Gary Greenberg on the Placebo Effect
Feb 4 2019

placebo-effect-200x300.jpg Author and psychotherapist Gary Greenberg talks with EconTalk host Russ Roberts about the placebo effect. Is it real? How does the placebo effect influence drug testing? If it's real, what is the underlying mechanism of why it works and how might it be harnessed to improve health care? The conversation concludes with a discussion of how knowledge of the placebo effect has influenced Greenberg's psychotherapy practice.

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Explore audio highlights, further reading that will help you delve deeper into this week’s episode, and vigorous conversations in the form of our comments section below.

READER COMMENTS

Merrijane
Feb 4 2019 at 10:14am

I’d be interested in whether pets like dogs and cats respond to placebo affect since they don’t often understand what medical care is for and usually never have a positive vet experience.

Pete Miller
Feb 4 2019 at 12:17pm

I’ve paused listening to this episode because it took me back to one of my most vivid classroom memories from my undergraduate years at the University of Chicago.  I was taking Self, Culture, and Society, one of the common core social science courses which led me to change my major to behavioral science.  The professor that quarter was, if I’m remembering correctly over 37 years, Mark Krug; and I can’t remember what reading or topic we were discussing, but he shared this anecdote.  He told us he had been experiencing a mysterious pain in one of his shoulders, so he made an appointment with his doctor who spent a few minutes with him and thumped him on the back asking him to rotate the joint into various configurations and report how painful each one was.  At the end of the consultation, the doctor gave him a diagnosis of bursitis, which immediately made him feel better and more in control of the situation.  A few days later, Dr Krug was chatting with a friend who taught at the medical school and related the story to her including how much better he felt just having a name for what was wrong with him.  His friend laughed and asked him did he know what bursitis was?  Dr Krug admitted that he didn’t, and she replied that it meant he had a pain in his shoulder and the physician didn’t know what was causing it.  He used this as an example of the power of putting a name to a concept as a way to exert control over the phenomenon that could be both useful and deceptive.  He suggested that we strive in life to take advantage of that power in such situations, but always scan for the deception as well.

Danny Kao
Feb 4 2019 at 4:01pm

I’ve noticed during my 3 decades as a physician that, for the right patient (data driven “engineer” type, etc.), a no-nonsense, just-the-facts, “low empathy” doctor results in GREAT interpersonal rapport and consequently, strong placebo effect.  Even a physician with “poor bedside manner” can have fans 🙂

Richard Fulmer
Feb 4 2019 at 5:40pm

Dr. Greenberg talked about an enzyme produced by people with that extra DNA strand that seems to enhance the placebo effect.  Obvious questions: What is that enzyme?  Is anyone studying it?  Are there ways to synthesize it? Might it have medical benefits?

Marilyne
Feb 4 2019 at 7:45pm

This 2017 Vox article on the placebo effect provides an excellent summary of how it works, much in line with what Gary Greenberg describes:

https://www.vox.com/science-and-health/2017/7/7/15792188/placebo-effect-explained

Jordan Miller
Feb 4 2019 at 7:51pm

Very interesting discussion. As a Christian Scientist–someone who believes all disease is basically a mental phenomenon and the symptoms of disease are mental pictures that can be eliminated through communion with a Higher Intelligence—it was exciting to read Dr. Greenberg’s article in the NY Times, which validated a lot of what we’ve been saying for over 150 years.

We share Dr. Greenberg belief in “secret radio waves” but we call them spiritual laws of God which can be invoked mentally.  Perhaps one day he might like to test them…

 

Simon Whyatt
Feb 5 2019 at 8:03am

Please get an actual expert on to cover this topic again.

Perhaps someone from the Science Based Medicine website.

First major blunder, there are various placebo effects, plural.

Second,  while very interesting and important , they are not nearly as magical or powerful as Dr Greenberg seems to believe .

Third , we know this because placebo effects have been studied extensively .

I again emplore you to do another podcast on this topic, as it is fascinating, but with a genuine expert .

Sean Wordingham
Feb 19 2019 at 3:26am

I would like to add my voice to Simon’s.  Please get an expert on to talk about the placebo effect.  Dr Steven Novella would be great, and could also comment on the issues with epigenetics and evolution that came up in the following podcast.

I found it particularly strange that Gary Greenberg gave cancer as an example of something which the standard model may not be useful for, since cancer is a condition that shows little to no susceptibility to placebo effects, while standard medical techniques have enabled people to live far longer, better lives with cancer.

Michael McEvoy
Feb 5 2019 at 10:00am

I have not finished the entire discussion but there is a cogent and contrary argument . See

https://sciencebasedmedicine.org/are-placebo-effects-genetically-determined/

Central to Dr Gorski’s argument , as I understand, is the distinction between REPORTED improvement and MEASURED improvement from placebo. I believe your guest either denies or simply fails to recognize this distinction .

Of course the randomized DB Placebo controlled trial is terrible in many respects . But it is like democracy, it is better than all the alternatives .

Russ, I am worried you want to throw the baby out with the bathwater. ( I am thinking of your prior explicitly stated stance on PSA ) .

Perhaps you could get Dr Gorski as a guest . He has thought a great deal about medicine and continues to work in it.

Blackthorne
Feb 7 2019 at 12:06am

I don’t really think Gary Greenberg fails to appreciate the distinction between reported and measured improvement in the way you mention. I listened to the episode on Monday so it’s been awhile but if I remember correctly all the situations they described were ones where you care more about the reported response than the measured response. Maybe the IBS example isn’t, but I’m not knowledgeable enough on IBS to really comment on that.

I read through your link and I was wondering if you could answer some questions for me. For a condition like chronic back pain, does it really matter whether the method someone uses is grounded in science or can be replicated in an experiment? Is the worry that by selling the placebo effects for more than what they really are, we’re going to wrongly encourage individuals to substitute away from science-backed “western” medicine? Or is the idea that this placebo effect may make someone feel better but it won’t address the underlying issue causing their condition?

James M
Feb 7 2019 at 3:40pm

I think their primary concern is that overselling the placebo effect is unscientific. It doesn’t help us understand what is actually happening. I can advocate magical spells for back pain but we’re not interested in whether or not people feel better after the magic spell; we’re interested in whether or not it’s the spell specifically that makes them feel better. The placebo effect, by definition, is non-specific so any benefit derived from that doesn’t give us insight on what is going on.

Of course, patients feeling better is the end goal. But by what standard are we supposed to critique potential treatments except by whether or not they are grounded in science and able to be replicated in a lab? I don’t know a better method.

And then, as you mention, I think they are concerned with some of the downstream effects of unscientific treatments, e.g. the opportunity cost of wasted time, money, health, etc.

Don Crawford
Feb 23 2019 at 2:00pm

Here is Dr. Gorski’s analysis of the milkshake study in this article: https://sciencebasedmedicine.org/are-placebo-effects-genetically-determined/ .

Another of my pet peeves aside, I hadn’t seen the milkshake study before. Reading the actual study, I was less impressed. In brief, on two separate occasions, participants consumed a 380-calorie milkshake under the pretense that it was either a 620-calorie “indulgent” shake or a 140-calorie “sensible” shake. Ghrelin, a gut peptide mediating the sensation of hunger, was measured via intravenous blood samples at three time points: baseline, anticipatory, and postconsumption. During the first interval participants were asked to view and rate the (misleading) label of the shake. During the second interval (between 60 and 90 minutes later) participants were asked to drink and rate the milkshake. The mindset of indulgence was reported to produce a “dramatically steeper” decline in ghrelin after consuming the shake, whereas the mindset of sensibility produced a relatively flat ghrelin response. Looking at the paper, I saw several problems. First, although the participants didn’t know that both shakes were the same, it’s not clear whether the investigators were blinded at each session. Second, the “dramatically steeper decline” is less dramatic than presented. There are no error bars on the “money graph” to show variability, and the p-value of the repeated measures effect was only 0.04. Third, the authors did some truly annoying data presentation, showing the X-axis only between 880 and 960 pg/ml, with the final values differing only by around 20 pg/ml, or around 2.2%. In other words, this was a small study with a small effect that was barely statistically significant. Quite underwhelming, and the authors barely mentioned placebo effects, although in the last paragraph they did liken their findings to them.

Doug Iliff
Feb 5 2019 at 4:50pm

As a family physician for 40 years, I treat two general kinds of problems.  On one hand, there are things I can measure or observe objectively: dyslipidemia, hypertension, diabetes, fractures, deliveries.  Then we have disorders which may have observable components, but are primarily subjective: depression, joint pains, headaches, sore throats.  We all understand the difference.  Dr. Greenberg, being a psychotherapist, deals exclusively with the latter, and it is these disorders which are most subject to the “placebo effect.”

“The doctor is the drug,” I was taught in medical school, and there is a lot of truth in that; therefore it is important that I tailor my personality to my patient, so that the care which I really feel is imparted to them.  It is also important that I remain up to date with the most objectively measurable, cost-effective therapeutic measures, whether or not they have a significant placebo component in clinical trials.

Therefore, in day to day practice, the placebo effect rarely enters my thought processes.  However, Russ’s story about his ultrasound-guided shoulder injection brings up an ethical point.  I do a lot of shoulder injections, and ultrasound guidance is unnecessary.  So why do it?  I can venture a suggestion.

For many years I suffered intermittently with a Morton’s neuroma, a swelling of a nerve at the base of the interspace between the third and fourth toes.  I would inject myself with a steroid and get relief for six to twelve months.  Finally I went to a podiatrist, who did the same thing with ultrasound guidance.

It didn’t do any better than my injections (I finally had the nerve  surgically removed last fall) but the ultrasound guidance was billed at $750.  Remember, now, this is a spot you can’t miss; a blind man could inject the right spot by feel alone.

Apparently Russ didn’t see the bill for that component of his procedure, but whatever the charge, I would submit that this is an ethical problem for my profession.  There are so many ways to guild lilies these days, and patients will rarely disagree with the recommendation of an “expert.”  Rampant medical inflation is the result.  Whatever the placebo benefit– it’s not worth the cost.

George
Feb 5 2019 at 7:19pm

If anyone heard Gary’s comment that “lower back pain in general is one of the most responsive of troubles to the placebo effect” and wondered how they could make this mind-body connection help them personally, I’d recommend John Sarno’s Healing Back Pain.

Steve House
Feb 6 2019 at 12:57am

Good discussion.  I haven’t read much of the literature about this, but the theory that perhaps the body already naturally has much of what it needs to cure many maladies is fascinating.  My college-age son (electrical engineering) apparently heard quite a bit about this effect in a psych class, including mirror neurons, and we had a fun discussion.  During the interview I was reminded of the movie Split, where the main character has dissociative identity disorder.  In this over-the-top version each of his identities can radically change the morphology and chemistry of his body.  For those of us who might lean toward Christian theology, perhaps the body’s ability to fix itself was lost in the Fall and we are left with remnants and shadows of what once was perfection given by our Creator…?

Ed
Feb 6 2019 at 4:06pm

Does anyone know the link to the milk shake study referenced in this weeks podcast? I would love to see that data. thx

 

Don Crawford
Feb 23 2019 at 2:13pm

Here is a link to the milkshake study

http://psycnet.apa.org/record/2011-09907-001?doi=1

Also note the analysis of it from Dr. Gorski in my comment below.

JonB
Feb 7 2019 at 1:06am

I wouldn’t spend one dime of my own money studying placebo effects…

The subset of the 10,000 unique brain proteins that constitutes the physiological substrate of the placebo effect is likely small and their vector length is small as well. Significant lasting placebo effects in autism, schizophrenia, bipolar disorder, and chronic regional pain probably approach zero. These patients run through an endless series of committed physicians with empathic manner and reasonable theoretical interventions, Their long-term course is dismal. NIDA estimates that 40% of “accidental” overdoses from opioids are actually suicides. Everyone with enough chronic pain breaks eventually as John McCain testified during the 2008 Republican convention, citing his Vietnam torture experience.

Its attractive to think that caring makes a difference. Does it? Is this a story physicians tell themselves to justify their useless therapies in poorly understood disease? All things being equal, of course one would prefer an empathic doctor with a diagnosis of pancreatic cancer or Alzheimers disease but do we need to divert a precious fraction of the 18% of GDP that we spend on medical care on poorly defined theories of “healing” that “probably” would benefit from a fuller understanding of the placebo effect?

Please spend money and intellectual capital on very granular topics whose secrets may take decades to understand, e.g.. TRAP1 mutation in irritable bowel syndrome or NMDA blockade in chronic depression.

This discussion is the clinical equivalent of macroeconomics identities….There is no micro here….

 

Jeffrey Hall
Feb 8 2019 at 9:28pm

I wanted to point out that the studies looking at vertebroplasty and related kyphoplasty actually do support the procedures, as noted in the below review article. http://www.ajnr.org/content/early/2017/11/23/ajnr.A5458

There were a few studies that demonstrated no benefit, but these studies looked at fractures up to a year old, where the mean bone healing time is <8 weeks, and looked at outcomes at 30 days or longer. Subsequent studies have selected for fractures of <8 weeks and demonstrate improved pain at 24 hrs and shorter hospitalization.  In the episode, Russ recounted a story where during a clinic encounter he fortuitously stopped himself from demonstrating his superior knowledge of the field of acute orthopedic pain management to a clinical nurse based on a study he believed demonstrated no measureable difference between those that got treated and those that got sham treatment [assuming the study he was referencing was the NEJM INVEST trial, it actually failed to demonstrated a difference among people with fractures that should have already been healed (baseline fracture age 16 and 20 weeks for treatment and sham treatment arms) who underwent treatment for unhealed acute fracture]. This actually demonstrates a good point: that reading and interpreting the data presented in research papers is difficult, easy to overgeneralize, and that media reporting of such studies (my guess is that the knowledge was based on reporting on, rather than direct reading of, the study, though my assumption may well be errant) is quite often wrong. The study (and others like it) did demonstrate reasonable evidence that old fractures with resultant an atomic distortions likely have no benefit from vertebro- or kyphoplasty. It was not set up or powered to tell whether acute fractures benefited from either procedure, either in terms of long-term outcome or acute pain control.

As Taleb I believe has suggested, heuristic knowledge may be at least as valuable as empirically quantifiable data. While I was initially skeptical of these peocedures, my experience has mirrored the nurse in the story: patients go for kyphoplasty unable to even roll over in bed without intense pain, requiring substantial doses of opioids, and after procedure are out of bed walking the hospital hallways with minimal pain and minimal analgesic need.

Don Crawford
Feb 23 2019 at 11:37am

It is odd to think that some drugs or interventions that get to Stage 3 clinical trials show an effect, but not more of an effect than the placebo.  Both the placebo and the new intervention work equally well.  And yet, even though it “works” for some people, the new intervention is not approved for use.  It does seem like the control we should be comparing to is the condition without either the placebo or the intervention, because that’s what we are left with!  If the placebo and the intervention each cure 19% of the people, but saying there is nothing to be done for you cures only 5% of the people then the no-better-than-the-placebo-intervention is still somewhat efficacious. Maybe it should be on the market as a low-cost, generic dextrose pill with a fancy name?

Comments are closed.


DELVE DEEPER

This week's guest:

This week's focus:

Additional ideas and people mentioned in this podcast episode:

A few more readings and background resources:

A few more EconTalk podcast episodes:


AUDIO HIGHLIGHTS
TimePodcast Episode Highlights
0:33

Intro. [Recording date: December 17, 2018.]

Russ Roberts: My guest is psychotherapist and author Gary Greenberg. He first appeared on EconTalk way in September, 2010, when we talked about his books The Noble Lie and Manufacturing Depression.... Our topic for today comes from a recent article of yours in the New York Times Sunday Magazine that we'll link to entitled "What if the Placebo Effect Isn't a Trick?" Let's start by defining what the placebo effect is.

Gary Greenberg: Well, you are going to start in a really hard spot, because nobody has a really good definition of the placebo effect. Let me give you two that will show you the extent of the problem. One version of the definition of a placebo effect is: Any effect of a medication that isn't due to the medication. Which is simple and straightforward. But there are problems with that definition. And, the other definition is: Anything that happens in a clinical trial that isn't related to the effect of the medicine. Or, to put it another way: Everything that happens in a clinical trial except for the medication effect.

Russ Roberts: And why are those different?

Gary Greenberg: Well, the difference is the placebo effect as we think of it now is almost entirely an artifact of the process of trying to experiment and find out which treatments--mostly medications, but to some extent other medical treatments--work. And which don't. So, to limit it, to define it by means of the clinical trial, which is the method by which the Food and Drug Administration [FDA] requires makers of drugs and devices to prove that they work--to define it in those terms is to give an idea of how the placebo effect really functions in medicine. It's the stalking horse against which all of the other horses have to race in order to show that they deserve to not be put out to pasture. And so, what that tells you is that the placebo effect is really just the flip side of medicine. It's like the evil opposite twin from the medical point of view--the evil opposite twin of the medication--because it also has a healing effect that nobody very well understands or control.

Russ Roberts: And in those clinical trials, the way this manifests itself is that a population will be split in half. One half will get the real medicine, so to speak; and the other will get--typically what? A sugar pill?

Gary Greenberg: Yes. Some formulation that looks and tastes and in every other way is exactly the same as the study drug. The only difference is that it is inert. It would be made of dextrose or something like that.

Russ Roberts: And I know this sounds like a stupid question, but after I read your article I realized it's not really a stupid question at all: The people who--the participants in these clinical trials have no idea which they are getting. They just get a pill.

Gary Greenberg: Generally, that's the case. It's called the double-blind, placebo-controlled method. So, what that means is that neither the experimenter nor the subject knows whether they are getting drug or placebo. And that, in turn, reflects the hope that they've managed to make the two treatments exactly equivalent with the exception of the molecule that's in the active drug.

Russ Roberts: Yeah. It's a strange test when you think about it, because, if it weren't for the so-called placebo effect, you wouldn't have to give anybody the sugar pill. Right? You'd just say, 'You're not on the trial. We're going to see how your health goes over the--you're not getting the medicine.' Or, 'You're getting a sugar pill, and we're just doing that just to kind of have you kind of come in and go through the same kind of stuff that the other people are going through. But, by the way, you've got a sugar pill.' That's not what they do, typically.

Gary Greenberg: No. And the reason is that--well, there are a couple of reasons for that. One is that the idea, the general received wisdom about placebo is that it works somehow or other by deception. That is to say: If you know that you are getting a placebo, somehow that's going to diminish its effect. Or change its effect. And so, telling people that they are getting a placebo theoretically would reduce the placebo effect. Now, interestingly, to the extent that that question has been researched, it doesn't necessarily prove out. So, the ongoing use of the placebo in the clinical trial is really just there to reassure everybody that they are actually seeing the work of the drug and not the work of treatment in general--not simply the work of being exposed to a healer or to the medical industry in any way.

5:57

Russ Roberts: One of the things I took away from your article is that that's something of an illusion: That they are only getting the medicine. And, of course, the part that--I don't think you wrote about this, but it's got to be an issue--it also means the way we conduct clinical trials that the people who get the "real medicine," the people who are getting the molecule that purports or trying to figure out whether it helps or not--those people have some awareness they might have a placebo.

Gary Greenberg: Well, part of the process of being in a clinical trial is being informed that you have a 50% chance of getting a placebo. So, presumably everybody in a clinical trial that's placebo-controlled knows that that's a possibility. They just don't know whether or not they've got the drug.

Russ Roberts: So, if I told half the group, 'Oh, you've got the placebo,' and I told the other half, 'You've got the real drug,' you'd think you'd get--from what I've learned--you'd get a different result than if everybody thought it was a 50-50. Because some of the people getting the real drug are thinking, 'This might not be the real drug.' And that's psychological awareness, perhaps, has a negative impact, just like the people who get the placebo are sometimes getting an improvement in the trial at all just from the possibility that they might have the real drug.

Gary Greenberg: That's right. And so, what you are really getting at there is the fact that every clinical trial has a placebo group--virtually, every one--and therefore is a study of the placebo effect as well as of the drug, there hasn't been a whole lot of inquiry into the placebo effect itself. So, the scenario that you just described--you could actually find that out fairly easily. You would have to have a group that you tell you are giving a placebo, but give them the real drug; and another group that you tell that to but you are honest; and then the same with the drug--a group that gets it thinking they are getting it and a group that gets it thinking they are not getting it. And that would really answer a lot of questions, once you crunched the numbers. The problem with that is, a). Who are you going to get to pay for that? And, b). Even if you get somebody to pay for it, you have to deceive your subjects. And, while that's not impossible, that's a higher bar to cross than most researchers are willing to go in order to get the research approved by the government funders or the university or whoever is providing the funding for the study.

8:26

Russ Roberts: It's a serious ethical question, obviously. And we're going to come back to it, I think, more than once. Especially when I'm talking to the author of a book called The Noble Lie. In which these issues that are raised by the placebo effect reminded me of your book. We all--most of us would say--'Well deception is wrong.' But if I deceive you and improve your health, it's a strange moral conundrum. And, the point I want to make--and, actually, I'll re-quote from the article. You say the following:

Give people a sugar pill, they have shown, and those patients—especially if they have one of the chronic, stress-related conditions that register the strongest placebo effects and if the treatment is delivered by someone in whom they have confidence—will improve. Tell someone a normal milkshake is a diet beverage, and his gut will respond as if the drink were low fat. Take athletes to the top of the Alps, put them on exercise machines and hook them to an oxygen tank, and they will perform better than when they are breathing room air—even if room air is all that's in the tank. Wake a patient from surgery and tell him you've done an arthroscopic repair, and his knee gets better even if all you did was knock him out and put a couple of incisions in his skin. Give a drug a fancy name, and it works better than if you don't.

Now, these are the--just various examples of the placebo effect in action. The willingness of our--of something to happen that is not related to what we think is the therapeutic treatment. So, tell us what we know about how the heck that's possible.

Gary Greenberg: Very little. You know, it's widely observed; it's been widely observed for many years. And, let's remember that prior to, say, 1860 at the earliest, almost all medical treatment was, worked by, well, relied on the placebo effect. Or, another way of saying that is: Most of it didn't work by the mechanism that it was thought to work. And, in general, there was no reason for it to work at all. There are a few exceptions. Aspirin is an ancient remedy. Some of the, you know--Pepto-Bismol has an ingredient in it that has been around for a long time. But, for the most part, we are--if you go back in history, all the treatments were placebo treatments. So, the fact is that, it defies in so many ways the standard model of understanding about healing, about illness, about how to study these things, that it's been very difficult to pin it down. But, let me say one thing about that list, which you prefaced by talking essentially about deception. There are some pretty strong studies that show that if you just tell people that they are getting a placebo, they get better. That has to be in certain conditions. And with certain medical conditions and under certain treatment conditions. But, deception may not be as central to it as we think.

11:34

Russ Roberts: So there are two pieces to your article that I was fascinated by. One is the possibility that the placebo effect is related to the level of empathy or the style in which the placebo is delivered; and the second is a possible genetic difference among people in having a stronger versus a weaker placebo effect--and that genetic difference is not stupidity. It's not somebody saying, 'Oh, I'm going to say a magic word here and your cancer is going to be cured.' It's rather that, literally, some of the placebo effects observed in at least clinical trials vary by genetic markers. So, let's start with the empathy question.

Gary Greenberg: So, there's a theory out there is that what's happening in the healing encounter is that the healer--the physician--is, in order to do his or her work, has to try to understand the patient's situation from the inside. Now, we know that there are many, especially as you get into rarified, specialties that the stereotype is exactly the opposite. That, the subspecialist is more interested in the particular disease or the symptom or the surgery or whatever it is that the person needs than he or she is in the whole person. But, at the level of primary care for sure, medical care involves being empathic with somebody who is suffering. And the idea there is that, when you do that, you set off a series of events that--and this is real preliminary--but that may modulate the body's own healing abilities. So, for instance, there's research we know from other areas in which, we know there's something called mirror neurons. And, mirror neurons are networks of brain cells that respond to watching somebody do something that you're familiar with as if you yourself were doing it. So, somebody having an experience like sadness that you yourself are familiar with, your brain actually looks like the brain of the person who is sad. And that's thought to be related to empathy. I would go so far as to say it's the cause of it. But it may be the signature of it in the brain, loosely speaking. And so there's research that's emerging--it's in the very early stages--which shows that when there's a successful therapeutic alliance between a healer and a patient is that one of the things that's going on is that their mirror neuron networks are being activated. And so that's very suggestive that if there is what they call brain concordance between a healer and a patient, that that may help the healing process. Which isn't to say that whatever the treatment is isn't also part of it. But that in a way the treatment is the occasion for this expression of empathy or care or concern or whatever you want to call it. And that that isn't just window dressing, and that isn't just their making you feel good for a moment. It's somehow related to the fact of healing. You know, we can look at, I don't know, an antibiotic eat a bacteria in a test-tube; and that will tell us that antibiotics eat, you know, eat bacteria. But nobody with an infectious disease can say exactly why that treatment is what makes you feel better. Or get better. We're pretty close to being able to state it as a fact, but if you think about it, there's still a little bit of a gap even in that most objective kind of medicine, of, say, giving somebody penicillin for an infection. There's still a little bit of a gap there that we just don't fully understand. And it's possible that that placebo effect is part of what's in that gap.

Russ Roberts: We had David Meltzer on here a few months back, and he's looking at--he's looking at a few things, but one thing he's looking at I would think of as empathy or more wholistic approach--this is my memory of the moment that you are reminding me of, where doctors interact more conversationally with patients rather than making sure they fill out all the right checkboxes and medical record data. Instead, they chat with the patients. They give them a lot more one-on-one time. And that also originated, by the way, as a story in the New York Times Sunday Magazine. In that article the author talked about Meltzer's physicians in these trials that they're doing learned things about the patient that they might not otherwise have known. They find out they were playing poker last night, ate a lot of French fries, and therefore maybe that's why their cholesterol spiked. That kind of fuller picture, or anxieties from their daily life, you wouldn't otherwise know about that might explain some of their conditions. But, hearing you talk, it makes me think maybe a lot of what they're doing is just a placebo effect. It's the emotional--and Meltzer may have talked about this, so I'll have to go back to the episode--but a lot of it may just be the emotional comfort, the body being in a healthier situation, that someone's listening to them and seems to care at least, or maybe actually does care, even better. So, that's the first thing I want to mention. The second thing I want to mention is Lynne Kiesling, economist, has looked at mirror neurons and the correspondence to Adam Smith's work in The Theory of Moral Sentiments; and as listeners know, I'm a big fan of that book. We'll link to that article as well--this question of what's exactly going on. And the fact that you raised this issue--when people are perhaps responding to a doctor's care--but this idea that we don't even understand fully--you say we're close. I wonder how close we really are in understanding the power of antibiotics or chemotherapy. It would seem, as an amateur, novice, layperson with no real knowledge, I always thought, 'Well, we know how these pathways work.' So, if we don't--if some of it is the unleashing of the body's own anti-immune system, I mean immune system; and also the body's ability to fight various infections automatically, which probably is just the English phrase for immune system. It's crazy. It's crazy to think that through emotion and the feeling that you are being taken care of or the idea that something you are putting in your body is going to help you--just the idea of it--could focus those inner strengths and stratagems that your body already has.

Gary Greenberg: Yeah. I would say that--'crazy' is an interesting word. To me--

Russ Roberts: Wrong word. For talking to a psychotherapist, maybe.

Gary Greenberg: Yeah. Maybe so. Unless you want a diagnosis. Um, it is a little crazy-making though. If you--if the definition of illness and healing is limited to the actions of molecules upon molecules--you know, an antibiotic on a bacterium--then it is a little crazy-making, because it makes it hard to talk about all this other stuff. So, even the little--even the things that you were saying just a minute ago, a doctor would hear that, could hear that and begin to really worry that you are about to tell people that, you know, vaccines don't really work. I know you're not. But, you know--there's such a strong set of beliefs that the way medicine works is objective: It works despite who you are.

Russ Roberts: It's science.

Gary Greenberg: It's science. Yeah. And science has been construed as this way of knowing that provides certainty. And doesn't, you know, sort of rules out the random. It rules out the subjective. And, I'm not--I think that there's some truth to that. But I also think that, when it comes to medical treatment, we underestimate the extent to which our experience, our expectations, our understandings about healing and illness are indebted to historical accidents. For instance, the first advances that really start modern medicine were advances that recognize germs as the cause of disease. The discovery of anthrax, of smallpox, of cholera--all of those 19th century--syphilis. Nineteenth century discoveries of these bugs that were creating illness.

Russ Roberts: They are real bugs.

Gary Greenberg: They are real bugs. They really exist. And really when you do something to not exist, or not so much, you end up feeling better. Or being better. Or surviving. You know. And this is--you know, I don't want to underestimate this at all. This is revolutionary. The fact that--it changed everything. I mean, look at the fact, what it means to know as a parent, today, that if your kid gets strep throat, 99.9% of the time you can give him some drugs and he's going to be just fine. A hundred and fifty years ago, that kid probably could have died. And that would be a real possibility. Or get scarlet fever and end up maimed for life. That was a real possibility. So, I don't want to underestimate this. But, because those were the early discoveries, this is our idea of medicine. It's a magic bullet model. You find the cause in the body and you aim your bullets at it and you kill it. And, while that works for some things, it doesn't work for others. And, more to the point, we may be, I don't know, mistaking the basic mechanism. We may not really understand the basic mechanism. You don't really have to. You know? If it works, it works. But, when you then go to branch out to other, more mysterious, more complicated illnesses, you find that it doesn't work quite so well; and in fact it's possible the low-hanging fruit has been picked. And that with the proliferation of immunological diseases, autoimmune diseases, or complex cancers, and so on, we may be looking at the kinds of illnesses that simply aren't going to respond to that model. And among those conditions, I think are some conditions that do respond strongly to placebo treatments: chronic fatigue syndrome, chronic pain, irritable bowel syndrome. And there's others. All are illnesses that modern medicine does a relatively poor job with. And that placebo seems to be--well, more effective than you would expect it to be.

23:18

Russ Roberts: So, I mean, pain, we know, is a peculiar thing because we know people can have pain from phantom limbs. So, obviously pain is weird. Pain is somewhat in your head. Of course, everything is in your head. So, it's a little bit tricky. But, you know, somebody who has chronic pain--you'd like to say, 'Well, so here's a painkiller; but actually don't take that because actually they may be addictive. So, instead I'm going to give you a sugar pill. Just think of it as a painkiller.' And that is not good medical practice, in general. Or, to tell people to "think positively," or whatever else. But there's a sense in which this research is heading in this direction, in some degree. Right?

Gary Greenberg: Yes. And what you just got at is--it's a double-edged sword. On the one hand, there's great evidence that techniques related to mindfulness can be very helpful with chronic illness, particularly with the pain component of it. At the same time, you know, you can end up with--you can end up blaming the victim: where the patient feels pain and he or she has been told that that's, his mindfulness could control it, and it doesn't. Like he's failed. And that, you know, that's also a function of what we expect medicine to do in the first place. It's all supposed to happen without us. You know, you could be asleep and we give you the drugs and you are better. So, to introduce human agency--we don't really know how to do that yet; and we certainly have to be aware of the fact that in doing it, you could introduce things like victim-blaming and unnecessary guilt and all sorts of things that could go wrong with that formulation.

Russ Roberts: And unnecessary doubts, for people who think they can avoid some challenge, health challenge by just thinking their way through it or meditating over it. I mean, if you read the Walter Isaacson biography of Steve Jobs, there are some strange things he did to himself when he was suffering from cancer that I feel--I worry, I feel sadly--that, you know, he was rejecting some--he was accepting some alternative treatments that probably didn't help him. So, as you said earlier, I want to make it clear: Nothing we're saying here is anti-science or anti- the many--it appears to be the many wonderful successes of what we might call Western medicine: the purely objective, scientific method for intervening in the body. But, there are just some mysteries here that we don't fully understand. And I have to tell a story--I've told it before, but it's so appropriate. I heard it told about Niels Bohr, I think. It's not really, I think, about Niels Bohr; I think it's been told about many people, Einstein and others. The student goes into Bohr's office, and, as he's leaving after chatting about some homework problem notices a horseshoe over the door. And the student says, 'Oh, well, Professor Bohr, you don't believe in that, do you?' And Niels Bohr answers, 'Well, of course not. But they say it works even if you don't believe in it.' It's the same kind of crazy, unscientific, unobjective, impossible result--that something magical is happening.

Gary Greenberg: Yeah. And actually, that's--that happens in real medicine, too, right? Because, why--you look at a pill. A pill is tiny. Right? It's just this little thing. And it has no taste. And you swallow it, and all of a sudden, something--or maybe not so suddenly, but eventually, something really quasi-miraculous happens. I mean, where's the--there's magic in that, too.

Russ Roberts: It's true.

27:10

Russ Roberts: So, I'm going to tell a story. I don't think I've told this before. But, I'll let you react to it because it's perfect for your article and this conversation. I had some shoulder pain. So, I went in to get a steroid shot. And one of the things that--I had a tear in my rotator cuff, despite my lack of baseball experience. And I--this happened 5, 4 years ago maybe: I'm 60 years old; I'm laying on the table; and it's a really cool thing. They've got a--of course, I'm not paying for it, so it's not perhaps as cool as it should--I should probably feel some pain about this, but I don't. I'm enjoying watching the fact that the doctor gets to put the needle exactly where she wants to put it. Because she's watching my shoulder on some kind of scanner. And I can see it, too. Which, of course, is a perfect placebo effect: I can actually see, 'Oh, the needle is going right where it's supposed to go.' And of course, my shoulder got better, either because of the steroids or the placebo effect. But while I was waiting for the doctor, I was chatting with the nurse; and I said, 'What's the coolest thing you've seen in this office?' And she said, 'Oh, it's this amazing thing. These people come in with back pain, and we put this cement in their joints. And it--it's magical. Their pain just totally disappears.' And I said, 'Well, that's very cool.' Which was restrained on my part, because a week or few, maybe a month before, I had at some point recently interviewed Adam Cifu, EconTalk guest, about his book, Reversing--I may get the title wrong but we'll put a link to it [Ending Medical Reversal--Econlib Ed.]. And basically what they find when they actually do clinical trials of this technique, which is called vernoproblastia [vertebroplasty?--Econlib Ed.]--I don't know how to pronounce it, but where they put cement into your vertebrae to get rid of back pain from osteoporosis--there is no difference between doing the treatment, where you actually go into this person's back and inject cement, versus laying him down, opening this cement so they can smell it, and then injecting saline into their vertebrae. And, of course, in a certain dimension--so, what did we learn from that? So, I kept my mouth shut. I didn't say, 'Did you know that doesn't work?' And now that I've read your article--the doctors in that office are particularly empathetic. They are wonderful people. They are great listeners. Maybe that's why their vertebroplasty does have a big placebo effect. But, what do you learn from that? You can't say to people, 'Well, you've got back pain, so what we're going to do,' you really don't want to inject the cement, 'we're just going to let you sniff this glue; and we'll inject some saline.' That's not a viable alternative. So, in what dimension is this placebo effect a horse that has to be beaten, a real horse? It's not even a real horse. It's strange.

Gary Greenberg: Well, yeah. It's because--you say with some certainty, and I'm not disagreeing with you, that you can't just tell people, 'This is what we're going to do.' But, in part, that's because we're pretty well socialized to expect a certain kind of treatment; and the kind of treatment we are led to expect is not, you know, of saline injection accompanied by a lot of really nice people. However, medical treatment, no matter what it is, is a ritual. And so, what we could learn from that is what we learn from all of these studies. And, by the way, that lower back study that you mentioned is one of a number of studies that show that lower back pain in general is one of the most responsive of troubles to the placebo effect--to placebo treatments. So, what we learn is that, in addition to that there's more things under heaven and earth than you've dreamt of, is that the ritual is very, very important to the outcome. That, especially in a certain group of people, and this gets back to your second point about genetics, especially in a certain group of people with a certain group of illnesses, the ritual part of the treatment becomes very important.

Russ Roberts: That book is called Ending Medical Reversal, by Adam Cifu, and it's co-authored with Vinayak K. Prasad. So, the ritual is important. And that's challenging to our view of that science.

Gary Greenberg: Well, you know, the very word 'ritual'--it's like myth. It gets people's--if you are a scientist or a physician, married to the scientific method, you start to feel like somebody's trying to say something bad about you, if they say it's a ritual. I actually don't think so. I mean, I'm a psychotherapist: I believe what I do is I practice--

Russ Roberts: A lot of ritual--

Gary Greenberg: Well, yeah. I believe I deliver a placebo treatment. I think I do a really good job of it. For the most part. But, I couldn't tell you what the active ingredient is in psychotherapy. And I think that to some extent, that goes on in all medical treatment. So, we have our rituals. And, by the way, one of the interesting things that's happening in placebo research is that there is a mystery as to why the placebo effect is getting stronger as time goes on, at least with respect to clinical trials. In other words, as time goes on, each clinical trial is more likely to show a stronger placebo effect than they used to. And this has become a problem, because if the drug can't beat the placebo, the drug can't get approved. And so many companies get their drugs as far as the Phase 3 Trials, which is where the rubber meets the road; and they find out that it doesn't really beat the placebo, and it's withdrawn from the market, as if that means it doesn't work. But, what it may also mean is that people have come to--that the placebo effect has been augmented, maybe by advertising or by expectation. Yeah. And, it may be that the clinical trial setting--if you've ever been in a clinical trial, which I have, you get treated like royalty. They are never late. And if they are, you know, 5 minutes late, they apologize. They love you. You are worth money to them. And they treat you really, really well. You get the undivided attention of many physicians and nurses. For many weeks. And it could be that that is one of the reasons it's increasing, not because the treatment itself is increased but because while that's been going on, the rest of our lives in the medical industry have been getting worse. The doctors are more harried, the treatment is more fragmented, etc.

Russ Roberts: It's also, I think, people increasingly, whether it's legitimate or not, think that doctors are saving the world and that everything works; and we've had a guest on here and I've talked to my own friends who are doctors--every patient assumes, and every family member assumes there's a cure for everything. You go in and the doctor starts describing why the patient is in very bad shape and people need to start getting their relationships in order and their affairs in order; and the family member says, 'So, what do we do next?' And the answer is, 'There's nothing to do. It's time to say goodbye.' Which we as human beings find infinitely painful. But we find it now intellectually perplexing, because of course we've figured out "everything"--almost everything. Surely there's another treatment to try, another drug to take in. And I think what you're saying is that would enhance the placebo effect. Bizarre.

Gary Greenberg: Yes. That level, that set of expectations I'm sure is related. And, you know, the rituals there are immensely important. Think about the patients that spend their last two weeks in the intensive care unit. Now, you know, a lot of times that is primarily treating--I mean, obviously, they are doing things. But who are they really treating? Are they treating the patient or are they treating the family, when nobody will say that it's a lost cause? So, it's only tangentially related to the placebo effect, but it shows you the extent to which we grant authority to these rituals.

36:24

Russ Roberts: Yeah. I'm thinking about pediatrics for a minute. I'll tell you why: I remember when we had our first kids, we were getting advice on doctors, and people recommended a particular doctor, and they'd say, 'Well, he's not very warm and he's not good socially, but he really knows his stuff.' And, in my mind, that's the kind of doctor I want. 'I want the doctor who knows his stuff. I want the doctor who has got the best training, who has seen the most cases, has the best hard drive--mental hard drive, this is slightly pre-internet, 'Right? I want them to be able to pull on all that knowledge. That empathy thing? It's just gravy. It's just--I don't need that. I'm not even willing to pay for that.' And I suspect--I suspect--we've been talking a little bit about how doctors find this alarming or puzzling or troubling--I suspect there are a lot of doctors out there, and maybe some of them are listening and I'd like to hear from them, who believe in this overwhelmingly. Who very much believe that their bedside manner and their level of empathy makes a difference. And some of that's self-deception, of course, and confirmation bias. But I think a lot of doctors believe that. And of course they're the ones who have the best bedside manner. The ones who don't, probably think it doesn't matter much at all. But, I'm thinking them about pediatrics where, I wonder--that would be an interesting place to look. Right? For this effect. Because, kids are going to, infants are going to respond at an incredibly visceral level--I'm not sure what the word 'visceral' means in that sentence, but, a primitive, non-rational level to emotional care. And we know infants respond to that. So it would be interesting to see if, free of all the baggage or knowledge we would still respond to some kind of placebo.

Gary Greenberg: Yeah. Right. These are all interesting ideas about how to study it. Of course, that's not getting done because there's no money in it.

Russ Roberts: There might be.

38:30

Russ Roberts: Let's talk about the genetic thing. We didn't get to that. What's the genetic recent findings, that suggestion, that have something to do with this?

Gary Greenberg: Well, there are findings that show, there are some studies, as I mentioned before, that have been done with open-label placebo--in other words, you tell people they are getting a placebo. And you compare their response to people for whom you literally do nothing. And you also compare the responses of people told they are given placebo to people who are told with a great amount of detail and attention and warmth. And what you find is what you might expect: the no-treatment people do worse; the placebo-receiving people--people receiving placebo with some explanation--do better; and the people that receive a lot of attention and care along with their placebo and explanation do the best. It's small studies; they are with irritable bowel syndrome. But if you then take the people who do the best on the placebo and you look at their DNA [deoxyribonucleic acid], what you find is that they vary in a predictable way. People who have one particular variant of a snippet of the genome are more likely to have a strong placebo effect than people who have the different variant of that same snippet of the genome. And so, what you find--and this finding has been, not exactly replicated but at least supported by large-scale studies that show--you know, one study that has 40,000 participants followed for 10 years--showing that the same set, the same area of the genome which produces a particular enzyme is related to the response to placebo. And this isn't for irritable bowel syndrome. This is the response to placebo for the prevention of heart disease and also, I think--this study will be emerging soon--for the prevention of cancer. That, there is a relationship between taking a placebo and avoiding those diseases--the placebo, people were taking placebo Vitamin E or aspirin. And there's a relationship between taking the placebo and not getting those or being prevented, having prevention from those diseases. And, the indication is that when you have a certain kind of genetic makeup, you are more able to make use of the placebo effect. Or, conversely, if you have a different genetic makeup, you not only can't use it, but in some ways it looks like it might affect you negatively, to be taking a placebo. Which is a very strange idea. In the absence of side-effects--you know, a placebo that somehow creates side-effects--it's very odd to think that the placebo could actually make things worse. And, the explanation for this is that all of these effects are modulated on the same neural pathways, which is a neural pathway that has to do with dopamine. And that, what the body--what we're really looking at is the body's ability to detect disruptions to homeostasis, and then to restore homeostasis. Not just in psychological disorder, but in physical disorder. So, there's this long chain of reasoning that is increasingly getting empirical support indicating that the reason that there's a placebo effect is because we've been misunderstanding healing all along--that there is this neural aspect to healing which is about more than just, you know, antibiotics eating bacteria or cancer chemotherapy agents eating cancer cells. That, it actually has to do with some healing process that is modulated by the central nervous system. And these findings are very suggestive. They are very early stages. But, when you really look into it, it doesn't seem all that implausible. And, one of the effects of this is that it indicates that the whole model of the clinical trial might be wrong, because it assumes that the placebo effect is part of the drug effect. Or that--sorry--that the overall effect is the outcome of the placebo effect plus the drug effect. It doesn't take into the consideration the possibility that they might interfere with each other. It doesn't take into account the possibility that a placebo might actually stop a drug from working. Or might make a person worse off to start with. Or vice versa. And this is a real challenge to the clinical trial model. But, it's really basic. Nobody has stopped to ask, 'Wait a minute. Are they really additive? Is the placebo effect plus the drug effect really the healing effect?' Nobody ever proved that. They just assumed it.

Russ Roberts: And I like to think of the body as a complex system--

Gary Greenberg: Yeah. Yeah, I guess that's an interesting--

Russ Roberts: well, [?]--well, for me, it brings a lot of baggage with it. It means I see it as an emergent system; it's something like the economy; it's prone to unintended consequences. The policy interventions are not always as straightforward as we think. We have to ask the question, 'And then what?' And actually what you are saying, in so many words, you are saying that, 'We don't fully understand the underlying complexity; and if we don't, we don't understand then what we are actually doing when we intervene in these particular ways.'

44:21

Russ Roberts: I want to take us down a path that you only allude to in the article, which is weight loss. We had Gary Taubes on here, a long time ago, a couple of times. And many listeners have told me they've lost tens of pounds--30, 40 pounds. It changed their life. And, I remember telling this to a friend of mine, and he said, 'Oh, no. That's all nonsense. The China Study shows that what we really need to be doing is x, y, z.' I've looked at the China Study; it doesn't seem to be a very reliable study. But my friend lost an immense amount of weight following a very different paradigm than the Taubes more Paleo approach, of low-carb and not worrying about fat. And, I've said this on the program--I've said it in humor, but it's always crossed my mind that if you believe in the diet you are going to lose weight even if there is no "science" behind it. And that's a joke, I've always thought. But maybe it's not such a joke. In which case, listeners who lost 30 and 40 pounds, probably shouldn't be listening to this next part. Because, I don't want to spoil it. But, I mean, that's where this kind of starts to get crazy--I'm going to say 'crazy' again. Weird, Ouroboros-y. I don't know. Circular. Non-stable.

Gary Greenberg: Yeah. I think that's right. I think the connection there is that--I mean, aside from the fact that maybe the weight loss is not a simple matter of metabolism. Right?--

Russ Roberts: okay--

Gary Greenberg: of what you eat and what you don't eat and so on, and how much you exercise. But that it also has to do with how you are, what your mind is doing. And there is--as you read that paragraph from the article, there is good research at Stanford that shows that the gut response--I mean, our gut is fully--people are now talking about the gut-brain, right? That there's so much neural activity in the gut. So, it's possible that the placebo effect could be related to weight loss. I just don't--aside from the studies showing the secretion of peptides is related to the expectation of the person who is taking them--which is a pretty astounding finding, really--you take, you know, if you give somebody a milkshake and you tell them it's diet that their gut behaves one way; and you tell them it's just a regular old milkshake, their gut responds another way--that shouldn't happen. But it does.

Russ Roberts: It also raises the question of how you clinically test dieting. Right? Because, it may matter a lot about what you tell people, and what you do to their expectations. I used to have this--I don't remember who first told me the joke, but, you know, somebody offers me a brownie, and I say, 'I'm trying to lose some weight,' and they say, 'Oh, don't worry. All the calories are in the last one.' And if I could just believe that, maybe it would be true. I mean, this is just--it's a terrifying--I don't believe that, by the way. I don't think that that would work. But you're suggesting there is something to that.

Gary Greenberg: Well, there might be. Yeah. If this research proves out, maybe you just order yourself 16 brownies and only eat 15 and you'll be fine.

Russ Roberts: Heh, heh, heh.

47:38

Russ Roberts: I think, to get serious again--not that that's not serious--

Gary Greenberg: Oh, come on.

Russ Roberts: There's some seriousness there about the psychological expectations part. But, you know, when you said there's no money in it: It would seem to me to be there's an immense amount of money in this, in fully understanding. It's not money you might be able to capture. But, you would think that foundations, and possibly the NIH [National Institutes of Health], would be deeply interested in getting a fuller understanding of the pathways of healing that we don't fully understand.

Gary Greenberg: Well, here's the sad part of that story. Everybody knows that--well, first of all, the reason I said so glibly there's no money in it, is because, in the end, the money to bring something to market--whatever that might be--is generally provided by private industry. But as I'm sure you know, they are essentially helping themselves to taxpayer-funded research all the time. So, what I really meant by 'there's no money,' is that the drug companies can't figure how to make money off of it. But, I agree with you. But, the sad part of the story is that, um, the NIH has had a Center for Complementary and Alternative medicine, for many years now. And it's run by good people. The fellow who I think was its first director, is no longer, he's retired. But, and some of the people I interviewed for the Magazine article are active and get a lot of their money from that Center. But, so far, anyway, they have been unable to come up with very strong results about anything. Whether it's complementary medicine like homeopathy or chiropractic or studying the placebo effect. Or, what happens is: The more you increase the population of your study--or, let's say you do a lot of studies and then somebody does what's called the meta-analysis, to do a study of studies--the placebo effect begins to recede. Because this contradicts everything we've been saying to the last 45 minutes, or whatever. Because it begins to look like well, maybe the thing doesn't exist after all. But, what has happened is that, we have not been able to detect a strong-enough signal to know in what direction to move, in order to exploit the placebo effect in the standard way that we exploit other medical knowledge. I think--this is part of what I was trying to write about in this article--that that may be because the placebo effect has never been something that we could study very well with the instruments of medical science. Bearing in mind, that the placebo effect was really first identified in an attempt to discover whether or not the claims of a, a guy named Mesmer, famous for being Mesmerist, of the whole hypnotic thing--

Russ Roberts: It's mesmerizing--

Gary Greenberg: It's mesmerizing.

Russ Roberts: That's where the word comes from, I assume.

Gary Greenberg: Yes. That's exactly right. And he's practicing this kind of weird, séance-like treatment in Paris in the late 18th century. Which was very effective. It was having very powerful effects on people with fatigue and malaise and odd paralyses and stuff like this. But, the King decided to investigate this, and appointed a panel of leading scientists, including Benjamin Franklin. And determined that the placebo[?]--I'm sorry--that the hyp[?] mesmerism wasn't really doing anything. That it was all in the imagination. And that, in fact, the only thing worth looking at were the things that happened when the imagination wasn't engaged--what they were calling imagination. And that's actually the birth of the placebo effect. That's when placebo was separated off from the rest of medicine. And it was in the century later--the subsequent, the 19th century and then the 20th century, that we became accustomed to looking at medicine the way we do, and developing the instruments and the techniques and the methods for answering questions about health and illness. And so, there's a mismatch that's built in from the beginning from how we investigate illness and healing on the one hand, and placebo effects on the other. And it could be that what's going on is that looking for the placebo effect for those instruments is like looking for feathers with a magnet. It's like, just because you magnet doesn't find the feathers doesn't mean the feathers aren't there. It just means that you haven't quite figured out how to find them yet. So, yes. There's probably money in it. But, that money would have to be, at least at first, based on a new paradigm for even understanding healing in the first place.

Russ Roberts: It seems we ought to think about it. You know, I'm not a doctor. And I'm not a medical philosopher. But, it seems like there is something there.

52:31

Russ Roberts: I am curious what your thoughts are as a psychotherapist, and did this research and writing that article affect your practice in ways you are comfortable talking about?

Gary Greenberg: Well, it didn't. I don't know if it affected it except insofar as it strengthened my conviction that--so, I'm in my office right now, as a matter of fact. In 20 minutes I'll start my clinical day. And people will come in, and they'll tell me their troubles; and I'll talk to them, and I'll listen to them. You know, I hope I can help them understand themselves a little bit better, and whatever--have a better life. But, I think that there's--and so that's what's going on at the manifest level. But I think that, underneath that, there's something else going on that I don't really have a lot of control over, I don't have a lot of knowledge of. But it's somehow transmitting care, on a kind of a, like a secret radio frequency, you know, that is being transmitted to them and they are receiving it. And it's not that it's the words or the thoughts are irrelevant. It's just that they are only part of what's going on. And I just think that maybe psychotherapy is the paradigm case of this. Now, could we find that, that beam of whatever it is--care, empathy, whatever you want to call it--and isolate it, and figure out how it works, and all the stuff? Maybe. But maybe not. I mean, maybe what we got is a situation is where we have a way of knowing the world that doesn't allow us to investigate, um, certain things. And maybe certain things are literally beyond our ken. And maybe this is one of them. I mean, there's a lot of maybes. So, it's changed it in the sense that I'm much more convinced that I am correct about that impression that I've had for many years, that there's stuff going on here that I don't fully understand. And that dates back to the origins of therapy, and the, even the Freudian idea of the transference--the idea that there is, the relationship is somehow primary to the, whatever the healing effect is. So, it--it's kind of strengthened that conviction. But it hasn't given me a better sense of what exactly that is, or how to find it, or how to manipulate it. It's just: There it is.

Russ Roberts: It reminds me a little bit of the Heisenberg Uncertainty Principle--that when you try to get too close--certain measurements aren't possible because the measurement itself affects the outcome. I'm thinking about--maybe you'll know the source better than I do--the old therapeutic phrase, 'Every day in every way I'm getting better and better.' Which, I have to say, I've thought of as a foolish thing. But maybe it's not so foolish. Maybe we can get the placebo effect to work on ourselves through our attitudes, and through our brain. In fact, it makes me wonder whether confirmation bias and overconfidence is just a fancy way to maintain better brain health and overall health.

Gary Greenberg: Well, that could be. And, you know, you start to talk about confidence, and then you are really wandering into the weeds. Because, that is, you know, that is--confidence is probably one of the most poorly understood and one of the most important aspects of our daily lives. And, we see that confidence has very strange effects. Especially, you know, we think about the 'confidence man,' and the idea that somehow confidence is related to fraud. And you think about some of the things that some people say about our current President, as a confidence man. And you see that this ability to believe is crucial. The credulity is crucial. And it's not necessarily a bad thing. But, it's definitely a thing.

Russ Roberts: Yeah. *heh, heh, heh[?]* That's very well said. It's--it can be a bad thing. You can be credulous, I think, about avoiding certain medical treatments that you desperately need, that aren't good for you, again to bring this back full circle. On the other hand, it may be it's good to be credulous about other things that aren't really scientifically known but maybe help you. My first thought, when you are talking about getting rid of your practice: I think it would be good a idea to hack your Yelp account, and whatever your ratings are, Dr. Greenberg, get you a lot of 5 stars, so that your patients, when they think, 'I wonder if this is going to work--oh, well--look how successful. Everyone else is healed by this man. That's all you need.'

Gary Greenberg: That's a brilliant strategy. If I have a Yelp thing. I don't know if I do this. I've actually never looked. But, yeah, sure. That's dishonesty in the service of making people better, right?

Russ Roberts: Well, you know, did you think about your book, The Noble Lie? Because a lot of this has--and I recommend that book. That book really had a powerful effect on me in thinking about a bunch of things. In that episode.

Gary Greenberg: In a funny way, all my books have been about the placebo effect. Either directly, like my book about depression, one of the central parts of it is that, you know, that the placebo effect and antidepressants has largely been created by the advertising. That placebo effects are about marketing. At least in that realm.

Russ Roberts: Yeah.

Gary Greenberg: And, in the earlier book, The Noble Lie, which I barely remember, but I do know that I wrote about, I wrote about my experience a clinical trial, there, and it was a placebo-controlled trial. And then a more recent book, which was called The Book of Woe, is about the making of the DSM [Diagnostic and Statistical Manual of Mental Disorders], which is the psychiatric diagnostic manual, which was a chaotic and vastly entertaining mess that the American Psychiatric Association went through back in the 2011, 2012. And I just sort embedded myself with them and watched it unfold. And you could see that so much of what they were doing with the DSM, by creating this big book of mental illnesses, was creating confidence in themselves. You know--they had these labels, and they could use them. And they could identify people. And that's all about enhancing power. And [?] many psychiatrists--well, I should say, more than one psychiatrist, say to me, 'Well,' basically, 'Well, don't yank the curtain back too hard here, because you'll undermine people's confidence. And people's confidence is crucial to their getting better.'

Russ Roberts: Yeah, that's a tough one. That's a real tough one. A critique of the, you know, the modern, psychological, psychiatric, psychotherapeutic movement is they've made many things that were just part of life--like being sad after someone passed away--a syndrome--

Gary Greenberg: right--

Russ Roberts: to be avoided. Like, disease should be avoided. So, if you get sick, you take medicine; you get better. Whereas I would argue that there are many things in life--tragedy and mourning being one of them--where the experience should not be altered by a medical intervention, except in the case where there's danger to the person, that the part of life is experiencing and enduring those challenges. And we're right at that--talking about the DSM and your book, The Book of Woe, that's really where the, uh, how you draw that line is really important.

Gary Greenberg: Yeah. For sure. Of course, that's a discussion for another day.

Russ Roberts: Well, I wish you well with your practice. In the next 10 minutes--

Gary Greenberg: Thank you--

Russ Roberts: My guest today has been Gary Greenberg....


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