Instant Genius - Placebo: Why this miraculous experience really works

Episode Date: February 19, 2024

The placebo effect is a seemingly wonderful experience, healing people with no apparent cure - but how does it really work? We spoke to Jeremy Howick, an epidemiologist and author of the new book The Power of Placebos to find out. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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the BBC Science Focus magazine. The term placebo gets thrown around a lot, whether that's thanks to its role in studies, or simply its almost miraculous ability to fix health problems without any intervention. But what is causing the placebo effect, and is it something that we can utilize? We spoke to Jeremy Howick to find out more. He's a philosopher and medical researcher, as well as the author of the new book, The Power of Placibos. So it's a term that we throw around a lot,

a phrase that we use quite regularly. But when we're talking about the placebo effect, what is it that we're actually talking about? And I guess how common is it as an occurrence? The placebo effect, not the placebo treatment, the placebo effect is part of the effect. of almost every medical treatment. So it's actually very common. Another question is how powerful is it? How big is the effect? That's a different question. But if you just don't require that it

be a large effect, it's part of any, whatever gets a painkiller from the doctor, antidepressants, post-operative morphine. Most treatments people get surgery. The placebo effect is part of the effect of the overall treatment. So it's almost ubiquitous. And how long is it that we've known about it. Is this something that we've known about for a short period of time, or is this going back centuries now? The use of the word predates its use in medical context. It was from the Vespers sung after people died in the Middle Ages. They used to sing placebo domine in Regioni di Vorum. May the Lord be pleased in the land of the living. And people came from far and wide after these funerals to celebrate and sing placebo. The placebo, they used to call the placebo psalm.

And some people, of course, only had tenuous connections to the person who's dead. They came for the free meal afterwards, and they were insincere. So they'd insincerely sing placebo. And Chaucer called them, you know, flatterers and devil's chaplains singing placebo without having any connection to the person who had sadly passed away. So that's what the root comes from is, I shall please. And the root, in terms of people singing it deceptively back then, also comes now people's belief. It's a false belief.

Now the belief that placebos require deception. to have their effects. Yeah, that was something I was going to ask, is that when we're looking inside the brain, what is it that's actually happening when we experience it? Because I often equate it with this idea of being false and you're being tricked into having that feeling,

but is it not always that? No, when people respond to a placebo. So first of all, placebos are offered deceptively in the context of randomized trials, but it's ethical because you might enroll in a trial of a new drug compared to a placebo. And they'll tell you, you might get the drug

or you might get the placebo, you don't know which is which. So you think that it might be a real drug, which is partly deceptive, at least. And then there are some early anecdotes. So I'll tell you one where a colleague of mine was a junior doctor in a London hospital 35 years ago. And there was a patient of hers who was demanding morphine for pain, but they didn't meet the criteria for morphine because you shouldn't give morphine to someone who doesn't meet the criteria for it. And I was insisting on it becoming very unpleasant my junior doctor colleague went to see her more senior colleague who said ah i know just the thing to do the woman asked about our symptoms and he said i have just the treatment for you it's a special new

experimental treatment went back and came back with in pincers a large tablet and a glass of water dumped the tablet into the water it fizzed up dissolved he said drink this very slowly she felt much better but my junior doctor colleague knew it just there's effervescent vitamin c this is an example of deceptive placebos outside the context of clinical trials. But now we know you don't need to deceive people for placebos to have their effects. A real example, a woman Linda Buonono, she had such bad irritable bowel syndrome or IBS. She couldn't leave the house for weeks. She enrolled in a trial run by some fantastic Harvard researchers, including my colleague Ted Kaptcha, of what's called honest placos, where they told her, here's a placebo pill, which is like a sugar pill, has no

active ingredients in it, but might work due to mind-body self-healing mechanisms. Now, it worked so well for her. She was able to resume a normal life for the first time in years. At the end of the trial, though they took the placebos away, the normal placebos, and took them where they ran out. She went to the pharmacist to ask for some placebo. They said, no, I can't give you these. They're unethical.

And there's dozens of trials. I've reviewed these honest placebos can work. And the reason is, it does would be a cognitive mechanism. Sometimes your subconscious believes it might work despite what your conscious mind says, and by definition you're not in control of your subconscious thoughts. So if you go to see a trusted doctor who tells you this might work, doesn't lie to you'll say will, does it might work? And you've had positive previous experiences of going to the hospital and getting better

or taking a pill and getting better. These previous experience, what you've learned, but your brain, what your body's learned about taking medication and engaging with the healthcare profession can leap to a positive response in the same way that it is deceptive placebo can lead to a positive response. So if we were to utilize placebo and take it into the real world, I mean, right at the start, you mentioned about there's a big difference between placebo effect and placebo is a tool. And if we were to take it into this real world, I assume we'd have to focus on these, I guess, more ethical versions of placebo for it to be accepted and to be given out to people. Absolutely.

So there's two things to separate. One is placebo's. One has placebo effects. I'll talk about the more controversial one of two, when can placebo pills, for example, because you can also have placebo surgery, when can placebo pills or placebo surgery be ethical? The answer is, they've got to be honest, first of all. If you're talking about honest placebo, there's no ethical objection anymore. There's no, because you're not deceiving people. And here's an example, there's an ongoing trial right now, as we were speaking, where post-operative patients are offered a combination of real morphine and placebo. They're told, hey, instead of giving you just morphine pills after you're off. to treat your pain. We're going to give a mix of real morphine and placebo pills. The good thing about

this is that it has almost the same pain-killing effect, almost indistinguishable, but the chances of becoming dependent on morphine are greatly reduced. So that's an example. But then if you move to placebo effects, which is part of all treatments, so if someone gives you out, it's a painkiller, if you have a headache or a back pain, here's a treatment for your headache or back pain, they should do everything they would do to enhance the placebo effect of a real placebo, namely empathic and positive communication, which is responsible for the response to real placebo. They should add those. Because people don't focus on it, they think, now this is fluffy, esoteric, soft stuff. They don't focus on it, but there's hard science for it. And placebos and placebo effects, therefore, have been studying more than any

other treatment in the history of medicine. So I would say it's unethical for doctors not to induce placebo effects to the best of their ability. This is not enough to help them with another treatment to the best of their ability. And in some cases, like post-operative pain, the best option is an open label or a mix of open label slash honest placebos with real drugs. And you touched on just there the idea of a placebo surgery. Could you go into that a little bit more? Yeah.

So I'll tell you a true story. There was a guy in Boston. He had a fracture in one of his vertebra. So a fracture means a breaking, obviously. And the common treatment for certain spinal fractures is vertebroplasty, which means they take a big needle, inject some glue, cement, and glue it together. He did the procedure. He came back three weeks later for a checkup to see,

and the doctor did the procedure realize he had injected the wrong vertebra. And it still worked. He said, whoa, this is crazy. So then he did a placebo-controlled trial where he would take some people with the vertebral fractures. randomize them to get the real vertebroplasti, the real injection. Otherwise, just get the needle stuck in, nothing came out, just needle stuck in blank needle, placebo. The placebo worked just as well.

So why shouldn't that become the standard treatment? Why don't they just call that minimally invasive surgery? Because, of course, the placebo surgery that just has stick the needle has almost no side effects, certainly way fewer side effects than the real vertebroplastity, because the glue can leak and so on. So if you want a cure for your vertebral fracture that has a same chance of success, but lower risks, you've got to go with the so-called placebo surgery. Now, I've called a placebo surgery in this conversation just now, but in my book, I argue, it shouldn't be called placebo surgery because it's not the same as, let's say, a sugar pill, where the sugar in the pill

has no effect whatsoever, whereas the needle ponderating the skin does induce a physiological reaction no matter what you have subconscious or conscious beliefs are called the wound healing cascade, which leads to more blood, more tissue, white blood cells, et cetera, to heal it. But nonetheless, we don't get bogged down in terminology. Some people still want to call it placebo surgery, but just for the record, it shouldn't be called placebo surgery. They should call it minimally invasive surgery, which works via self-healing mechanisms. They can explain it that way to the patients.

And given it has the same benefits, less harms, it's crazy not to. I think I'd go for it. You know, it doesn't work. Sure, give me some. meant after, but I try that first. So I guess there is that argument of placebo being maybe the first choice, and then if someone does that and they find that there is no success there, there is still the surgery possible to them afterwards. Yeah. In general, though, you want to go with the treatment with the best balance of benefit and harms. Sometimes, in the case of this so-called sham surgery,

you have benefit-harm ratio is better. There's other examples of so-called placebo surgery for knee arthroscopy where, you know, they see the damage in the knee. The meniscus is torn and so on, they do something called lavage, they put them, clean it up, and it seems to work for many people, but a famous surgeon in Houston called Bruce Mosey, he was a certain for the Houston Rockets in the U.S. in that area, everyone would have seen him sitting alongside the team on TV the way, you know, here in the UK, the Manchester United team would be some of the physio might be known. They're sitting along there with the players. Half the people got real arthroscopy, half got sham, just the Midian's Siam.

decision and so to back up. They thought they got the real one. It worked just as well, even over a long period. These people have had serious knee pain. It was so bad, they didn't respond to maximal drug therapy for at least several months. So it's not a trivial effect size. The evidence suggests that the less invasive, so-called sham surgery, is as effective but with fewer harms. So go for it. No one goes to Hank's for spreadsheets. They go for a darn good pizza. Lately, though, the shop's been quiet. So Hank decides to bring back the $1 slice. He asks Copilot in Microsoft Excel to look at his sales and costs. Help him see if he can afford it. Co-pilot shows Hank where the money's going and which little extras make the dollar slice work. Now Hank says a line out the door. Hank makes the pizza.

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So opposite the placebo effect is this idea of the nocebo effect, where inactive treatments, they can worsen symptoms due to the negative expectations of it. Yeah. Is this an area that I guess is studied just as much, or is this maybe a little bit more of a side thing that comes alongside of it? The research is growing, but it's all but ignored. So people think it's okay to tell the truth in any way I want. So you're giving a paracetamol because you had headache.

By the way, just go read all the side effects. It costs 50p wherever you want to buy. If you read all the side effects, you wouldn't touch this stuff, bleeding, nausea, all this stuff. So sometimes in clinical trials, potential participants are forced-fed. These negative things might happen to them. This could actually cause the negative things to happen. But before I tell you the data there, the boring numbers, true story, 29-year-old builder jumped down from a platform, landed on a 15-centimeter nail that penetrated

his boots from the bottom up. He went to the doctor. They couldn't even move the nail. They'd give him fentanyloth, very strong painkillers to be able to remove the nail. And this is a 20-year-old, a builder, you know, probably generally tough people. And they end up giving him fentanyl, removing the nail slowly, took up his boot. Turns out the nail had gone between his toes. It hadn't penetrated his skin.

But he believed that it was painful. So it was painful. Pain is subjective partly. And this experience is dramatic, but there are many less dramatic examples. So in my data, I studied 250,000 people, all of whom received placebos in clinical trials, and half of them reported at least one side effect. But the sugar bill didn't cause the side effect. What caused it?

Well, it wasn't all nocebo, first of all. It's a bit more complex in the following way. If anyone were to ask you or I, if we have any symptoms of anything, do you have any nausea, any headache, any back pain every day for three weeks or five weeks or six weeks? Sometimes we're going to say yes. If we're in a clinical trial, our symptoms, headache, back pain, could be attributed to the trial drug, in this case, a placebo.

But to rule that out, we did a deep. deeper analysis that I won't bore anyone with, but they're happy to read the paper. We also looked at what happened in those trials that there was a no treatment group. There was no question of misattribution because you control for that. And about one third of these side effects and people taking placebos are nocebo effects. Telling patients about what the bad things that might happen is good. What we're saying is you're going to tell them in the right way and balance it with correct information about the potential benefits to not create this fear.

statistically there's a 33% chance that you'll feel some sensation in your tummy area if I just tell you the last thing you ate causes mild nausea. One and three people in your situation will report some sensations. And that's without me kind of having a white coat on and saying it very seriously and giving you some, you know, Latin terms to make it sound scarier and so on. So we've sort of spoken about this idea that when people experience a placebo effect, it's very much influenced by what's going on your head and the way that things have been, I guess, fed to you or explained. For people who, let's say, don't have as much trust in the effectiveness of medicine and maybe have a preference for natural alternatives,

is there any, I guess, correlation between those kind of people and the effects of placebo? Do they tend to fall off because of that lack of trust? Good question. The placebo community has been seeking to identify characteristics of people who are more likely to be responders. And most of my colleagues, they're usually better educated, they think, oh, no, following for that with tricks are way beneath me, but that's not the case. There's no correlation between IQ and it seems education. And again, it's because of our prior experiences, that the drug companies could predict who would respond to placebos, they'd rule them out of the trials. Because if the drug effect

is the drug effect versus the placebo effect, if you can reduce the placebo effect, you'll have a bigger drug effect. So it's in their interest. They got a lot of money, and they haven't figured it on either the proof they've not figured it out is they have what's called placebo run-in periods before trials. Before they do the trial of the drug versus placebo, they'll give everyone a placebo for a few weeks and see who responds to the placebo and rules them up. That's empirical. That's not based on any kind of test to see if you are naive or not naive or have a PhD or went to Oxford or Cambridge. None of that stuff seems to make a big difference. When we've spoken about the surgeries and, I guess, the pills as well, we're talking about this in, I guess,

the first period afterwards, but for example, someone who had a placebo surgery on their spine, does that tend to work long term where someone, you know, months, years down the line, is still feeling the success of placebo surgeries? Great question. And there's two answers to it. First of all, not all drugs have long-term effects either. I mean, if you take an ibuprofen pill, it lasts a few hours. So we shouldn't expect that placebo effects last longer than drug effects. In these trials, follow up with six months and a year. So it's long-term follow-up. So they can work for an extended period of time. And if we, I guess, began to understand the underlying neural basis of the placebo effect or

the placebo itself? They do. They do. They understand it. So is that something that we could then develop, I guess, something like brain computer interfaces to directly activate that? Or have we been able to target it and give that push that you can activate it without any kind of intervention? Great question. I don't know. I don't know. I don't know the answer. In theory, there's no reason why you couldn't. And they have done some fascinating studies on placebo mechanisms, so that placebo has been studied most frequently,

but not exclusively in the context of pain. And the way they discovered the mechanism for pain placebo effects is they gave a bunch of people placebo who had pain, but some of them they gave Neloxone, which is an opioid antagonist. It prevents the action of opioids. and those who had received naloxone did not experience placebo effects, which showed, and that that's been replicated, that showed that the placebo works by activating the body's

endogenous opioid system. So endorph, the word endorphin just means endogenous opiates or endogenous morphine that your body makes by itself. And for this conversation, we've been talking about placebo very much in the aspects of medicine and surgery and health, which obviously make sense, where it's, the research is based. But how much does placebo apply to other areas? I mean, for example, if you were able to induce the placebo effect when you're talking about skills or exercise or something like that. If you move away from the narrow conceptualization of placebo pills to kind of placebo effects, you don't need placebo pills to have placebo effects. And a seminal study in that area was in Italy. Post-operative patients were,

connected to an IV line, and only half of them were told they were receiving a powerful painkiller to reduce their pain, and those who were told needed a much less morphine to reduce their pain. So you're saying how does this work outside this? To me, it's clear. So it's a positive message, essentially, a positive message from someone you trust who delivers it in an empathic way. So I call positive empathic message is what accounts for placebo effects. That's what I focus on in my current role. We're changing the medical school curriculum so that empathy is at the heart of what the future doctors learn. So exercise, let's say, you know, what sport do you do, Alex? I climb, I run. Yes, what's your best 5K time? I've not done 5Ks in a long time. Uh, 25. Yes, what if I told you,

you know what? I've just been studying, you've been watching you run. You can do 2430. Just me saying that can lead to you doing 2430. And the proof is Roger Bannister broke the foreman at my They thought it was humanly impossible for a human to break the four-minute mile. They thought it was a kind of a natural limit, like the speed of light or something. So his coach didn't even tell him what he was trying to coach him to do, that he broke the four-minute mile at the Iffy track in Oxford. Then within a few months, 13 other people broke the four-minute mile because the mental barrier had been cracked down.

You can exaggerate it. People think positive thinking, oh, yeah, positive thinking all of a sudden, I'm going to have a billion pounds in next week. And so that's just BS, frankly. but because people don't really believe in it and it's unrealistic. But before anybody does something, by definition almost, they've thought about it. They visualize in somebody that they can do it. Like before someone walked on the moon, someone thought about walking on the moon.

Things happen in our minds before they happen in reality. And to catalyze that passage from the mind to reality, someone we trust saying, yes, you can do this. Certainly, I think that everyone you speak to would have a personal experience to relate, that shows that to be the case. I mean, there is also this idea that I think quite a lot of people aspire to is the affirmation of the self. And I wonder if that plays into placebo as well if you're doing it to yourself. Yeah, because self-plicebo.

That's an area I'm very interested in because that has a wide application. And there are some trials. It's a nascent area. Let's say you want to put yourself in a better mood. What do you do? Do you give yourself empathic positive messages? That's all part of it, I think. I think, for example, people have dogs.

We treat our dogs better than ourselves. I mean, my dog used to go to open the peanut butter thing and eat the peanut butter. I get upset for a few seconds, then it would be forgotten. But if we make a mistake, we can remember for 10, 15, 20 years and even have therapy for a long time, because we can't forgive ourselves. You can't change anything in the past. You can be a better person now and forget about us. I think that the same things that we tell doctors to do to enhance placebo effects,

we can and should do to ourselves and it has an effect. What I recommend to people, individuals who want to enhance placebo effects is the easiest way is to just stop the negative stuff. So we have our breaks on. People have studied how many thoughts we have in our heads. They can't count them because it's hard to distinguish sometimes. There's a blurry line. So what is one discrete thought is hard to isolate? But there's tens of thousands in a day.

No one disputes there are many, many of them. We're not in control of them. They're mostly negative, unfortunately. I should have done this. I shouldn't matter. I don't like this person. I don't like that person. To get out of that space, the fastest thing to do is altruism, do a random act of kindness.

Just say something nice to someone, and that takes you out of the negative frame of mind, the nocebo area, into the placebo area. Then you can move to positive thinking, but the move to positive is difficult because people don't believe it. I don't really believe I can do 50 push-ups. They don't really believe it, so saying it becomes a dissonant. Just move into neutral by doing a random act of kindness, take yourself out of the space, and you're doing something nice for somebody. In your research writing for your book, and I mean your research in your whole career,

what's been the thing that's really struck out to you about the placebo, placebo effect, the whole industry? Three things. One is it's not just for so-called psychological things. The placebo surgery, or so-called placebo surgery, works for mechanical things. Secondly, honest placebo's work. That was surprising to me. Third of all, I thought, because I've always been interested in taking this research,

from within the walls of academia to outside the real world. The main argument in the book is that it's time for placebo researchers to stop doing research on the mechanisms. We already know how it works. Get out there. Let's get this knowledge out there for people to benefit from. So when we do that, we teach doctors to offer more empathy to patients because this is one of the reasons why the sugar pill might work. And I thought that the side effect would be that doctors would become burned out. If I'm too empathic, everybody all the time I'm going to feel burned out. In fact, the opposite is true. The more empathy the doctors offer, the more they try to elicit placebo effects, if you want to call them that, the better their well-being is. We don't know fully, but the reason it's going to be

summarized by what Victor Franco said. Victor Franklin, of course, was tortured in the Nazi war camps, and he claims to have found his ultimate freedom. And he said, if you have a why to live, you can deal with almost any how. So when doctors are trying to help patients, they really see, You know, you're making a patient happier, instead of just focusing on the tests and protocols and so on, which is important to when you're focusing on and observing and connecting to the healing of the patient, this creates resilience,

enables you to deal with the difficult job you have as a doctor because it is hard to being a healthcare practical heart. Thank you for listening to this episode of Instant Genius. That was Jeremy Howick talking about placebos. The Instant Genius podcast is brought to you by the team behind BBC Science Focus magazine, which you can find on sale now in supermarkets and news agents, as well as on your preferred app store.

Alternatively, you can come and find us online at sciencefocus.com. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name audio believes you can have digital precision with analog warmth. Alongside French acoustic specialist vocal, Name creates high-end audio systems combining innovation with craftsmanship

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