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What if the Placebo Effect Isn’t a Trick? (nytimes.com)
347 points by sajid 10 days ago | hide | past | web | favorite | 278 comments





I listened to an episode about the placebo effect on the "Only Human" Podcast awhile back. Its truly fascinating, and has made me question the power of the mind in a way I hadn't before. It also has some really interesting ethical problems, is it okay for doctors to lie about placebo treatments if it actually helps?

> Kallmes performs vertebroplasty, a surgery he has helped to develop and standardize, that involves injecting medical cement into the fractured bone to stabilize the fractured area and relieve pain. He says he gets great results from his patients, and teaches the method to other doctors at conferences.

> But here’s the thing: he has no idea why vertebroplasty works. So a few years ago, he decided to test it against a placebo. Kallmes found that pretending to perform vertebroplasty – making it seem like he was injecting a needle into the spine but without the cement – had similar effects. About 40 percent of both groups experienced immediate relief from pain after the surgery. He published his results in the New England Journal of Medicine.

https://www.wnycstudios.org/story/real-doctors-fake-medicine...


Thanks for sharing. Adding another podcast anecdote here — one that made me chuckle — from Scott Belsky in his interview on Tim Ferriss' podcast:

> I remember my father, as an orthopedic surgeon, when he was a resident, he was working in one of those crazy, New York City hospitals where people would come in with like overdoses and shooting wounds and stuff like that. And he was telling me that the most often kind of prescribed [medicine], especially on the psychiatric stuff that came in, was 100cc of Obecalp, which is, of course, "placebo" spelled backwards. And how as soon as someone would be like, "Obecalp, stat, 100cc," that would, suddenly, switch something in a lot of these patients’ minds, in terms of where they felt they were in their hope. And that always stuck with me.


Yes! I did my internship at Los Angeles County-University of Southern California Medical Center ("Big County") in 1974-75. In the ER, it was routine to give repeaters with no obvious source of pain (visits weekly, no other doctor) OBECALP BLACK. These were humongous (about 1" long x 0.5" diameter) shiny black capsules filled with powdered starch. We'd tell the patient, "These contain the strongest pain med that's legal." Worked more often than not in terms of relieving their pain in the E.R. Till next week...

In such instances, giving a placebo definitely seems better than an opiod, but in my opinion, it definitely isn't helping the patient and is likely hurting them by distracting them from the underlying emotional cause. At least when given repeatedly...

In the majority of those patients, the underlying cause was alcoholism and its myriad complications resulting from a store called Liquor Liquor being located across the street from the hospital.

Liquor Liquor? That sounds like a very healthy and reasonable store to have across from a hospital. Nothing unethical or distasteful there!

The irony was not lost on us. The first thing those patients did after discharge was head to Liquor Liquor. It had a huge flashing colored neon sign — ALL CAPS.

We have a bar here in Phoenix, located almost directly across the street from a hospital, called "The Recovery Room":

https://www.google.com/maps/@33.5240529,-112.1032385,3a,15y,...


  black capsules
This reminds me of the "black capsule", the mythical suicide drug in the original film "MAS*H".

> Is it okay for doctors to lie about placebo treatments if it actually helps?

I mean, their oath is to help people, not to tell the truth, the whole truth, and nothing but the truth.


Oh, no. It’s much more complicated than that. The ethical principle you describe might more clearly be defined as beneficence: acting in best interest of the patient. But what about when it conflicts with another ethical principle,namely autonomy: the right to decide what happens to your own body and what treatments you don’t get.

To my mind, there isn’t an obvious answer, but the conflict between these two is why there is debate about “using” the placebo effect as a treatment.


A very interesting ethical discussion I had with a doctor friend recently is that in some cases where a doctor identifies that amputation is the right/only course of action, they will only present that as a soft option to the patient, if at all.

This is because studies have since found that amputations can cause a great deal of psychological harm and it can be better for the patient if they arrive at the conclusion to amputate of their own volition - even if that takes months of excrutiating agony spent realizing not having the limb is better than the pain.

It was an interesting additional dimension to consider - even if the doctor knows much better than the patient, sometimes the patient feeling a sense of autonomy could be important for their wellbeing, and that short term pain could be beneficial.


In some ways this applies to everything we do that we think might be helpful. Sure we could get patients to loose weight by locking them up and only feeding them 1300 calories of veggies, but for some obvious reasons that isn't really an option. We can encourage them to take medications, but they still have to take them.

Atul Gawande talks about how much we have discovered in medicine in the last century, but that the next century is going to be about how to effectively implement that knowledge to help people. This applies to both the first world and to the developing world, though the challenges in both are different.

(also we probably wont stop discovering new treatments that we will them have to deploy...)


> Sure we could get patients to loose weight by locking them up and only feeding them 1300 calories of veggies, but for some obvious reasons that isn't really an option.

Yeah, but a lot of patients would consent to an offered treatment plan where they're locked up (and unable to sign themselves out!) and fed only 1300 calories of veggies.

The weird thing is, there are private businesses willing to provide exactly that kind of service (see: de-tox centers.) But doctors and hospitals generally don't see this as a valid form of in-patient medical treatment. Why is that? Do doctors think that patients have an inalienable right to bodily autonomy? (If so, how would surgery ever work?)

(The annoying point about this difference, to me, is that if a doctor were to diagnose you with X thing that keeps you at the hospital for a month, unable to leave—then your insurance would likely pay for that, and your employer would likely consider you on sick leave. But if a private business like a detox center keeps you for a month, then you have to pay for that out-of-pocket and you're likely to be fired from your job if you don't have the requisite vacation days saved up. From what I can see, it is in the patient's long-term interest if doctors get into this business!)


I figure the ethical debate extends into our societal issue of greed as well. Certain institutions would love to be able to give you no medication/treatment, charge you as though you had received it and you're none the wiser.

Homoeopathy comes to mind.

I am in two minds about it. On the one hand it would appear pretty ridiculous and there is no way that it should be paid for. On the other hand if it works via the placebo effect in a cost effective manner, is that a bad thing?


The placebo effect isnt bad, lying about the effects (homeopathy) charging much more than the cure is worth (homeopathy), and outright selling poison to people (homeopathy) is not ok.

The weird thing about homeopathy is that it's advertised as selling poison, but actually isn't. One of the ridiculous premises is that "like cures like", so it should be poison, but then there's the other ridiculous premise of diluting it to make it more powerful.

except when it is selling dangerous levels of poison:

https://www.forbes.com/sites/brucelee/2017/01/28/fda-toxic-b...


But isn't the lying necessary to be a placebo?

And what is the cure worth? How do you measure that?



How is it supposed to work as a placebo if you're told "hey, this is a glass of fresh water: drink it. And by the way, it's free'.

In other words the lie is integral to the working of the placebo. This is the whole source of the issue.


It does work even without deception, which makes it all the weirder. It's covered in the article.

What's interesting is that it seems to depend on which truth you tell. To oversimplify, "take this, it's not medicine" doesn't help. "Take this, it's not medicine but it will help you anyway" does.

Which is interesting because presumably if they didn't charge you it would shatter the placebo effect. I wonder if cost of the procedure actually impacts the efficacy of the placebo?

Sane middleground:

"We did procedure X, but your insurance covered all of it."


Nobody sane would ever believe that.

Nobody in the Western world outside the US would have any reason to question it.

I'm guessing you're in the US.

Anyone with a decent HMO would, for broad classes of procedures.

They are still providing a service and even pills with starch in them cost something to make. I don't see any reason the doctor and hospital shouldn't charge.


this is a small study - but yes, it appears that way https://www.ncbi.nlm.nih.gov/pubmed/25632091

If it works, its treatment, even the right treatment. Would you know when its safe to give a placebo? That takes diagnostic skill.

If they're just administering placebos do you still have to pay for real doctors?

But then we go deeper into what placebo is. If the patient needs the psychological comfort of being seen and OK'd by real doctors, staying home mentalizing their own well-being won't do much. It's about taking responsibility for self-care--to the extent possible, of course--as opposed to externalizing any ill state to a sanctioned (sacred?) pill.

I think placebo can be self-administered. I can make many pains decrease in intensity (or sometimes go away) just by thinking about it.

Last year I fell while mountain skiing and was in great pain at first (could barely move, standing up from lying down was excruciating, etc.)

The first day I didn't take any pain killer; the second day I did but it didn't really help. The third day I stopped taking the pills and just kind of "decided" I wouldn't suffer that much.

The pain didn't disappear completely, and it still hurt too much to get back on skis, but it stopped being so intense. When I got back home I did an x-ray exam and MRI and found I had broken a vertebra in two, that had lost 25% of its height. The doctor was super surprised I could walk normally and said: "do you not feel pain". I said I did but it was very manageable. She didn't investigate and just said "ok then, good for you!"

Also, I used to get hiccups that lasted a long time (30 minutes); and then I discovered you can make them stop very fast by being super calm and concentrating. Not only that, but since I found this out, I barely get hiccups at all anymore.

I think we can consciously control much more of our own body than we think, and we're only scratching the surface.


You could train actors to give out placebos for a fraction of price. Less work for doctors and more jobs for actors. It's a win-win.

IMO the power of the mind and attitude is really key to how people perceive and function with pain. I don't think that we adequately understand it.

We see that all of the time... I recall working in a bakery in the mall in high school and chatting with a Vietnam veteran with chronic pain from a lung issue and a missing leg who would walk 8-10 miles on crutches every day at 5AM and sometimes do push-ups in our cafe area. He was the most positive person that I have ever met, which was striking when you'd see other folks with very minor issues grouse and complain and be visibly ill.

My mom was taught "therapeutic touch" in the 1960s in nursing school, which I believe isn't considered pseudoscience today. For certain types of patients, it was helpful, but the technique was mostly placebo.

Fundamentally, changing how people think is ethically problematic if it becomes manipulative, but it's a key factor for our well being as well.


> We see that all of the time... I recall working in a bakery in the mall in high school and chatting with a Vietnam veteran with chronic pain from a lung issue and a missing leg who would walk 8-10 miles on crutches every day at 5AM and sometimes do push-ups in our cafe area. He was the most positive person that I have ever met, which was striking when you'd see other folks with very minor issues grouse and complain and be visibly ill.

This might simply be that the Vietnam veteran happens to have much better and more stable chemistry than people with, say, depression.

It seems one danger with this placebo discussion is that we may end up at square one, blaming depressed/anxious/ADHD/BPD people for their problems...


Absolutely... every question seems to open up a minefield of ethical problems, fraught with unknowns.

I suspect that much of this issue is resolved by looking at how they sought consent for their study, since they had to inform participants about what they were going to do to them (though they could have phrased it as, I may do A, or I may do B).

Now, they can say, "I may do A, and I may do B, and there is evidence that both are effective"


Autonomy isn't a meaningful principle when it comes to medicine. Even patients who are doctors can't really give informed consent since they won't necessarily be knowledgeable in the specialty relevant to their treatment. And the vast majority of patients aren't doctors.

Not to invoke a slippery slope argument, but there are a lot of really horrible things that have been done without giving patients autonomy. We as a society need to consider it extremely carefully before any instance of acting against a patient's bodily autonomy.

It would be interesting to compare that against the horrible things people do because they do have autonomy.

If horrible things are being done to people, I'd pick the ones those people are doing to themselves almost every time over the ones being done to others in violation of their bodily autonomy.

The whole point of autonomy is that there is an ethical difference between doing something to yourself, vs. doing something to someone else.

Yes. Obviously you'd narrow things down and compare like to like. Anti-vaxers being the hot example of the day. Sometimes it's so obvious that we act on it, like with secondhand smoking, but I bet there's a lot more to dig into.

Autonomy means that you get to consent (or not) even if you are not informed.

Right, that's the problem. The fact that doctors must ask for the consent of people who don't understand what they are consenting to.

The idea itself isn't that controversial - age of majority laws for contracts, voting, and even medical treatment clearly acknowledge the idea that some people are too young to know what they are agreeing to, so the decision should be made by someone else who takes responsibility for them (most things), or there should be no decision because there doesn't need to be one (voting).

We just need to refine our understanding to reflect the reality that as old as you may get, you will never understand some things.


Autonomy is not a problem of medical treatment, it's a fundamental principle of an ethical society.

Without autonomy, the concepts of voluntary/involuntary lose meaning, which can enable some very nasty scenarios. Exceptions to autonomy are rare and come with stringent legal duties and obligations on the responsible party. Doctors are not responsible for their patients in that way; they are service providers.

Lack of understanding should not be sufficient to undercut an ethical principle like autonomy. Imagine if I had the power to decide that you don't sufficiently understand the concept of autonomy, and must be shipped off to a re-education center.


> Autonomy is not a problem of medical treatment,

Talking about it outside of the specific conflict, is disingenuous. Everyone understands how important Autonomy is. That's part of the issue, not a supporting argument to value it over the health of a patient. If there's no patient, there's no Autonomy either.


The GP comment was "Autonomy isn't a meaningful principle when it comes to medicine."

So, I do not agree with you that "everyone understands how important autonomy is."


Not agreeing isn't the same as not understanding.

If I legitimately didn't understand it, it would be right to teach me. That's why we have mandatory schools for children.

The point of autonomy isn't to treat the patient as the most knowledgeable person in the room, but to present the options, all considerations and drawbacks that you're aware of, answer any questions, and then ask them to make a decision. If you think that patients aren't smart enough to understand the implications of drug side effects and weigh the costs and benefits of treatment versus the original disease, then I really hope you're not a doctor. And I really really hope you're not my doctor.

> then ask them to make a decision

You don't see the irony in that, when talking about the Placebo effect? This discussion is about an implicit assumption.


Is uninformed consent meaningful in the first place?

What about pricing and marketing? Is it ok for a doctor to create a new "placibo treatment" and market it as the real deal on late night tv just because some non zero percentage of people will mark that they had improved symtopms. What is the fair price for a sugar pill that the doctors and compaines are empowered to lie about. Ones mind and mindset play a big role in healing the body and we have far more powerful tools for effecting the mind then future doctor's lies and sugar pills. We have therapy, counseling and the love of family and friends. In my mind its all about hope which doctors can deliver to patients far better with smiles and compassion then sugar pills.

> What is the fair price for a sugar pill that the doctors and compaines are empowered to lie about.

$0.

Health care costs have ruined many, and that's frankly unethical. I don't see a point treating the unethical American health care system as a premise in these ethical debates.


Why would you think manufacturing and distributing a sugar pill should cost $0? Many drugs are basically the same cost as sugar and those aren't free. How about $5 for a bottle of 100.

Precisely, what is advertisement and marketing if not creating an incremental value from a placebo effect?

What if it being $0 reduces to placebo effect so that it no longer is effective?


The practice of medicine is at the service of the patient: the doctor should not make decisions for the patients unless he has to: the final say is always from the patient.

If the doctor lies to the patient, the patient cannot make a proper decision for himself.

So yes, it truly is an ethical dilemma.


> is it okay for doctors to lie about placebo treatments if it actually helps?

Well, if it actually helps, is it a lie? A placebo is something intended to have no therapeutic value, generally for the purpose of testing another treatment. Arguably if you intend something to be the treatment then it isn't a placebo. :)


> is it okay for doctors to lie about placebo treatments if it actually helps?

Let's sharpen the question: What if the lie is the treatment?

It sounds to me like the 40% who the placebo helps for have a different, mainly mental, problem than the 60% for whom it doesn't.


Nope. Placebos can work even when you know it's a placebo: https://www.health.harvard.edu/blog/placebo-can-work-even-kn...

I wonder how much of that effect is due to subjects not understanding what a placebo. Would the effect remain if the study population was other physicians or scientists?

I think it's relatively unreasonable to assume that when the study says that participants are informed that they're taking a sugar pill that the participants don't understand what that means, nevermind assuming that no effort at all was made by the administrators to address this fairly obvious issue. If the entire point of the study is testing whether or not patients still benefit when they understand that they're not taking any medication, it seems self-evident that they would be required to ensure their test subjects understand that they're not taking any medication!

From the article, the guy who ran the study apparently still has reservations on this point: "And he can even be disparaging of his own work, wondering, for instance, whether the study in which placebos were openly given to irritable bowel syndrome patients succeeded only because it convinced the subjects that the sugar was really a drug."

It was 40% effective for _both_ groups. Meaning the "actual treatment" might actually be doing nothing.

Yeah, I got that. The injection probably did nothing aside from a placebo effect.

Can you imagine a label on all drugs. "General surgeon reminds: your doctor might be lying to you as part of your medical treatment. This might not be a real drug"

> It sounds to me like the 40% who the placebo helps for have a different, mainly mental, problem than the 60% for whom it doesn't.

It's likelier that the 60% not helped are those who have a different, mainly mental, problem that the 40% for whom it does work.

If the cure comes from strength of mind, then it probably isn't correct to say that those with weaker minds and wills are healthier mentally.


Are you saying no fractured bone pain is physically based?

That seems overly radical. Then again, I suppose all pain is in the mind at some level.


No, I'm not saying that. My comment doesn't even come close to implying that.

Absolutely correct. It's called Münchhausen Syndrome. What "helps" these patients isn't the placebo, it's the attention. (And it "helps" them in the same sense in which the next fix "helps" the junkie.)

> different, mainly mental

What evidence do you have that the placebo effect is 'mental'?


> It also has some really interesting ethical problems, is it okay for doctors to lie about placebo treatments if it actually helps?

Given that it can still be effective even when you tell your patients you are giving them a placebo, I don't think this needs to be an issue (it's a worthwhile thought-experiment nonetheless, of course).


> when you tell your patients you are giving them a placebo,

Patients dont know they are getting a placebo in clinical trials. It's double-blind by design (doctors dont know either which one is placebo or active ingredient).

Since we assume placebo effect is partly psychological, if you tell a patient you are giving them placebo this could possibly lead to worse outcomes.


There have been "open-label placebo" trials, where the patient is aware they're getting a placebo... and it may still work.

E.g. https://www.health.harvard.edu/blog/placebo-can-work-even-kn...


Not saying it does not work. I am saying the effect is probably less.

I agree. Though it's odd that the placebo effect seems to be getting stronger over the years (according to the article) - I would have thought it would have weakened as the concept spread through the public.

Perhaps that serves to emphasise just how little we actually understand it.

I agree that it is counter-intuitive, but I am not making this up! On top of what jsk13 mentioned, the NYT article itself mentions:

> You don’t even have to deceive the patients. You can hand a patient with irritable bowel syndrome a sugar pill, identify it as such and tell her that sugar pills are known to be effective when used as placebos, and she will get better, especially if you take the time to deliver that message with warmth and close attention.


So, it seems to be based on expectancies. The double-blind setup (while really useful in disentangling drug vs treament (i.e. placebo) effects), seems to reduce expectancies. See for example, this paper: https://www.sciencedirect.com/science/article/pii/S030439590...

The tl;dr is that if you lie to people about their treatment, they get better than those who get told they may or may not receive placebo.

Additionally, if you administer naloxone to people in pain trials, it appears to reduce the placebo effect, which suggests that the effect is mediated by endogenous opioids. (Except in IBS for some reason).

Finally, if you tell dentists that they may be administering placebo analgesics to their participants, the participants report significantly higher pain during dental treatment (even though all participants got an active drug).

So, to sum up, its pretty complicated, but the practical takeaway is that you should try to have faith in medical treatments if you want to get better.


> Finally, if you tell dentists that they may be administering placebo analgesics to their participants, the participants report significantly higher pain during dental treatment (even though all participants got an active drug).

Interesting, I had never considered that as a thing to research! But I can imagine it working like a placebo-equivalent of reverse-psychology.


Do you have a reference for the dentist situation, fascinating result.


Are you sure your interpretation is correct? You said

> if you tell dentists that they may be administering placebo analgesics to their participants, the participants report significantly higher pain during dental treatment (even though all participants got an active drug)

whereas the study seems to claim

> if you tell dentists that they may be administering an antagonist to their participants, the participants report significantly higher pain during dental treatment (even though all participants got a placebo)

The latter seems much more believable to me.

https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=%22C...

https://books.google.com/books?hl=en&lr=&id=8UMDAAAAQBAJ&oi=...


Whoops, its been a few years since I read that paper (I did my PhD on this, but finished a few years back). Apologies for the noise, it appears you are correct.

There was an interesting article in the New Yorker covering this as well, for those who want to read more: https://www.newyorker.com/magazine/2011/12/12/the-power-of-n...

> , is it okay for doctors to lie about placebo treatments if it actually helps?

Placebo does not work on everyone. And it's not the best treatment even if you consider it "works somehow". So doctors will provide what work more often than not, hence an actual drug with proven efficacy vs a placebo.


It's good to note that non-placebo treatments don't work on everyone for every problem as well.

It's also interesting to note that it may not be necessary to lie. In a number of studies, placebos have been effective even when the patient is told they're getting a placebo.

Note that "working" is ambiguous. In many disease where the condition is not entirely chronic, there is often the phenomenon of regression to the mean: i.e. you are recruited in the clinical trial at your worst state, and you progressively get to "average better" even if you don't take any drug. that can also partly explain placebo effect in many cases.

Shouldn’t that be controlled for in a trial?

Absolutely. That's why you have a control group which gets a placebo. Then you can test if the medication is more effective than the placebo.

At least that's how it worked until someone looked at the term "placebo effect" and got confused into thinking that's anything other than regression to the mean.


Yes, but if you're specifically studying placebos you should have a control group that gets nothing.

> But here’s the thing: he has no idea why vertebroplasty works. So a few years ago, he decided to test it against a placebo. Kallmes found that pretending to perform vertebroplasty – making it seem like he was injecting a needle into the spine but without the cement – had similar effects. About 40 percent of both groups experienced immediate relief from pain after the surgery. He published his results in the New England Journal of Medicine.

How did he manage not to be sued into oblivion?


It reads as if he conducted a study in which he got informed consent from its participants.

As is, they were told that they'd either receive an injection with the cement or a placebo injection, and they agreed to participate under those terms.


Hopefully that was the case.

I'd like to believe the journal he submitted his findings to has a rule about publishing papers that used unethical means to obtain data.

Probably because he was making an effort to understand the efficacy of his own treatment which any reasonable person would understand to be the opposite of negligent.

If you were a patient who paid for something and didn't get it.. this is malpractice. There's a chance that if you were in the 60% that had no positive effect, you might've had the effect if you had the treatment. A reasonable person would sue, and a reasonable jury would compensate.

I thought testing against placebo was a standard procedure in medicine and without such testing treatments wouldn't even be approved.

Yes, but patients always consent to be randomized to the possibility of being treated with placebo.

> Yes, but patients always consent to be randomized to the possibility of being treated with placebo.

This is false as a blanket statement. For specific categories like Cancer treatments, nobody is given placebo in Phase III for example, because their life/survival is at stake. For such clinical trials you prove the efficacy by comparing with the typical survival in other studies/other treatments (overall survival chart) like this: https://media.revlimid.com/wp-content/uploads/mm-hcp-overall...


Right, more correctly I should have said:

Yes, but in trial where patients may receive placebo, the patients always consent to be randomized to the possibility of being treated with placebo.


in a clinical trial setting or in general? I'm not sure about everyone else, but I sure wouldn't want the possibility of getting a placebo when I'm at the doctors/hospital.

trial only.

you would have to consent.


jonawesomegreen linked to a story about an FDA-approved fake treatment.

Placebos also work when people know they are placebos. No reason to lie to the patient.

My intuition would be that a significant component of the effect is that the patient believes they have been treated. Until we see evidence otherwise, I see no reason to assume that the placebo effect is not weakened by the loss of that component.

I agree with your intuition, but I'm guessing the parent was referencing this: https://www.health.harvard.edu/blog/placebo-can-work-even-kn...

I have seen it. I do not believe that this test (or others, yet) compared known placebo treatments to unknown placebo treatments.

I see. Yeah, intuitively you're almost definitely right.

I'm a big fan of your music.

> Is it okay for doctors to lie about placebo treatments if it actually helps?

People do this all the time, it's called homeopathy


And it's not okay. It's fraud.

Homeopathic products cannot make claims about treating or curing diseases.

To counter some off the off-the-cuff comments here:

These researchers (specifically molecular biologist Kathryn Hall) seem to have found a link between an enzyme called COMT and response to placebo treatments. That is, people with a genetic pre-disposition for lower COMT-production will respond less to placebo effects and MORE to actual drugs whereas for people with higher COMT-levels the opposite holds true.

I think this is a fascinating finding and does a lot to do away with hand-waving explanations of the placebo-effect as 'it's all psychology' (just look in the comments here).

Unfortunately the article ends with a kind of esoteric tone of one of the researchers, in that he believes it would be unfortunate if we did away with the rituals and warmth and caring involved in more esoteric practices completely. I don't really get that: If we figured out why the placebo effect works and we can very effectively treat patients depending on their genetic pre-disposition that's awesome!


The patients that respond to the placebo are the bane of pharma companies developing a new drug. More than one drug trial has failed because the placebo arm has responded. It is so bad that in some trials they will run a pre-trial where everyone gets the placebo and the responders are excluded before the main trial starts.

It would be interesting to see what else COMT levels are correlated with especial religious and social beliefs.


>It would be interesting to see what else COMT levels are correlated with especial religious and social beliefs.

Very interesting indeed! Maybe it's my 'I'm such a rational thinker'-pride, but I guess I'm in the group that doesn't respond strongly to placebo effects. I'd be more than happy to pop a social-wellbeing pill in combination with whatever pill I need to treat my condition. As opposed to Mr. Kaptchuk’s view that it would be a shame if we lost this dependency on other humans and their empathy for healing.


Whoever thought the placebo effect was a ‘trick’?

It’s well established that the mind controls the brain which controls the body. (And the other way around, too). A physiological problem in the mind can cause a chemical problem in the brain which can cause a ‘physical’ problem in the body. Or heal a problem in the body.

Quotes around physical because mind and body are both physical. If doctors are surprised by this it must be because they are still clinging to some form Cartesian dualism.


And yet placebos do not seem to significantly affect objective measures (they do not improve respiratory volume in asthma for instance). Placebos only seem to work when the mind is also in the measurement loop. That's why we wonder if the patient is actually better or we just think they are.

There is some limited evidence that placebos have some actual effect on reducing pain, but it's hard to separate the effects for many conditions.


This is what I always wondered. Most placebo studies work with pain/chronic pain. But can you somehow use the Placebo effect to reduce the duration of the flu? Or other infections? Does a good patient-doctor relationship (article says that this is an important factor in Placebos) promote faster recovery when a virus is involved?

Edit: Although even here, you often need to trust the answer of a patient about their well-being and can’t necessarily pinpoint the duration of the flu to measurable symptoms only.


I am not really sure we can say that the mind is purely 'physical' with conviction. I think to assert that the mind is as physical as the body falls well short of comprehending the complexities of mind that are truly distinct from body.

This article supports a plausible theory that the mind is a complex system and does not define easily as being purely local to the body:

https://qz.com/866352/scientists-say-your-mind-isnt-confined...

I think when it comes to mind/consciousness the humble position is to say "we don't know enough yet". Humans are certainly not so enlightened that we can define ourselves with precision and we should operate in the world with appropriate humility.


For clarity could you please briefly define "mind"?


So in this paradigm mind is to brain what movement is to body?

Hmm, the brain is an organ of the body, is it any more mysterious if "mind", whatever that is, controls the movement of the arm rather than the brain?

If you decide to think of biting a lemon and your saliva glands react, is that any weirder than throwing a ball? If you just think about throwing a ball without doing it your muscles will still contract in "micro-movements" to act out the act of throwing.


The placebo is based on belief. You give a sugar pill to someone and they believe it is something more. That's "tricking them."

And yes, I do think most doctors in Western medicine cling to a form of Cartesian dualism. It's somewhat tempered, but the mind body connection is vastly underexplored.


From the article:

>You don’t even have to deceive the patients. You can hand a patient with irritable bowel syndrome a sugar pill, identify it as such and tell her that sugar pills are known to be effective when used as placebos, and she will get better


I can't point to a source but I remember reading somewhere that the effect is significantly weakened if you tell patients it's just a placebo, although it doesn't vanish.

FWIR it's more about their expectation of effectiveness, if they believe the placebo will be effective then the placebo will be more effective.

Not always true. All you have to believe is that placebo helps, not that it is not a placebo.

https://www.scientificamerican.com/podcast/episode/placebos-...


There's an old story about Neils Bohr. He was out at his lakehouse with his students, where he had a horseshoe over the doorframe for luck. One of them was outraged and asked "Professor Bohr, surely you don't believe in this sort of silly superstition!" Bohr answered "Well of course not, that's absurd. But fortunately, it works whether you believe in it or not!"

Which comes to mind because I know a few people who are quite knowledgeable about medicine, committed to evidence and rigor, and also go to treatments like acupuncture regularly. They all do it with that same sort of winking sense that sure, this probably doesn't work double-blind, but as long as I don't focus too hard on that it'll work for me. One or two have even said that they consciously avoided investigating past "it's not harmful" to preserve ambiguity.

I'd always wondered how well that kind of doublethink could do for placebo, and while this isn't exactly the same I'm excited to find a discussion along those lines.


Much like Aleister Crowley's joke that explains how Magic works:

”Two strangers sat down opposite each other in a railway carriage. One of the men had on his lap a cardboard box with holes in the top. After some time wondering what might be inside it, the second man said, “Excuse me, but I couldn’t help noticing your box. Does it contain an animal?”

The first man smiled politely. “Yes, a mongoose.”

“A mongoose? Where are you going with that?"

“Ah,” the first man replied, “My sister has terrible dreams. She sees snakes everywhere. I'm taking her the mongoose so it can scare them off."

“But how can that work,” the second man said, “Those are imaginary snakes?”

“Indeed,” his fellow traveller replied. “Which is why this,” and here he lifted the top and tilted it to show an empty box, "is an imaginary mongoose.”


That's excellent.

I think it was also Crowley who commented that of course magic can produce light and fire and all kinds of verifiable signs, but that's all beside the point and so the best magicians are indistinguishable from fakers.

I'm sometimes surprised how many people have hit on some variant of this. It's everywhere from the Black Bible saying that its spells work but have no mechanism of action, to the hacker koan about Tom Knight, to the various "haha only serious" faiths like Discordianism and SubGenius. And it seems like quite a lot of very similarly-minded people arrive at it from different direction - I get the sense that there's a certain mindset that's particularly good for maintaining faith and disbelief simultaneously.


I was watching the NOVA episode on placebo and the definitive physiological effects placebo had for depression, similar to SSRI's. I could not help wondering if the sugar in the sugar pills actually did make you feel less depressed and wondered if an experiment could be carried out with something inert.

> A physiological problem in the mind can cause a chemical problem in the brain which can cause a ‘physical’ problem in the body. Or heal a problem in the body.

Unless my particular pathways are different and I respond to placebos differently than another population.

You're not wrong that it's well established that there's some effect, but beyond that, it's barely science until we can map these pathways.

So it's still a 'trick'.


I don't really find this distinction useful - essentially it comes down to definitions. It's not a treatment that is well understood in the way that some physiological mechanisms may be understood, but trick is an overloaded term and the persisting feeling that it is a trick may well be dampening furthering our knowledge in this space.

In any case after studying some pharmacology, my takeaway really was that "understand" is a pretty relative term - biochemistry is insanely complex and medical chemistry is a pretty fuzzy thing when it boils down to it...


It goes both ways, right? The body can create issues that cause chemical problems in the brain.

I'm pretty sure doctors didn't write the article name.

Right, but where did the article come from at all?

Is it a common misconception that the placebo effect is a 'trick'?


> Is it a common misconception that the placebo effect is a 'trick'?

My experience says yes, it's a trick. As in, mind may be over matter but if it's a placebo it's worse than the real thing, or at least that's the connotation I had for the word.


It's a trick as in "all the tricks of the trade" or "does the trick", or "the trick is to keep breathing". It does not necessarily have the negative connotation everyone here seems to pick up on, just as it doesn't involve any tricks being turned, two hours wasted at the helm, games of bridge, or sketchy coats of arms.

(This post sponsored by MacOS' built-in dictionary)


I don't think it's fair to say the mind controls the brain. The relation between the controller and the controlled is reciprocal.

> Whoever thought the placebo effect was a ‘trick’?

People pretending to be journalists who need to clickbait to make money.

I wish the nytimes would stop making their headlines a question already.


Seriously.

It's universally established and accepted that placebo is a legitimate medical effect. That's one of the major purposes of control groups and double blind studies: many medicines don't make it to market because they have a positive effect LESS than placebo.

Clickbait more and more out of NYT. What a world.


Clickbait doesn't mean what you seem to believe it does ("any headline that isn't the least interesting summary of the article").

More importantly, "trick" may also not mean what you think it does.

It's a rather interesting word, actually. Your interpretation seems to focus on the bad aspects, i. e. deception. But a trick can also be a clever shortcut. It might still involve some make-believe, but puts it in service of a good cause.

That's somewhat closer to the intended meaning here. And it's a perfectly valid way to describe the undeniable peculiarity of placebos.


I don't think the point of the article was to say that placebo is a legitimate effect but exploring the philosophy of science implications of the research on placebos the author was reporting on. I'm personally very interested in reading about this sort of stuff and similarly enjoyed their other recent article about Latour but I could also see how someone would think it's non-sense.

Teaching people something that you happen to already know is not "clickbait".

https://xkcd.com/1053/


I find it unusual that many people will dismiss the placebo effect yet will happily accept that stress can cause lots of negative reactions physiologically. They seem like two sides of the same coin to me.

> the rituals embedded in the doctor-patient encounter that he thinks are fundamental to the placebo effect

> “Medical care is a moral act,” he says, in which a suffering person puts his or her fate in the hands of a trusted healer.

I have a friend who is a naturopath, and this is basically what she believes her job to be. Almost more of a therapist at times, a friendly ear to confide in.

The average experience with doctors isn't always that pleasant. It feels clinical and rushed, and very non personal. They are concerned with symptoms, not the actual person in front of them. They don't really listen, as a therapist would. And it's not their job too.

Contrast that with an alternative healer. They will sit and talk and listen and empathize with you for an hour. For a person in pain, it might be the first time they have ever felt like someone actually understands and cares. It's not surprising that they feel better afterwards. I think that goes a long way to explain the popularity of fake medicine.


How does that explain the popularity of shelves full of fake pills at GNC and Walgreen's?

I imagine those are popular because for many problems there are not yet any real solutions.

Got a cold? A muscle tear, connective tissue damage? weird back pain?

There are no definite solutions to those. And ever smart HN person who think they know the solution to that, only knows a thing that they believed worked for THEM and won't necessarily work for ME and may not even have worked for them, it just got better with time and they think it was their special cross fit routine because of chronological fallacy.


The 'placebo effect' seems to be wholly the effect of the sum of biases and psychological effects on reported outcomes in the placebo (non-treatment) arm of medical trials. It doesn't mean there is an 'actual' effect, it is just that reported benefits by patients is affected by the situation. 'The nice doctor gave you pills, and trying to be helpful you might respond more positively when asked if you are any better.' Or 'patients with a temporary flare up in their condition were invited onto a trial, and - lo - they got better even without the active treatment.'

Placebo just refers to the bundled biases and other uncontrolled-for influences. It is not a real thing that can be used to make anyone actually better. Whenever there is a physical measurement that can be made about some affected body function, the placebo effect mysteriously disappears.


I don't know about that. There's also the nocebo effect [1] that is rather well known. You make it sound like "placebo" is purely a bias thing, but AFAIK both placebo & nocebo effects, though presumably psychogenic, can sometimes induce measurable changes in the body.

[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401955/


There’s a great chapter in Thinking Fast and Slow where he talks about how placebo might be only a statistical phenomenon: regression to the mean. Sick people are a statistically extreme group, and tend to revert to the mean over time without intervention.

does that stand up to experiments pitting a placebo group against a control group that gets no treatment at all?

No, it does not. While Kahneman is a wonderful scientist (psychologist, btw), he has this annoying habit of attempting to fit everything into his models. He's dead wrong on placebo, even though regression to the mean is a real thing.

There is research supporting Kahneman: https://www.ncbi.nlm.nih.gov/pubmed/1280801

So while I don't dispute your link (because it's correct), the placebo effect is normally defined as the effect over and above that seen in the no-treatment group (who don't get a placebo or treatment). Regression to the mean would impact both placebo and no treatment (as well as treatment) groups equally, so cannot be the explanation for the entirity of the placebo effect.

Placebo patients know that they have received a treatment, so that introduces a bias in the reporting of outcomes from the patient, even if the medics are blinded. If you believe you have been treated it is well known that patients report improvements even for illnesses that can be measured not to have improved.

The breaking of blinding and contrary measurements is enough to undermine most claims for placebo.


Yes, I agree. That's what the no-treatment group controls for. And generally, both medics and patients are blinded.

I sometimes wonder about the validity of comparison with the placebo. What if the drug being studied makes the patients feel something, but doesn’t directly help the condition being studied. But that something feeling alerts the patients that they’re getting the real drug and not the placebo, and that awareness causes all the psychological biase we’re worried about?

Kahneman is supported by research. https://www.ncbi.nlm.nih.gov/pubmed/1280801

Good luck finding an ethics board who will let you do that experiment on actually sick people.

"Ah, people with pain. One group will get nothing and the other a placebo."


Pretty sure they do that all the time?

Reminds me of the old joke, where a respected scientist is announcing he has some great cure for the disease of the day and is presenting the impressive results to an audience, when someone pipes up and asks:

'How did this compare to the control group?'

The presenter is indignant and says, "Excuse me? You're asking if I randomly selected half of these poor souls to be deprived of the medicine, just to see what would happen to them?"

'...yes.'

"Of course not! That would have condemned half of them to an avoidable death!"

'...but which half?'


I love this. It's not even a joke really.

so do it with the common cold or something equally untreatable/fairly harmless.

not that I was proposing such a study - I was asking if we have already done them and what the data says if we have.


Don't you think it is intriguing that the placebo effect only gets reported for non-specific subjective complaints, and not physically measurable ones?

This article lists a few physically measurable changes caused by placebo:

https://www.medicalnewstoday.com/articles/306437.php


WhyDontPlacebosRegrowLimbs.com

(Not a real site, just riffing off whydoesntgodhealamputees.com.)


No, it cant be just that. We know for example that lack of social support causes increase in pro inflammatory cytokines, among other real effects. It would be highly implausible for the placebo effect to not be rral.

I don't see the distinction. If you think you feel better you do feel better, doesn't matter why. However, unlike some, I do not think this justifies the use of nonsense medical practices. You can be kind and caring to the patient and NOT sell them kinesio tape or wathever.

The fundamental question here is simple. To what extent can the mind affect the body? There can be no argument that the mind has at least some effect: a straightforward example is mood and blood pressure. For now, let's assume that this extent can be large.

Following is the assumption that, while we have learned a lot recently, the total map of mind/body connections is enormously larger than our current understanding of it.

So, it seems possible to me that the placebo effect can have real, physical and measurable effects on a human body, given the above assumptions.

One way or another, decades of research of, to varying degrees, confirmed this connection, though we haven't made much progress in understanding the underlying mechanisms of action.


I strongly believe that, "placebo" effect is probably just contextual effects. There is an experiment (I don't remember the name) with 4 cases:

- A placebo pills and a nice, empathic, optimistic doctor - No pills and a nice and empathic doctor - A placebo pills and a cold and pessimistic doctor - No pills and a cold and pessimistic doctor

The pills have practically no effect at all, doctor behavior can have a measurable impact.

Besides I don't think there is a proven effect of placebo for other than psychosomatic symptoms (in particular pain and depression symptoms).


I would take the time to closely read the article. It points to several cases where the placebo effect went beyond psychosomatic, specifically treating irritable bowel syndrome and preventing heart disease.

> Whenever there is a physical measurement that can be made about some affected body function, the placebo effect mysteriously disappears.

What matters is not that subjective feelings do improve?


The claim is that physical ailments improve, which isn't true if there are physical measurements takes.

Well apparently there are physical measurable effects, as another poster commented below.

https://www.medicalnewstoday.com/articles/306437.php


It depends what you have. I don't want to feel great if I still have terminal cancer. I want it cured.

With the exception of pain

I don't think pain can be measured reliably at all, nor can it be reliably communicated.

It's such a shame that the two scientific fields that we desperately need to advance, psychology and neuroscience, often need to rely on purely subjective input.

How is it a shame that solvable problems are solved before unsolvable problems? The alternative would be NOT solving solvable problems.

Not sure how you construed that from my response, but regardless, I'd argue that tackling the "unsolvable" problems is still a worthwhile pursuit. The alternative would be not discovering germ theory or quantum mechanics (well, more relevant examples would be the realm of philosophy and psychotherapy).

How would it ever be any different? You can't really remove subjectivity from the measurement of people and their brains.

Just because we can only measure something subjectively right now doesn't mean that we won't be able to measure it objectively in the future, unless of course we don't bother trying.

One trick is to figure out if there are any objective measurements that can be taken which line up with the subjective input. One example is taking an EEG recording while performing a backward-masking experiment (aka displaying subliminal images), and seeing if their subjective experience "I did see the second image" versus "I did not see the second image" line up with the EEG measurements in the prefontal lobe.

https://www.amazon.com/Consciousness-Brain-Deciphering-Codes...


I'm not sure if we can actually localise particular EEG's that precisely. In any case, that just punts on the problem - subject reports they did or did not which we use to make an assessment. We still rely on subjectivity.

Like, I really don't see any way of avoiding this in psychology and neuroscience (and indeed even if possible, it might not be a good idea).


But we can localize it that precisely, and cheaply. In that particular experiment, they found that the areas of the brain that are commonly associated with raw visual input activates precisely whenever an image appears, subliminal or not. Then a large, delayed negative wave reliably appears in the frontal lobe only when the patient affirms that they saw the image. It's using objective methods to confirm the subjective.

These sorts of experiments are helping with making prognoses of whether a patient recovering from a coma will remain in a vegetative state, or if they'll regain consciousness in time.


Do you happen to have a paper link, rather than a book link?

Sure, I don't have the book on me, but this journal entry (written by the author) in Neuron outlines the main points raised here with plenty of references/citations to back it up. https://www.sciencedirect.com/science/article/pii/S089662731...

I suppose if you're a staunch Behaviourist you can say that

It gets quite strange:

A prominent placebo researcher, Dr. Fabrizio Benedetti, was able to show just how peculiar the placebo effect really is. After inducing pain in participants for seven days whilst treating them with morphine, Benedetti secretly switched the pain medication to salt water. Luckily for him, the participants’ reports of pain went unchanged. Then things got weirder. Benedetti didn’t want to stop there, so he [secretively] gave the participants a morphine blocker and, bizarrely, the participants found that their pain returned, suggesting a form of biochemical reaction to the salt water placebo.

So you give people morphine and it works (to block pain). Switch it secretly with salt water and it still works. Secretly add a real morphine blocker and it no longer works. Bizarre.


A possible explanation could be that the body gets the "hint" that morphine blocks pain, and starts to make its own; then when you administer the morphine blocker, it doesn't react with salt water but with the body's morphine (or equivalent).

> suggesting a form of biochemical reaction to the salt water placebo.

I know this was a quote from the article, but... Does it really suggest that? Isn't it possible something else is going on?


Could it be that this morphine blocker is blocking endorphins?

https://en.wikipedia.org/wiki/Endorphin


Wow.. so the body somehow chemically "flagged" the salt water as morphine? That's bizarre.

The headline reminds me of my high school math teacher that would say that the difference between tricks and methods is that methods are tricks that have been used more than three times.

By the same token, it's only a trick as long as the underlying mechanism is unknown.


I had a really hard time with medical anxiety after my dad almost died from pancreatitis suddenly. Stomach pains, heart palpitations, numbness in various places. I was convinced I had 10 different fatal diseases. I wasn’t making up symptoms. I had real pain, a chronic cough, and real pvcs that showed up on ekgs. It took a lot of doctors and a lot of tests to convince me that I was okay. And then i started to understand that all of my symptoms matched a single disease— “anxiety”. And I started focusing on letting things go and not thinking about it and avoiding triggers like caffeine and all of my symptoms just ... stopped. A miraculous cure of like 10 different things I was utterly convinced I was dying from. Even the pvcs and my non-stop post nasal drip stopped almost entirely.

The body is fucking weird.


"Scared to death" is not just an expression, as your case perfectly illustrates.

There's a general tendancy to discount the matters of the mind when treating the body, but both are very much connected and usually for a good reason—at least from an evolutionary perspective. In the US, there's often a stigma associated with just admitting weakness. Support exists but it's not always easy to come by.

It helps a lot if you can find a Primary Care Physician who has at least some notions of psychology and can help bridge that gap—and if needed, recommend the help of specialists regarding our thought processes. (In your case, it sounds like you were on your own to figure this out: glad it worked out, though!)


Similar here: had chest pain, heart palpitations, racing pulse, shortness of breath, dizziness etc. for more than a year. The pain and dizziness was real and worrying. Was convinced I was going through heart failure in my 20s. Took a while to get an appointment with a cardiologist, but I got it and he did a few tests, said "it's just stress" and from that moment on the symptoms essentially disappeared. Boy was my face red (from face disease, I believe).

Interesting. Have you seen the Afflicted series on Netflix? Do you think they're experiencing a similar thing?

What's the most impressive placebo effect recorded in a study? Is it always limited to mild pain relief?

For stories like this, people always predictably discuss how ethical it is for doctors to knowingly prescribe placebos for stories and how different interventions have different impacts.

If placebo alone can't cure anything and only gives mild pain relief, I'm surprised nobody mentions it's overhyped.


I'm still reading the submitted article, but with the many relevant useful comments of `tokenadult in mind: https://hn.algolia.com/?sort=byPopularity&prefix=false&page=...

> Placebo effects are strongest for patient self-reported subjective symptoms (classically, pain) and weakest for objective clinical signs measured by experienced observers.


Do you have a specific example of a very strong placebo effect though that's beyond patients reporting mild pain relief?

My point is people seem to discuss placebo with an implied assumption that the effect is so big it's worth e.g. discussing the ethics of prescribing it. If it's only giving mild pain relief I don't see why it's that interesting.


All of Homeopathy? It operates on the principle that a cold when untreated will last 2 weeks, but with placebos will only take 14 days.

Ugh. It's so disappointing to see this comment from someone who clearly didn't read the article.

And you're misrepresenting Homeopathy--that's not the principle on which it operates.


For my money, the most impressive placebo effect ever is the purported improvement in athletic performance using Breathe Right Nasal Strips. The inventors have made many millions of dollars by cleverly repackaging and reframing adhesive tape. See, for example: https://www.sciencedaily.com/releases/1998/06/980609080557.h...

That’s not the placebo effect if it doesn’t actually improve performance... it’s just delusion.

I'd say this is really impressive: sham surgery on the meniscus.

https://fivethirtyeight.com/features/surgery-is-one-hell-of-...


> Arthroscopic knee surgery has been a common orthopedic procedure in the United States, with about 692,000 of them performed in 2010,2 but the procedure has proven no better than a sham when done to address degenerative wear and tear, particularly on the meniscus.

Isn't this just showing the supposed real surgery doesn't work? I don't see how this is showing placebo has an impressive effect.


It shows both.


The most impressive placebo effect is it's effect on placebo researchers and science writers.

Pseudo pregnancy, where mind plays tricks, producing all pregnancy symptoms. Even transexuals get it.

> Even transexuals get it.

To be honest, we are actively hacking our body when using hormone replacement therapy. Strange things are bound to happen. Skipping a dose of estrogen can trick the body into triggering PMS like symptoms, etc.


Does anyone know of a study that finds an actual placebo effect?

As far as I can tell, there are two distinct effects, and both are meaningless. The first "placebo effect" is observed everywhere, and is simply reversion to the mean. Nobody studies a treatment on healthy people, because treating people for a condition they don't have makes for a very expensive study. But some of those people get better spontaneously, and some weren't even sick, but had the right symptoms. Their improvement without actually being treated was originally called the placebo effect.

The other "placebo effect" is the one where treatment with a placebo (preferable an expensive placebo labelled "forte" and administered by the chief of medicine) is more effective than no treatment. But that effect only happens where the only way to measure the outcome is by asking the patient. A human is a very unreliable instrument. A human may report that the irritable bowel is gone because he doesn't take the symptoms as seriously anymore after the treatment, or maybe because he just wanted attention and there had never been an irritable bowel.

So, does anyone know of a study that finds a placebo effect that isn't explained by "bad instrument" aka. self reporting?


Reversion to the mean is not the placebo effect. The placebo effect is what you're calling the "actual" placebo effect, and in many cases produces objectively measurable results, which is why they need to account for it in drug trials: you compare both the drug and the placebo to the control group and see if the drug exceeds the placebo. As far as I know, practically every such drug trial validates that the placebo effect is real.

You're wrong, at least according to Wikipedia. But I don't want to argue semantics, I just want one study that shows a measurable (not self-reported) effect. Just one. Please?

https://www.ncbi.nlm.nih.gov/m/pubmed/1286471/

Retrospectively analyzes patients who got placebo, vs natural course patients. Placebo group fared better in physical exercise compared to the natural course group.


Has anyone studied whether there is an opposite anti-placebo effect? Like if a patient lacks confidence in their doctor and doesn't believe that a real medicine will actually work, is it less likely to be effective?

That sounds like the nocebo effect maybe? From the Wikipedia page [1]:

> A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have.

[1] https://en.wikipedia.org/wiki/Nocebo


Yes, it's the nocebo effect. I personally think it figures prominently in psychosomatic pathologies actually.

People with [psycho]somatic symptom disorders, with medically unexplained symptoms, are more likely to report negative side effects in response to placebo, for example.

When I've read about it, the research is often focused on perceived negative symptoms rather than lack of therapeutic effect, but that's just my impression and I suspect both happen.


There seems to have been some research around the "nocebo" effect.

https://en.wikipedia.org/wiki/Nocebo#References


"Open label placebo: can honestly prescribed placebos evoke meaningful therapeutic benefits?"

"Results from small clinical trials suggesting that placebos can be ethically and effectively used in clinical practice warrant further study, argue Ted Kaptchuk and Franklin Miller"

BMJ 2018;363:k3889 doi: 10.1136/bmj.k3889 (Published 1 October 2018)

http://media.virbcdn.com/files/01/147bb1aea3d8c05b-Kaptchuk-...

"Key messages:

- Placebo pills in randomised trials can significantly benefit patients’ subjective symptoms

- Using placebo pills clinically is an ethical challenge as prevailing wisdom asserts that deception or concealment is required

- Recent small randomised trials suggest that openly prescribing placebo can evoke meaningful therapeutic benefits

- More research is required to determine the role for open label placebo and the conditions in which it is effective.

"


From what I have understood, the Placebo effect is the most thoroughly studied medicine, with millions of real test cases.

Nobody investigated the why like this - the two scientists followed most prominently in the article possibly found a genetic marker for high and low responders to placebos, partly because those two had the background and experience with placebos working in acupuncture from professional work and treatment and the expertise to investigate.

It isn't a trick. It's why pharmaceutical trials have a placebo control, not a nothing-control.

There's been studies done on the effect of different placebos: bigger pills, with bigger markings, administered by professionals in professional settings etc work better.

My pet theory is that, since almost all medicine merely assists the body's own healing (e.g. a plaster cast doesn't heal the bone), the belief of safety and being looked after is enough for your body to switch resources away from dealing with a threat towards healing. (You can't afford to heal while your attacker is still around.)

A placebo signals safety.


IIRC, it was more or less the idea developed by Dylan Evans in "Placebo: Mind over Matter in Modern Medicine".

I believe that placebo-like effects extend to other areas of life, outside of health. Tell people that they are victims of some historical injustice or discrimination and such, and these victim's beliefs will keep people from advancement to their best capacity. They genuinely can't advance. Similarly, in situations of domestic abuse or sexual abuse: whatever happens on psychological or biochemical level, keeps these people down, genuinely unable to properly recover or move on.

Seems to me that attitude is 90% of success in this world...


I would love to see some more advanced psychological manipulation experimental results for medicine ... “I proscribe you to not take this pill twice a day. By that I mean, here’s a bottle of pills which have been shown to alleviate your ailment, however I believe your case is best addressed by you deciding not to take this medicine. Therefore, twice a day, please follow these directions: remove a pill from the bottle, place it in your hand, look in the mirror and then put back in the bottle and close the lid.”

Many Trippy effects are possible.


I'm currently reading "The Biology of Belief" by Dr. Bruce Lipton and feels very relevant.

Can anyone help me figure out if I'm of the variant of the rs4680 allele that is most placebo respondent if I have my 23andme results (I am variant G)?


https://www.snpedia.com/index.php/Rs4680

(A;A): (worrier) advantage in memory and attention tasks

(A;G): Intermediate dopamine levels, other effects

(G;G): (warrior) multiple associations, see details


A;A = placebo more effective G;G = placebo less effective

Thank you!

I had a psychologist tell me about a case once where a person had a condition (I forget which, I think it was mild diabetes) but only when they were living at home with their family.

They tested positive for this condition. It wasn't all in their head. But then again it was in some sense. They spent time away from their family and their condition would stabilize to the point that they'd no longer test positive. I asked about things like diet and sleep and the guy telling me the story said that this was of course the first thing they checked and the person's diet and sleep habits hadn't changed.

The psychologist who told me this story wasn't particularly "woo-woo" and was personally blown away by it. He said you can find other cases like this in the literature.

Anecdotes like that aren't proof, but they're interesting in that they agree with some of this placebo effect research. It looks as if the brain has more influence over the body than we realize or understand.


VS Ramachandran's Phantoms in Brain (p.224): "A second example of a genuine anomaly is multiple personality dis­ order or MPD, which in my view may turn out to be just as important for medicine as continental drift was for geology. To this day MPD con­tinues to be ignored by the medical community even though it provides a valuable testing ground for the claims of mind-body medicine. In this syndrome-immortalized by Robert Louis Stevenson in Dr. Jekyll and Mr. Hyde-a person can assume two or more distinct personalities, each of which is completely unaware, or only dimly aware, of the others. Again, there have been occasional reports in the clinical literature that one personality can be diabetic while the other is not, or that various vital signs and hormone profiles can be different in the two personalities. There is even a claim that one personality can be allergic to a substance while the other is not and that one might be myopic-or nearsighted­ whereas the other has 20/20 vision."

Something interesting is that numerous studies have shown that a number of psychotropics, including the monstrosity that's fluoxetine/prozac, perform at levels that is hardly better than placebo. In many cases the difference is not statistically significant. This [1] paper/article provides an overview of a variety of data. It also goes into how these sort of drugs manage to get approved in spite of negligible performance. The paper gives the example of vilazodone/viibryd. That drug went through 5 trials. They showed absolutely 0 effect. In some of the trials the placebo outperformed the drug. Undeterred, the company continued running trials. In the next two they managed to show a very small effect, probably similarly to how if you flip a fair coin enough eventually you'll get heads 10 times in a row 'proving' the coin isn't fair. Anyhow those two trials showing a minuscule effect were enough for the FDA which now states, "The efficacy of VIIBRYD was established in two 8-week, randomized, double-blind, placebo-controlled trials.".

I find this just completely fascinating. That prozac shows a negligible effect over placebo in blind studies is even more interesting to me because of the side effects. It has some really serious side effects - you'd know if you were getting the 'real' stuff, at least if you were allowed to communicate with the others who were. And the prozac brand alone was, at its peak, reaching profits of $2.6 billion a year. This creates a nasty incentive for pharmaceutical companies to target 'drugs' at conditions that can be treated by placebo. Because in these cases, you can always prove the drug works, without actually having to go through all that nasty work involved in creating a drug that actually works.

[1] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172306/


It's important to note that placebo effect does not work at all on stuff like infectious diseases. There are clear categories of diseases where your psychological state will have absolutely close to no influence on the outcome.

You also can't use a placebo for euthanasia, it doesn't work. You also can't suicide by overdose with a placebo. (plot point in a short story I drafted a while ago).

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