Science Vs - Placebo: Can the Mind Cure You?

Episode Date: June 2, 2022

[REBROADCAST] Could fake medicine actually take away your pain or treat a disease? We dig into the science of placebos to find out more about the power of the mind to heal. We speak to medical researcher Prof. Ted Kaptchuk, neuroscientist Prof. Fabrizio Benedetti and medical psychologist Prof. Manfred Schedlowski.  Check out the full transcript here: https://bit.ly/3xaPKM3  This episode was produced by Wendy Zukerman, with help from Rose Rimler, Meryl Horn, Kaitlyn Sawrey and Michelle Dang. We’re edited by Blythe Terrell. Editing help from Caitlin Kenney. Fact checking by Michelle Harris and Erica Akiko Howard. Mix and sound design by Bumi Hidaka and Peter Leonard. Music by Peter Leonard, Emma Munger and Bobby Lord. Recording assistance from Fabian Mirko May, Mary Dooe and Maggie Penman. A huge thanks to all the scientists we got in touch with for this episode, including Dr Diletta Barbiani, Dr Cynthia McRae, Dr J Bruce Moseley, Professor Apkar Apkarian, Professor Jon Stoessl,and others. And special thanks to Lynda McKenzie, the Zukerman family, and Joseph Lavelle Wilson Learn more about your ad choices. Visit podcastchoices.com/adchoices

Hi, I'm Wendy Zuckerman and you're listening to Science Versus from Gimlet. This is the show that pits facts against phony medicine. On today's show, the placebo effect. We like to turn our noses up at the placebo effect. Because the idea that someone can feel better from a pill that has no actual medicine in it, it sounds kind of ridiculous. Like, how is that possible? But years and years of scientific research has shown that the placebo effect really works. And it works for all kinds of people. People like... Oh, my name is Linda.

This is Linda Bonanno. When we interviewed Linda a few years ago, she told us about this condition she'd had for years, irritable bowel syndrome, and she said it was awful. To me, it was like your intestines twisting real tight, tight like a rubber band. Sometimes two days straight, I'm sick with it. Irritable bowel syndrome, or IBS, is really common.

It's where you can get horrible stomach pains, diarrhoea or constipation, and it can be completely debilitating. With IBS, you never know when you're going to be sick. You could be OK one minute and then all of a sudden it just starts up. Linda tried everything. Pills, diets. Change this, change that.

No, nothing. Absolutely nothing was helping. But then one day she saw an ad on the telly for an exciting new IBS study. And I says, well, you know, maybe I should, you know, call them up. Maybe they can help me out. So she called the number on the screen and got into this trial at Harvard Medical School in Boston, where a doctor handed her a bottle of pills. It's just a capsule pill.

It's got like the powder inside. Now, as you might have guessed, that powder, it's no cutting edge medicine. It's a placebo. There's no active drugs in it at all. Linda goes home. She takes the pills. And for the first few days, nothing changes. And then the fourth day, that's when I realized my pain was all gone. I said, well, maybe it's

just my imagination. I says, it'll come back tomorrow or the next day. Well, before you know it, it's seven days, it's 10 days, it's two weeks. I was in shock. I said, nah, this can't be. All of a sudden, there's absolutely nothing. Absolutely nothing. I'm talking about gone with nothing, not one symptom at all. I'm waiting around for the pain to come back, and nothing's coming back. And this is the wild effect that placebos can have. You take a pill with no actual medicine in it, but you feel the benefit anyway.

OK, so that alone is pretty strange. But what happened to Linda was even stranger. Because from the very start, when her doctor told her to take those capsules with white powder, he actually told her that this wasn't real medicine. He told me it was a placebo. It wasn't a medication. I thought, what?

Linda was part of the first randomised control trial that told patients, we're giving you a placebo. This is basically a sugar pill. And it involved around 70 people who had had IBS for a while. It compared Linda's group, who were taking placebos and knew it, to those who just kept doing what they were doing. And on average, the people who were taking placebos had fewer symptoms

than the other group. I said, this can't be. I'm sick for 10 years. I take placebo pills and for three weeks I have no problem whatsoever. It's shocking. It's like I can't make sense of any of it. I don't understand any of it. Today on the show, we're revisiting one of our most popular episodes to try to make sense of what happened to Linda. And we're going to dive deep into the world of placebo to answer the following questions. One, what can the placebo effect help with? Two, how does it work?

And three, what are its limits? Like, is it possible to harness the placebo effect so that we can stop taking some medicines altogether? When it comes to the placebo effect, there's a lot of... What? But then there's science. Science versus the placebo effect is coming up just after the break. Bumble knows it's hard to start conversations.

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Think of it as your guide for all things AI, with the most human issues at the center. Join me every Wednesday for Pioneers of AI. And don't forget to subscribe wherever you tune in. Welcome back. We've just heard the story of Linda, who had irritable bowel syndrome for a decade, took placebo pills, and even though she knew she was taking fake medicine, she got better. So we called up the scientist behind this experiment. Okay, this will be fun. to find out more about the weird world of placebos. My name is Ted Kaptchuk.

Ted is a professor of medicine at Harvard University, and he told us that when his study worked, he was shocked. He wasn't even sure how to describe it. It's, like, unbelievable. I didn't know what to write. I didn't know what words to put into the paper. I had no idea how to explain it. It's like unbelievable. I didn't know what to write. I didn't know what words to put into the paper. I had no idea how to explain it. It's still hard to believe. He was so surprised because this experiment flew in the face of everything that scientists thought they knew

about the placebo effect. And to fully understand why it's so surprising, we're going to leave Linda's story for now and take you back to a time before scientists were studying the placebo effect. Let's start our story about a century ago. So cue the flapper music. Perfect. It's just after World War I. There's all these advances in technology and chemistry

and lots of new drugs are being doled out. Good advice. When your digestion is upset and you feel headachy and irritable, take Carter's Little Liver Pills. Groves emulsified nose drops will surprise you with the way they look and act. Over the next few decades, we got all these wacky-sounding drugs, but also new medicines that seemed much more legit, like drugs for depression and new painkillers. And often patients were feeling better soon after taking them. But in this mix, some scientists started to wonder

that maybe there were times when people were getting better not because of anything inside these snazzy new drugs, but because of something else. Like maybe it was a coincidence and these people were going to get better anyway. Or maybe it was the power of suggestion. Like just having your doctor tell you I'm giving you a brand new medicine made you expect that you were going to get better. In other words... Expectation is a form of mind cures. Like, if you think you're going to get better,

if you believe you're going to get better, if you expect to get better, you're going to get better if you take that pill. And by the 1950s, you start to see more and more scientists putting this idea about expectation to the ultimate test. They did a bunch of studies where they got a group of patients and gave them state-of-the-art medicine, while another group got a placebo, say, a sugar pill.

And the scientists ultimately wanted to know, did the drugs win? If the medicine was better than a placebo in a randomised clinical trial, it was legitimate. If it wasn't, it was the dummy prize. It was bogus. It was fake. Quite a lot't, it was the dummy prize. It was bogus. It was fake. Quite a lot of medicines were getting the dummy prize back then. That is, placebos were working about as well as a bunch of drugs on the market, like tranquilizers

and painkillers. And the fact that the placebo effect was so powerful triggered a reckoning. The FDA took notice, and in the 1960s, they brought in new rules to say that if drug companies now wanted to get a drug on the market, they had to show that it was better than a control, like a placebo. And for decades, this is where placebos lived,

in the land of clinical trials. And very few people were thinking that maybe placebos could be medicines in their own right. It's been ignored or maligned. It's been put into the dungeon of medicine. Only relatively recently have scientists like Ted freed the placebo effect from its dungeon to see how powerful it really is.

And so we wanted to know, what have they found? Well, now we know that the placebo effect is not a panacea. Some things aren't really affected by it. Like, you can't kill an infection with a sugar pill. Here's Ted. Placebos don't cure malaria and don't shrink tumours. But they've also been finding that placebos really can help with a bunch of different things.

Pain, dizziness, fatigue, anxiety, depression, nausea, those kinds of symptoms, the placebo effect can mimic and often rival good drugs in randomised controlled trials. There are also studies showing that fake surgery for back or knee pain can relieve pain about as well as some real surgeries. That is, doctors have taken a bunch of people with painful knees, given them an anesthetic, cut them open, basically twiddled their thumbs for a little, and sewed them back up. Then they compared their pain to a group of people who got real surgery. And...

In those studies, the real procedure was no better than the placebo treatment. Wow, so people can wake up and they have like a little scar, but nothing's actually gone on. And it's really bizarre. The fact that fake medicine can do anything to help with these complicated conditions like knee pain or Linda's irritable bowel syndrome is really impressive. And it got scientists like Ted wondering, how is this working? Like what on earth is happening in our bodies that we take placebos and feel different? And here's what they found. When people take placebos and feel different. And here's what they've found.

When people take placebos, it can cause real biochemical changes in their body. We know that many times when people respond to placebo, the brain releases neurotransmitters like endorphins, dopamine, that actually change the experience of symptoms. So, for example, there are studies that find you can take a placebo painkiller and your brain can actually release endorphins, which are like the body's natural painkillers.

And brain scans show that parts of the noggin that control pain flicker differently when someone's on a placebo. Producer Rose Rimler asked Ted about this. So your brain's pain control centers light up and your brain juices start flowing. That's a good way of saying it, and that's not technical. Yeah, I like it. They light up or sometimes dim down, but they change.

They're engaged. There's also some evidence that these brain juices can have larger effects throughout our body. Like one study found that when people took placebo painkillers instead of opioids, it didn't just relieve pain but could also lower their heart rate. So scientists are seeing all these cool changes in the body when people take placebos. And they figured that this was tied to expectation. Like a doctor tells you,

I'm going to give you pills that will make you feel better, and then you do. The assumption is that if you have a placebo effect, it's expectation. And other scientists we talked to agreed that expecting you're going to get better from a drug does seem to be an important part of how the placebo effect works. But several years ago, Ted and his team did some surveys of patients in placebo trials,

and it turned out something weird. His team found that patients actually often didn't expect to get better. At first, he was like... What do you mean you don't expect to get better? All the patients that we interviewed said they didn't expect to get better because they'd been to 10 doctors already. And the thing is, despite not expecting to get better when they took a placebo, some of them just did.

So Ted wanted to see what would happen if patients didn't expect to get real medicine. Like, if you just told patients outright, I'm giving you a placebo. Ted went to a mate of his who studies irritable bowel syndrome, and he said... I wanted to be totally honest, no deception, no concealment. And he looked at me and he said, Ted, this is the craziest thing you've ever told me.

Let's do it. And all this led Ted to do that study with Linda, which, as we said, worked. On average, people who got placebo pills knowing they were fake felt better, which is weird, right? Because Linda had taken lots of pills, like real medicine. So how did a placebo work better than them? Why didn't, because she had been taking other medications and she.

Oh, she took everything. Yeah, yeah. She took everything. So why wasn't she. I don't understand it. In our studies, people come in with six bottles of pills. I'm taking this, this, this, and this. So Ted, why is this pill different than all the other pills they've taken?

You know, I don't know either. And since Ted's trial, more and more studies are finding that when people are told they're given a placebo, it can still make them feel better. And not just for IBS, but other stuff, like migraines and even hay fever. Wait, so then how is the placebo working if it's not, I'm expecting to get better?

You're asking questions that are at the cutting edge. I think that the placebo effect works on it automatically, right? You don't have to think you're going to get better. You don't have to believe you're going to get better. You don't have to expect you're going to get better. In Romeo and Juliet, if you watch it for the 10th time, but it's a good performance, you start to cry. Your hair goes up.

It's automatic. It's what you feel and what your body enacts. That is crazy. It's totally crazy. In a paper written in 2021, Ted and his placebo buds wrote that in most medical situations, there is this inherent hope that you might feel better. But there's also some uncertainty that perhaps nothing will happen. And they suggested that maybe that mixture of feelings comes together to produce a shift,

quote, automatically and non-consciously, end quote, that somehow changes how we perceive pain. But after the break, the placebo plot thickens as we go on an adventure to the Alps. You're late! Coming up after the break. Welcome back. We've just found out that the placebo effect can be powerful.

And while we thought for a long time that this was largely driven by expectation, people believing they were going to get better, and so they did, new research is telling us that something else might be happening here too. To find out more, we need to go on an adventure to the Alps. YOLO, YOLO, HEHE! There is a lot of snow, a lot of ice, everything is white. This is Fabrizio Benedetti,

a professor of neuroscience at the University of Turin in Italy. And he spends a lot of time around the Matterhorn. Usually we ski a lot as well. We are good skiers. That's the reason why we are up there, actually, not for working, but for skiing. I'm joking, of course, I'm joking. So Fabrizio runs a laboratory up on those mountains that he loves to ski on. It's more than 11,000 feet, or 3,500 metres, up. And Fabrizio is here because when you're up so high, it's hard to get enough oxygen into your lungs.

And if you're not used to it, that can lead to altitude sickness, headaches, dizziness, fatigue. Sometimes there is vomiting or nausea. Nothing like a cheeky vom before you hit the slopes. And so, at the edge of the earth, Fabrizio wanted to know the edges of the placebo effect. He is helping to uncover a new way that the placebo effect is working. And here's how he's doing it.

Fabrizio brought a bunch of people up into his laboratory and put them on a stepper, making them do 3,000 steps. You know, when you step on a stepper at high altitude, it's pretty painful. Without enough oxygen, people got tired really quickly. Their muscles started to ache. And so Fabrizio told them, I'll give you some oxygen to help.

The people in his study have these bulky oxygen masks on and so Fabrizio flicked on a machine which makes a noise like oxygen coming out of a tank. Yeah, it's a sort of weasel. It's a sort of buzz. And as you've probably cottoned on... The oxygen tank is empty. There is no oxygen inside. After all this, Fabrizio found it didn't work.

The brain wasn't really fooled. Those painful headaches, they stuck around, which meant the body couldn't create oxygen out of thin air. But Fabrizio thought, what if we added a little more trickery here? OK, so here's what he did. He set up a new experiment, got people back on the stepper and told them, I'm going to give you real oxygen. The sound came on, but this time he actually gave them oxygen.

Their headache goes away and he repeats the experiment. You give oxygen the first time, oxygen the second, the third. But then on that final time, he switches it up. That is, he turns on the machine, but no oxygen is coming out. And guess what? What is really surprising is that fake oxygen works. Fake oxygen took their headaches away. That's crazy.

Yeah, yeah. That's really surprising. Not only did the headaches go away, but Fabrizio also took some spit samples throughout this experiment because he wanted to find out if the people didn't just feel better, but also if he could see changes throughout their body. And he could see changes throughout their body. And he could. So usually altitude sickness unleashes certain chemicals in the blood

which can lead to headaches. But the people in this experiment didn't have a bump in these headache chemicals. And what Fabrizio is doing here is creating a placebo effect through a process called conditioning. It's where you condition the body to connect something, say, an oxygen tank, to getting real oxygen. And over time, your body creates such a strong association subconsciously

that just hearing the oxygen tanks makes your body respond as if it's getting the real stuff. This is what Pavlov and his successors did all those years ago with the dogs. They got them to associate stuff like a bell with food. Until all it took was a little ring of the bell, and ta-da, the dogs were salivating. And while researching all this for this episode, I read this awesome book by Joe Marchant called Cure.

And this pointed me to a totally different group of studies that were using conditioning and the placebo effect, but in a different way. A way that made it so clear that the placebo effect can sometimes work subconsciously. And some scientists want to take these ideas and use them to change how we do medicine. So, here we go. Here we go. Let's do this. This is Manfred Schedlowski, a professor of medical psychology at University Klinik Essen in Germany.

And Manfred started researching the placebo effect because he has a big dream. We have a vision that the patients do not have to take so many drugs started researching the placebo effect because he has a big dream. We have a vision that the patients do not have to take so many drugs. Yeah, so Manfred is in placebo research because he wants to help people cut down on the amount of medicine they have to take. Like, he wants to harness the powers of conditioning so that people feel the benefits of a drug without the bad stuff. That we can sort of use this to reduce the toxic

and unwanted side effects of the drug. And here's how this would work. Manfred would condition people's bodies to associate their medication with, get this, not an oxygen tank or a bell, but a weird drink. It's a sort of strawberry milk with green colour and a drop of lavender. A drop of lavender. So this weird drink he uses, it looks like bright green milkshake, tastes of strawberry and smells like mothballs. Do you like the green drink? Do you drink it? No, it's awful. It's completely unusual. It's an unusual taste. Completely unusual. And why was it important to find such an unusual concoction? Well, Manfred couldn't use anything that people might already have associations with,

like milk, which you might associate with childhood, or coconut water, which you might associate with being a wanker. Manfred and his team needed a clean slate so that he could kind of teach our body to associate it with whatever he wanted. In this case, medication. Yeah, yeah, yeah, yeah. This is exactly true. Yeah.

What Manfred is trying to do is to get people's bodies to react as if they're taking a drug, when really they're just drinking his weird drink. He's been testing it out first in healthy people, around 150 of them. And he's using a drug which has a really clear effect. It's something that suppresses the immune system. So Manfred gives people the weird drink along with a pill. So we repeated this drink-drug combination four times.

Then he gives them the weird drink, but this time no medicine. That's right, no drug, no sugar pill, just the drink. And it worked. The brain was saying, hey, I remember just the drink. And it worked. The brain was saying, hey, I remember this weird drink. It means time to suppress the immune system. And off it goes. It's lowering their immune system. That's crazy.

Yeah, at a glance, it looks a little bit weird. Yeah, I absolutely agree. However, it's really sort of neuroanatomy and neurochemistry. In other words, it's science. Since this experiment, Manfred and others have found that they can use conditioning to mimic the effects of other drugs. Like one team found that you could condition the body to make more insulin, which is bonkers.

And this is some of the strongest evidence we have that the placebo effect can be happening subconsciously. Because you can't just think to yourself, hey body, bump up my insulin levels and see it happen. And in 2021, researchers used a similar approach, but with opioids. Here's what they did. They got a bunch of patients who just had spinal surgery, which can be super painful. And one group was told to take their opioid meds alongside a placebo pill. And they were told these are placebos. Now, at first, they had to take a placebo pill each time they took an opioid.

And basically, the researchers were conditioning them to associate the placebo with the opioids. But after a few days, they were told, you can keep taking your opioid-placebo combo as you need to. But on top of that, you also have to take the placebo on its own three times a day. About two weeks later, the researchers looked at that group and they found that if they kept popping these placebo pills, they ended up downing fewer opioids than a group that was just given the opioids, none of this placebo madness. And they ended up downing a lot less opioids, 30% less. So this is all pretty promising. But we are still pretty far away from Manfred's big vision. He's in fact already hit some stumbling blocks. One problem is that the drink that he's made,

on its own, it's not quite as strong as the drug. Another thing is that the effect doesn't seem to last that long. So your body kind of loses the association between the drink and the drug. Now Manfred is researching ways to keep it going for longer. And this is actually a problem with a lot of the research into placebos. We don't have long-term studies, so we don't know how long the placebo effect can last. Generally speaking, we're in the early days of studying placebos. So even though there is a long way to go, it's still pretty cool to think of where we are.

I mean, 20 years ago, when Manfred started this research, people thought he was kind of nuts. In fact, after Manfred told someone his ideas, they told him. We have to become an artist that has nothing to do with science. And so now, how is your work accepted? Now this is very well accepted, so that was good. So when it comes to the placebo effect, what do we know? While the placebo effect is not a panacea, it's been shown to help lots of people with lots of different conditions. And what we're learning is that placebos work in all kinds of

ways. One placebo effect is probably due to expectation You take a pill expecting you're going to get better And so your brain releases stuff like endorphins To make you actually feel better At other times, conditioning might be playing a role But then there's what happened to Linda Our patient whose irritable bowel syndrome got better on placebos And all of a sudden you take a sugar pill And all the symptoms are gone?

I couldn't believe it. For her, this wasn't quite expectation. After all, she didn't actually expect to get better. And it wasn't clearly conditioning either because it's not like she had any associations with getting a pill and then feeling better. If anything, she'd taken all these pills for years and was feeling better. If anything, she'd taken all these pills for years and was still sick.

But these conditioning studies have opened the door for the placebo effect to work subconsciously. So maybe that's what's going on here. Ted Kapczyk over at Harvard says we're still working it all out. I'd say, you know, the mystery of the brain is just out of control, what's going on. And, you know, so many neurons, galaxies of neurons just communicating with each other all the time. Unbelievable. Do we have a complete understanding of how placebos work?

No. Are there a lot of unknown questions? Yes. But something is going on. As for Linda, it kind of didn't matter that things are still a mystery here. Because the placebo pills worked. In fact, they worked so well that when the docs took them away at the end of the trial, her IBS came back.

So eventually, Ted gave her those placebo pills again. And again, she got better. Oh my God, I was the happiest person. I really was, not to be sick anymore. Ugh, I don't have to worry about a single thing. That's science versus the placebo effect. Hello? Hey, Michelle Dang. Science versus the placebo effect. Hello. Hey, Michelle Dang.

Hi, Wendy. How's it going? Oh, good, except the stand for my microphone just started falling down. It's all good. I've worked it out. I'm a professional. How are you, Michelle Dang, producer at Science Versus? I'm good. How are you, Wendy? I'm doing good. How many you, Michelle Dang, producer at Science Versus? I'm good.

How are you, Wendy? I'm doing good. How many citations in this week's episode? This episode has 116 citations. And if people want to see these citations, where should they go? Head over to our show notes, and there's a link to our transcript that has all the citations in it. And on Instagram this week? There is a lovely green drink on Instagram

that you may have heard of in this episode. If you want to see that, and we also have a diagram of the experiment in the Alps and a picture of the pretty mountain it's on. Wonderful, wonderful. So if people want to go there and see all that stuff, go to our Instagram, which is science underscore the S. If you have any questions about the episode, you can tweet me at Wendy Zuck. And that is all. Thanks, Michelle. All right. Thanks, Wendy. See ya. See ya. While we were updating this episode, we learned that Linda had actually died a couple of years

ago. She stayed in touch with Ted, though, and he told us that she'd taken the placebo pills for three years and didn't have any more IBS symptoms. He also said that Linda was proud to help other people with IBS by spreading the word about how placebos worked for her. This episode was produced by me, Wendy Zuckerman, with help from Rose Rimler, Meryl Horn, Caitlin Sorey and Michelle Dang. We're edited by Blythe Terrell. Editing help from Caitlin Kenny.

Fact-checking by Michelle Harris and Erica Akiko Howard. Mix and sound design by Bumi Hidaka and Peter Leonard. Music by Peter Leonard, Emma Munger and Bobby Lord Recording assistance from Fabian Mirko-May, Mary Dewey and Maggie Penman A huge thanks to all the scientists we got in touch with for this episode including Dr Diletta Barbiani, Dr Cynthia McRae, Dr J Bruce Mosley Professor Apkar Apkarian, Professor John Stossel and others. A very special thanks to Linda McKenzie, the Zuckerman family and Joseph Lavelle Wilson. I'm Wendy Zuckerman.

Talk to you next time. Just let me go for dinner. Okay. I need a real dinner, not a placebo dinner. Okay. Bye-bye. Have a nice day. Bye-bye. Thank you.

Bye-bye. Thank you.