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.
an example of the complexity of dopamine: a study allowed animals to self-administer cocaine. Other animals were administered the drug in the brain on the same schedule but without 'choosing' to take it. The findings showed that the areas of the brain affected differed depending on these two conditions. This is a study with rats, and yet the effects of a seemingly small environmental/psychological difference changed everything
Another study on electrical brain stimulation showed that while animals would self-administer it, when it was automatically administered, the same animals would respond always to turn it off
Wow, that is weird! What's your favorite book or resource to learn more about the brain? I've looked at the deep end of neuroscience Wiki and it is super overwhelming.
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.
Prejudice is a serious problem - the most serious one. The horrors it has inflicted on people are a long catalog, maybe the worst one. What do you hope to achieve by supporting it?
The underlying issue is about reactionary politics, which exists only to stop progress. I think if we look deep down, we know reactionary politics will object no matter what the issue or facts - therefore the objection has nothing to do with the question at hand or its outcomes. You can see it in climate change denial, as a simpler example. That is its purpose and reason - to object. Along the way, lots and lots of people will die and suffer. Blood, lost generations, are on our hands. And for what?
These are baseless assertions, absurd on their face, supporting hate. Why is that important to you? If you think you are fighting a political war, avoid the mistake that many before you have made - becoming so caught up in the mob dynamics, the cause, the obsession - that you disregard the consequences. Don't say later, 'I didn't think' - that's fine for a night out, but it's not good enough when people's lives and welfare is at stake.
Everyone faces prejudices from some others; should everyone act on them? What kind of society will we have? On a practical level, how does that bring freedom and economic opportunity.
You have a great model that has been far more successful than anything in the history of humanity, the free world, based on universal human rights and equality. The (general) lack of prejudice where I live works wonderfully; the bigotry - almost always from outsiders who have no experience with the people they hate - is the only problem. If they all went away, we'd have one less problem.
That is a bold, unfounded, unappreciated accusation. I do not support hate. I support gut feelings borne in truth. I will continue to not give free car rides to homeless people and to offer to help carry groceries out to the cars of little old ladies in front of me in line at the grocery store - because yes, stereotypically, the homeless are more likely to be drug addicts, mentally unstable, and have a criminal record, and little old ladies are more likely to need assistance carrying things. I don’t hate homeless people nor do I hate little old ladies or consider them inferior. But please, feel free hire someone with face tattoos to be your child’s bus driver in the interest of ignoring all prejudice at all costs. The rest of us will continue to make decisions using common sense, regardless of what Twitter has to say about the matter.
> The (general) lack of prejudice where I live works wonderfully; the bigotry - almost always from outsiders who have no experience with the people they hate - is the only problem. If they all went away, we'd have one less problem.
Could it be you’re wrongly conflating prejudice with hate? Don’t discount peoples’ life experiences either. Furthermore, your example is anecdotal. There’s a plethora of widespread non-anecdotal data to back up “prejudice” being accurate and helping people make wiser decisions.
We all know very well where it leads, and knowing that, it's hard to escape that it's the intent of such comments. Protests to the contrary and disingenuous arguments are well-worn, unconvincing, and part of the usual routine.
> The (general) lack of prejudice where I live works wonderfully; the bigotry - almost always from outsiders who have no experience with the people they hate - is the only problem. If they all went away, we'd have one less problem.
Beautiful. This one goes into the collection of all time memorable HN comments.
I don't see that as "supporting" it, with the exception of maybe the one line about wokeism. However, I do think it would serve well to better understand the mechanisms behind stereotyping.
> Prejudice is a serious problem - the most serious one.
I take it you have studied all the serious problems, so that you could come to the conclusion that this is indeed the most pressing one. Investing many years into studying human nature, the rise and decline of ancient civilisations plus the majority of philosophy is admirable! You don't happen to have written down any notes?
Think further downstream, beyond the pain sensing part of the brain.
So opioids are know to be great pain relievers. What is interesting is for certain types of pain, they don’t actually make the pain go away, they just change the perception and emotional response to it.
Patients who receive opioids say “i can still feel the pain, but it doesn’t bother me now”.
So to your question, the impact of opioids isn’t necessarily on the pain sensing centers but rather further downstream in terms of how those sensations are perceived.
If you take a placebo and expect it to relieve pain, your brain adjusts to assume that outcome.
It’s not that different than asking you if you’re tired right now. If you have to go to work you might say “yes”, but if you’re about to jump on a plane for a vacation you might say “no”.
> 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.
Good points, and I didn't mean to say that there isn't some placebo/nocebo effect. There's lots of evidence for the connection between mind and body, so it certainly seems plausible this happens (also not a medical expert).
I've always found the placebo effect fascinating, but does seem, at least in popular coverage?, to be puffed up more when there's a lot we don't know. And of course it can be very hard to untangle when some people will just get or feel better for who knows what reason. Medical and human research can be very messy, much as the physicist in me just wants to see the hard stats showing a strong (causal) relationship.
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?
Placebos work even when people know it's a placebo. We might want to establish a baseline, like the pretender has to remind the patient he's just a pretender once a year. But if a pretend doctor can help, then go for it.
I 100% agree, but that doesn't mean we can't still administer placebos:
I've read elsewhere that you don't have to lie to the person to still have a successful placebo effect- they can still receive a benefit even knowing it's not a real drug.
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).
> evolution favors groups whose rejected members fall sick and die.
Do you have a source on this? I don't understand how evolution could favor such a negative trait on the individual level, and as far as I understand group selection has been mostly rejected by modern evolutionary biologists
It's true that some reject the idea of group selection, but there are lots of scientists too who embrace the idea. Lots of very good talks/interviews on YouTube with scientists & researchers on the subject.
IMO there are too many phenomena that are very difficult to explain only with individual selection, but trivial to explain with group selection.
Not sure about the claim that evolution favors groups whose rejected members die (not sure what rejected even means in this context), seems to me like that would depend a lot on environmental context and vary across species and across time.
It seems to me that you have cause and effect backwards. I think the most likely chain of events is something like this:
Member gets sick
Member gets rejected from the group (because for each individual in the group, it's better to avoid the sick member - no group selection necessary)
Member dies
So the member doesn't get sick because they're rejected - they get rejected because they are sick. This would have obvious benefits for each individual that rejects the sick member, regardless of the behavior of the rest of the group (https://esajournals.onlinelibrary.wiley.com/doi/abs/10.2307/...)
Could you explain that link between health and status a bit more?
I vaguely remember reading adverse health outcomes in lower status individuals may be linked to the chronic stress attributed to being low status, but can't remember the exact source but this one came up in a quick search:
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.
Based on limited conversation with researchers, they are constrained by budget for experimental subjects and other resources (equipment, drugs, staff, etc.).
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.
That’s fine, I’ll easily believe “medical research can make no accurate predictions in this domain” - in fact, that’s my prior. In any case, people shouldn’t go around speaking as if placebo is this established strong phenomenon.
Exactly. Thanks, I had forgotten where I had read that, this is a nice source.
Here's the TL'DR: The placebo effect is maybe not quite as powerful as it is sometimes made out to be. And the reason is spontaneous remission or reversion to the mean.
1. Initially, researchers tested a treatment, and when the patients got healthier, it was assumed that it was the treatment.
2. Then researchers got smarter, and tested a treatment against a placebo (control), ideally double blind and randomised etc., and when the control group got better, it was assumed to be the placebo effect, and when the treatment group got even better, the difference was the treatment effect.
3. Then researchers got even smarter, and tested a treatment against a placebo (control) and against no treatment at all, and when the no-treatment group got better, it was assumed to be reversion to the mean or spontaneous remission; when the control group got even better, that difference was the placebo effect; and when the treatment group got even better, that difference was the treatment effect.
Going from 1. to 2., it was realised that many treatments are not quite as potent as hoped, and that the placebo effect is quite strong. However, going from 2. to 3., it was realised that the placebo effect is not quite as potent either, and that there is considerable spontaneous remission or reversion to the mean.
You are not wrong - placebos are a practical way to blind a study.
The best way to blind, however, is no treatment, but no treatment only gives you the efficacy of the treatment, and not what you actually want to know, the efficacy of the 'active ingredient'.
I don't know of people dying from a belief that they were cursed, but we do certainly know that placebos can have very real, measurable neurobiological effects. For example, there many studies looking at the body's response to placebo painkillers. The brain often releases neurotransmitters that bind to opioid receptors as if an actual painkiller had been taken: https://www.nature.com/articles/535S14a
The original comment was about placebos bringing "powerful relief," which there is a great deal of scientific research to support. As far as I'm aware, there is no serious medical researcher advancing the hypothesis that stage 4 cancer or type 1 diabetes should or can be treated via placebos.
Generally in medicine there's a distinction between acute conditions and chronic conditions.
Allopathic (western) medicine has proved highly effective at treating acute conditions, including trauma/injury, certain forms of cancer and infection.
However, chronic conditions are still one of the primary experiences of many humans relating to their health, and allopathic medicine has generally done quite poorly at addressing these conditions. Other styles of treatment, including placebo, have been shown to be effective in at least reducing the severity or incidence of the symptoms associated with chronic conditions.
The fact that you don't want to consider someone's 20 year battle with chronic back pain, or neuropathy, or any other chronic condition, to be "an objective malady" doesn't make you the arbiter of what's real and what isn't.
> The fact that you don't want to consider someone's 20 year battle with chronic back pain, or neuropathy, or any other chronic condition, to be "an objective malady" doesn't make you the arbiter of what's real and what isn't.
Objective means measurable, definable, quantifiable. It has nothing to do with real or not. The human body is so complex with so many possibilities, I find it uninteresting to speculate about unknowns, hence restricting my request to what I am interested in.
Dying is an objective condition observable by others, so it piqued my interest as to how it was determined someone died due to a nocebo.
Most/many chronic conditions cannot be measured, defined, or quantified. The sufferer can give you some estimate on some scale that you describe that relates to the intensity and nature of their experiences.
I'm very glad to have seen an increasing number of health care professionals say things along the lines of "we have no idea what is causing their experience, and in fact, we think most it may be entirely psychogenic, but that doesn't change the fact that this is what they are actually experiencing, and that's as real for them as a puncture wound or an infection."
I'm not up to date on if there are any counter opinions to this, but I've heard that placebo's are similar in effect to SSRIs[1] - Though as always there's a lot of buts/ifs there.[2] My assumption is that a placebo causes people to expect things to get better and reduces stress levels, increases sleep quality and so on. I would figure a very supportive social network (family, prayer group) would probably have a similar effect.
That being said like you say for something more severe the placebo alone isn't going to do much, but I would imagine if you gave people a placebo that they thought would improve their stage 4 cancer recovery you would probably see an effect.
Do you expect a single study to overturn decades of research and medical practice? Leaving aside that 'absence of evidence is not evidence of absence', that would need to be extraordinary evidence, right?
I'm not surprised at all you doubt the existence - it's a very common phenomenon that modern medicine/science struggles to explain (yet) and it's a very weird phenomenon. E.g. placebos still work when you know it's a placebo, it works for animals, it works so well that insurance will cover it etc.
Maybe Bad Science by Ben Goldacre is a good starting point as a book.
> to overturn decades of research and medical practice?
“Medical practice” has an atrocious record of being based in fact. There is, in fact, plenty of research on placebo, and the preponderance seems to suggest that it’s weak or non-existent.
> E.g. placebos still work when you know it's a placebo, it works for animals
This is consistent with, and in fact favors, the theory that it’s actually just mean reversion.
> Maybe Bad Science by Ben Goldacre is a good starting point as a book
I don’t think pop scientism books are a good place to start.
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.