generalizing the scope of the analysis too much?)
Psychological effect can amplify the pain you are experiencing. By really noticing and associating the pain with something worse than it is, it makes it hurt more. Placebo can take your mind off it and make it less noticeable.
The reason it works is because consciousness is fundamental to reality as shown by double slit experiments. The viewer creates their reality. A tree doesn’t fall in the woods if no one is there to see it.
I would love to see a thread of people describing their own placebo responses, but one difficult part of understanding the response is that few people will admit to it.
Seems strange they would use petroleum jelly which is a well known treatment for burns. It is not a placebo; it's not inert like sugar pill or saline. This could seriously skew the results towards "pain relief" end of spectrum.
It’s a moisturizer that treats water loss and protects skin in the presence of real burns. It doesn't do anything to pain. These people weren’t burned. And I think Lubaderm is more commonly “well known” these days.
Yes, that's the reason RCTs are contrasted against placebo not no treatment.
If you want too see how powerful this effect can become look no further than acupuncture. Or, for a nocebo result, people have actually died because they thought they had been cursed. Or, maybe less dramatic, people who are given an alcohol placebo still get drunk.
Not all, but some do, and we don't know why they specifically and why at all.
[+] [-] andrewon|4 years ago|reply
Based on this idea, however, the study does not identify the key pathway responsible for placebo effect, but only the result of it. If the brain anticipate relief of pain, the parts related to pain would activate. If it anticipates other effects, other parts of the brain would do.
[+] [-] nefitty|4 years ago|reply
[+] [-] archibaldJ|4 years ago|reply
[+] [-] MrBuddyCasino|4 years ago|reply
And a pretty effective one at that. Stereotype accuracy is one of the most solid and replicable findings in psychology. There are very strong correlations between what people think is true about statistical discrepancies between groups and what the truth actually is. The relationships consistently replicate and are much stronger than most effects found in social psychology [0].
We must thus understand wokeism as a war on pattern recognition.
[0] https://cspicenter.org/reports/the-accuracy-of-stereotypes-d...
[+] [-] rtkaratekid|4 years ago|reply
[+] [-] gfody|4 years ago|reply
> 7. The Placebo Effect. We hear a lot about “pain gating” in the spine, but the PP model does a good job of explaining what this is: adjusting pain based on top-down priors. If you believe you should be in pain, the brain will use that as a filter to interpret ambiguous low-precision pain signals. If you believe you shouldn’t, the brain will be more likely to assume ambiguous low-precision pain signals are a mistake. So if you take a pill that doctors assure you will cure your pain, then your lower layers are more likely to interpret pain signals as noise, “cook the books” and prevent them from reaching your consciousness.
> Psychosomatic pain is the opposite of this; see Section 7.10 of the book for a fuller explanation.
[+] [-] grp000|4 years ago|reply
[+] [-] WORMS_EAT_WORMS|4 years ago|reply
[+] [-] podiki|4 years ago|reply
Or from [1] in their summary: "In clinical practice, the phenomenon [regression to the mean] can lead to misinterpretation of results of tests, new treatments, and the placebo effect"
This has been discussed in some popular sources as well, like the fun book The Math of Life and Death by Kit Yates.
[0] https://pubmed.ncbi.nlm.nih.gov/15975061/
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1125994/
Edit: see also this helpful explanation elsewhere in the comments [2]. The thread there highlights this paper [3] with the key conclusion of "There was no evidence that placebo interventions in general have clinically important effects. A possible moderate effect on subjective continuous outcomes, especially pain, could not be clearly distinguished from bias."
[2] https://news.ycombinator.com/item?id=29025886
[3] https://pubmed.ncbi.nlm.nih.gov/12535498/
[+] [-] Pyramus|4 years ago|reply
It's likely that the placebo/nocebo effect is confounded by regression to the mean - a typical example are diseases with some sort of cyclical pattern, e.g. some forms of depression.
But there is strong evidence that there is an effect beyond that: E.g. cancer patients die significantly sooner when they get a negative prognosis [1]. Acupuncture is so effective for treating certain forms of chronic (!) pain that in some cases it's covered by German health insurance since 2007 [2]. If you have been treated in a hospital for pain related issues, e.g. after a surgery, it's not unlikely you have received placebo instead of pain killers (depends a lot on jurisdiction).
Regarding [3] specifically, the obvious elephant in the room is that 'absence of evidence is not evidence of absence'. Also see the refutations pointed out by user PaulDavisThe1st [4]. What I take away from that study is that yes, in some contexts, regression to the mean may account for a major portion of the placebo effect.
[1] https://doi.org/10.1016/S0140-6736(73)91754-6
[2] https://www.verbraucherzentrale.de/wissen/gesundheit-pflege/...
[3] https://pubmed.ncbi.nlm.nih.gov/12535498/
[4] https://news.ycombinator.com/item?id=29028133
[+] [-] hyperpallium2|4 years ago|reply
My personal theory is that if you have convincing evidence that you are safe and being looked after, your body can divert resources to deal with the problem, instead of being on guard.
[+] [-] agumonkey|4 years ago|reply
[+] [-] jrs235|4 years ago|reply
[+] [-] captainmuon|4 years ago|reply
One thing I haven't seen discussed is that maybe there is a subconcious social pressure element to placebos. Like: I just got a big injection from the doctor, surely it is going to help, I can't complain yet again about it. Sometimes I wonder, what if people take a placebo, report that they feel better, but continue to suffer internally? And are not even able to identify this, because their internal pain gauge is affected by the placebo. They think it helps. Maybe you could detect this by non-voluntary indicators of pain - avoidance reflexes, concentration loss, etc..
Back to the homeostatis argument, there are placebo-like effects that accidentially work. In autogenic training, you can warm up your body parts by imagining fire. What I think happens is, the body anticipates heat, widens the blood vessels to regulate against the heat, but in the cold environment this actually warms up your arms or legs.
[+] [-] pygy_|4 years ago|reply
The placebo effect comes from social support and goes beyond pain.
As for the implementation details, expectations play a role. A drug that modulates the cholecystokinin neurotransmission in the brain (involved in expectation processing) was found to enhance the placebo effect of a placebo pill (on mobile, can’t search right now, but with “ cholecystokinin” and “placebo” you should find the paper on google scholar).
[+] [-] notjosh|4 years ago|reply
[+] [-] iamcurious|4 years ago|reply
The homeostasis effect might happen in an adversial situation. Say instead of a doctor, an opponent says something. It might cause to overcompensate in the opposite way. We could call that reverse placebo or by its more common name "spite".
[+] [-] oehpr|4 years ago|reply
As a bit of a tangent, one of things I've always wondered is "how much pain do animals feel compared to humans?" The null hypothesis here would be that they feel the same amount, of course. On the other hand, what's an animal going to do with joint pain? Humans are unique in our ability to perform interventions. Suppose two people have cancer, one shows symptoms and one does not. A tumor can be excised before it becomes malignant. One would live and the other would die. Is there a pressure on us to have pain so that we can seek treatment?
To bring this around to your comment. I wonder if we've demonstrated placebo effects on animals. That seems like an awfully hard study to conduct.
[+] [-] locallost|4 years ago|reply
I was just today thinking about the difference between how both my children were born. There were so similar in the time they happened, how they were late, how the birth was triggered etc. But in the first case we were picked up by an emergency vehicle (there was no emergency, they just told us to do this), so it was dark, with this scary blue light as if somebody is dying, to some hectic in the hospital. And in the second we went very quietly to our appointment, rode the bus on a sunny day, took a relaxing walk outside the hospital as we were waiting etc.
When it was done with the first, my wife was pale and shivering, completely out of everything, and with the second she was just exhausted but could still smile and enjoy taking our newborn. And she looked happy.
Of course there is the case of the first being more scary because of the unknowns, but you could also make a case that it was so traumatic that it should've ruined the second one.
I also fell down on ice once and had a case of whiplash. I got worried as I was reading about the potential long term, especially in the US. And I then switched to the German Wikipedia that said doctors in Germany tell patients to relax for a few days and it will go away, and that long term issues are virtually unknown.
You could go on and on really. When you go to a doctor and they have almost no time for you, you will not feel better. Compare that with going in to somebody doing homeopathy. A friend told me they went and got a cup of tea and an hour to talk about their health issues.
So the body is obviously complicated.
[+] [-] vlovich123|4 years ago|reply
Also, I’m confused by the conclusion of the article. If they’re literally exciting or dampening a control pathway in the brain that controls pain, how is this placebo/nocebo? Sounds like a straight up causal effect, not a vague one controlled by the patient’s expectation….
[+] [-] cariaso|4 years ago|reply
https://www.snpedia.com/index.php/Rs4680
and the others mentioned at
https://www.snpedia.com/index.php/Placebo
[+] [-] lngnmn2|4 years ago|reply
Religious and mystic experiences work exactly the same way. When many other people around you do strange things they start to make sense.
So, basically, it is fooling of neural nets by giving strong cues or whatever you might call them.
In religion such strong cues are other people's facial expressions and body language.
The brain's neural networks recognize strong signals of "taking positive actions" or whatever.
[+] [-] ramblenode|4 years ago|reply
[+] [-] mathattack|4 years ago|reply
[+] [-] wolverine876|4 years ago|reply
[+] [-] unknown|4 years ago|reply
[deleted]
[+] [-] Noe2097|4 years ago|reply
Is it to say that there is only one placebo effect, which is always reducing pain? Aren't there placebo effects going "beyond" pain relieving? (Or is it the title that is generalizing the scope of the analysis too much?)
[+] [-] m3kw9|4 years ago|reply
[+] [-] paperoli|4 years ago|reply
[+] [-] richardatlarge|4 years ago|reply
https://static.substack.com/p/now-available
[+] [-] twofornone|4 years ago|reply
I guess ignorance really is bliss.
[+] [-] unknown|4 years ago|reply
[deleted]
[+] [-] wolverine876|4 years ago|reply
[+] [-] dr-detroit|4 years ago|reply
[deleted]
[+] [-] tantalor|4 years ago|reply
[+] [-] dcow|4 years ago|reply
[+] [-] dairylee|4 years ago|reply
Can it? I don't believe there are any studies that actually show this.
[+] [-] Pyramus|4 years ago|reply
If you want too see how powerful this effect can become look no further than acupuncture. Or, for a nocebo result, people have actually died because they thought they had been cursed. Or, maybe less dramatic, people who are given an alcohol placebo still get drunk.
Not all, but some do, and we don't know why they specifically and why at all.
[+] [-] wyager|4 years ago|reply