1056: Placebo & Nocebo Effects | Skeptical Sunday

24:29This is why research is cumulative. Over time, we get more and more puzzle pieces and try to make sense of it all together. We need many studies on the same topic just to start and understand it. To be fair, if you eat three entire pizzas, you will definitely feel and possibly even look pregnant at the time, for sure. Personal experience here, over here, so trust me. Have it on good authority, good personal authority. But what actually physically happens in the brain and body? Expectation effects, such as placebo or nocebo effects, are no coincidence, nor are they just in our mind. On the contrary, they are based on complex psychoneurobiological processes in the brain.

25:12Psychoneurobiological is an awesome word. That is a$10 word right there. Yeah. Simply believing that a certain treatment is effective has been shown to activate mechanisms in the body that improve the treatment outcome. This can also be described as a kind of internal pharmacy of the body that everybody just carries around with them. For example, imaging techniques can be used to show that certain areas of the brain, for example pain relief systems, are activated during this process. In the field of pain therapy or pain research, the placebo effect has been particularly well studied. If a patient expects a remedy or medication to relieve pain, pain-relieving substances, known as endorphins are released in the brain and can even alter transmission of pain in the spinal cord.

25:59This relieves pain, for example, back pain or headaches, even though the patient has not taken a real painkiller. Wow. So are you saying that a sugar pill can make our spinal cord feel less pain? So this is interesting because it sounds like the placebo effect is not just the brain feeling the pain and being like, I'm not going to feel that because I took a tic-tac, but it's all over the body. The whole body is being juiced up with endorphins that are like, nah, we're not going to feel the pain because I got my puppets under my pillow or whatever. Yeah, exactly. In the study I just described, the authors found that placebo analgesia, so an inert treatment that allegedly reduces pain, actually reduced participants' pain, aka the placebo effect.

26:41That was measured by asking the participants to rate the pain they feel on a scale from zero, I feel nothing to 100. I feel everything and all of it. But it also led to reduced pain related activity in the brain and spinal cord. So does the placebo effect only work for pain? Because I worry that people are going to be like, I can cure everything with placebo effect. Let me dump my chemo meds in the toilet and go get a bag of puppets or like go get a stone to charge under the moon. People could take this too far, I think. Yeah, I completely agree. And we have to always be careful because some of these findings are very specific.

27:16So the spinal cord involvement study was quite unique to pain, but there's more if we look beyond pain. There's also research on placebo effects in mental health conditions such as depression or other physical conditions, for example, involving the immune system in the body. Studies indicate that the nocebo effect triggers processes in the central nervous system that can lead to physical changes. In this system, fear of pain can block opioids and inhibit dopamine, leading to increased rather than decreased pain. Really, they have effects on our whole body. Hormones, neurotransmitters, physiological responses, brain activity, etc.

27:57Wow, so you research all of that and you listen to every single episode of this show without fail. That's really amazing. Yeah, I'm a wizard. Honestly, I wish I could do even more, but my time is also very limited and I focus my work specifically on expectation effects in pain. But in the Treatment Expectation Research Center where I work, we collaborate with many different researchers in Germany and beyond to investigate the impact of patients' expectations on the efficacy of medical treatments in many bodily systems, chronic pain, depression, but also the immune system. We do experimental studies in healthy participants and also clinical studies with different patient groups.

28:38But some groups even do research on placebo effects in animals. I think it's really cool that so many people are researching this. And I'm very curious about the immune system stuff. That's a different show, of course, a different episode of this podcast. But if you can make your immune system stronger with placebo, that is incredible. I agree. That's a game changer. And I would love to talk more about that offline and see if there's another episode about that that we could do. That's awesome, fascinating, and hopefully real. Again, it's so cool that so many people are researching this stuff. Do these effects affect everyone in pretty much the same way?

29:13I'm guessing no, because bodies are so different and there's 8 billion of us. But, you know, how uniform is this? Yeah, so placebos work in general and in principle, but not for everyone and not for everyone in the same way. The effects can vary from person to person, symptom to symptom, and even disease to disease. Genetic factors certainly play a role, but personality traits could also be important. Some people are inherently optimistic, positive, and open-minded. They might respond better to placebos than somebody who is more anxious, skeptical, and critical. Oh, crap. Anxious and critical.

29:48I feel attacked, but go on. And also, did we just ruin the placebo effect for everyone with this episode? Like, sorry, your bag of puppets was working great last week, but now you know it's placebo, so you're not going to... no more benefit from you. You got to go out and get rocks now. Well, the good news is that individual expectations can change everything. So just change your expectations and you'll be good. Fine. The cool thing is that there can even be a placebo effect when patients know they are taking a pill without an active ingredient. This gives us an idea of just how powerful these mechanisms can be.

30:18That's actually really good news, right? And that was what you tried in the beginning of the episode, making me eat a Tic Tac and telling me it will still work against my headache, even though I know that Tic Tacs are just little literal sugar pills. Was that what that move was there? Yeah, exactly. That was what researchers call an open-label placebo. In other words, you know that what you're taking doesn't actually have any pharmacological substance in it. It is basically inert. This new concept is currently still being studied a lot. But from ours and other studies, we know that open-label placebos seem to work better when the person is in need of relief and has some kind of symptoms that they want to get rid of.

30:58In healthy young adults with nothing to improve and generally a nice lifestyle, it's actually not surprising that these effects are much smaller or even absent. There's even one step further, Jordan, imaginary placebos. Okay, before we get on to what that is, because that sounds like some Jedi stuff, I'm curious what you think. If I tell my kids that their gummy vitamins that they take at night will make them tired and sleepy, I mean, one, I know I'm just lying to my kids and calling it an open-label placebo, but I don't know, parents are with me. I might be okay with that. Do we think that might work or is it just mostly, again, with pain?

31:33I guess it would only be an open-label placebo if you told your kids that it is the placebo effect and they're not actually going to make them tired but if they believe in it, then it will do something. It would be more of a deceptive placebo if you tell them that it will make them tired but I think it could work so you should try it. I think I'm fine with deceptive placebos also because sometimes I just want them to go the f*** to sleep. All right. So imaginary placebos. Placebos are already inert and work anyway. Now they can also be literally imagined. How does that work? Yeah, that is apparently a thing.

32:06I also had a hard time believing when I read it first. Basically, when you take an imaginary placebo, you don't have anything physical that you ingest or apply to your body. You just imagine taking it. Like a kind of ritual you do every day where you imagine vividly that you are ingesting a pill, for example. And it is these rituals and learning experience that fuel placebo effect. So it's, I'm actually in the end, not super surprised that it works. If we have these ritual and these expectations, they can already fuel the placebo effect quite well. So you literally just pretend you're taking medicine.

32:43I'm drinking my medicine now with an empty hand, nothing in it. And that actually works? It seems so. First studies show, for example, that test anxiety in healthy students was lower in the groups who had taken either an open-label placebo or an imaginary placebo compared to a control group. The two placebo groups did not differ in their effects, meaning that they were equally effective in reducing test anxiety. But again, we need more evidence to make us believe these findings and not trust a single study that we read. Sure. It's so easy to trick ourselves, I guess. Let me ask you this. If I give myself, or someone else for that matter, a shot of vitamin and B12 or saline solution, like you said before at the top of the show.

33:26And I tell them, this is going to make you ace your exam because it helps your brain fire on all cylinders, something, something. And they're like, great. I give them the saline solution, the injection, right? We're already talking about invasive. What if it's something that gives them a little bit of like a niacin flush too? Like there's another effect linked to it that they can feel and see. They're like, wow, I'm really warm. This stuff's really working. Does that increase the placebo effect? because they're actually getting like a pharmacological result, even though it's not the same result that they're going for.

33:56Like them being warm is not going to help them ace the test. Them being warm is a side effect of, I don't know, niacin or something that's in that shot, or B12. Does that increase the placebo effect of them, I don't know, feeling better as well? Does that question make sense? That was all over the place. Yeah, it totally makes sense. And I'm glad that you asked it because it does. And these placebos are so-called active placebos. It means that you get something that is supposed to, for example, have a pain relieving effect, or it's going to make you be more concentrated at an exam, but it also has a side effect.

34:29I remember a study where the side effect was like a little burning in the nose. They got a nose spray that was supposed to make them feel less pain. And actually people felt less pain because the side effect that they felt made them more confident and believing in the fact that they actually took something that is going to help them. That's what I was thinking, because they might go like a shot that makes you better an exam. That's not a real thing. And then it's like, oh, crap, this is burning a little bit. I guess I am taking the limitless pill here or the I guess I did get a magical injection from Jordan.

34:59It just seems like that would work on me, I think, is why I kind of came up with that. Right. And I know that pre-workout stuff, for example, you take these pre-workout things that are just like usually loaded with caffeine. But if they also include other stuff that makes you feel flushed or turns you red, you really do feel like you are on, you're just ready to do your one rep max in the gym or something. And I feel like they add that in there to enhance the psychological effect of this pre-workout stuff. And probably because it's a cheap way to make something look like it's working or feel like it's working.

35:33Yes, that's completely true. And in the case of the protein that you're taking before the workout, I guess that's kind of like an open-label placebo or at least has an open-label placebo effect to it. But if I would give you the nose spray and you'd feel the burning in your nose, that would be called a deceptive placebo. Is that even allowed, like not telling people the whole story? I'm not saying, you know, me selling that in law school, which I didn't do. I kind of regret not doing it. Me selling that in law school, that's obviously not allowed. But what about the ethics of research or medicine?

36:01Because I think it's a good thing because you're telling patients that are going to undergo, I don't know, chemo or something that is going to make them feel better. I'm all for it. But on the other hand, it's kind of like, well, you are giving them a drug that you're lying to them about. I don't know. Where do the chips fall on this one? Yeah, that's a super important point. In clinical practice, of course not. So doctors prescribe drugs to people for their illnesses, and you won't find a doctor prescribing Smarties or Tic Tacs instead and not telling the patient about it. This is very unethical.

36:30These are all people who are in need of help and seek advice from a healthcare professional. In research, we have strict ethical guidelines as well about what we can and cannot do. Most importantly is that the benefits need to outweigh the risks for the participants. Especially when investigating nocebo effects, we have to be very careful because participants might have a strong negative feeling coming up in the experiment, and we of course want to avoid that, especially in pain studies. Yeah, I was going to ask exactly that. How do you even get people to sign up for these studies. If I had some chronic pain or whatever, I'm not sure that I'd sign up to literally get fake medicine.

37:07It would almost be insulting and maybe a waste of time. People, especially patients who are in pain or who have symptoms that they are in need of relief, are actually very keen on helping out researchers and promoting research. Otherwise, it's all about the incentive. So usually we pay participants a certain monetary compensation. And at least in my studies, they have the benefit of getting to see what their brain looks like from the inside. And then it's all about information. You tell them how long they will lie in the brain scanner, how many shocks or heat stimuli they will get. And you make sure that they know they can cancel the study at any point.

37:44Participant comfort really is my highest priority because my studies can be very long and taxing. But it also automatically leads to better data. and oh, I usually bring chocolate as a bribe. I mean, I prefer cash, but I know times are tough. When I was in college, they were offering, I remember this one study, they were offering$100 to sunburn one of your butt cheeks, just one. Sadly, I missed out on that one. But man, I don't know. It was tempting. 100 bucks back then, it's a lot of beer. I am glad your butt cheek is okay though. And since my studies are completely voluntary, that means only people who are interested in science or the money sign up.

38:23This is good on the one hand because the participant is motivated. On the other hand, the findings might not generalize to other people who wouldn't have signed up for such studies or who are generally not interested in participating. That's true. I can also imagine having one of your cheeks so sunburned that you can't even sit down. It's like, I'm not sure how much I love science after that. You know what's better than first degree burns on one of your butt cheeks? The deals on the fine products and services that support this show. We'll be right back. Once again, thank you for listening to and supporting the show.

38:54All the deals, discount codes, and ways to support this show are all in one searchable, clickable place, jordanharbinger.com slash deals. Now, for the rest of Skeptical Sunday. All right, so my curiosity, nearly satisfied for now, but can we systematically use these effects in medicine? Because from what you tell me, these are amazing. I mean, they're almost as powerful as that opioid painkiller in terms of the pain. it seems like we should do everything we can to harness these effects. Yeah, we can and we should, totally. I am 100 % with you on that. For example, 17 % of Germans, that is around 12 million people, suffer from long-lasting chronic pain.

39:33So more attention should be paid to the power of expectations in medicine than has previously been the case, just because it has been shown to help maximize the efficacy of medication and other treatments. In the future, doctors should definitely pay more attention to the previous experiences and expectations of their patients when selecting, for example, new treatments. The aim must really be for patients to start treatments with positive expectations and avoid negative ones. And if necessary, these expectations in the beginning could be raised with psychological support or a nice conversation with the doctor where people feel comfortable and like they have somebody who cares about them and who's going to help them in the end.

40:16It seems like it's all about setting people up in the right way. Yeah. Like you ever go to the doctor and they're just really cold and you feel like they're rushing you through there. It's a totally different experience than someone who's like, hey, so how are you doing? Oh, you know, this, that and the other thing. Oh, we're going to take care of you. Don't worry about that. You know, how the kids and you're just like, oh, wow, this person actually gives a crap. This is amazing. My back pain's already feeling better sitting on this bench in a gown that is open in the back with my butt hanging out.

40:42It's really incredible. And also, I always come back to my kids, you know, like my son was doing things like, oh, I feel sick. And I'd give him like a gummy, one gummy, which is like a vitamin C gummy. And I'd be like, this is the medicine for your belly. And he would take it every day. And he's like, oh, I'm all better now. And it doesn't just work on kids. I thought it worked well on toddlers, but I should start doing it to myself. Yeah, totally. And actually, as part of the research center where I work, we also collect anecdotal examples of placebo and nocebo effects from our patients and participants in the studies.

41:15And one striking kids example I have for you is a girl said that her dad always puts magic paper on her seatbelt when she's sitting in the car and they start driving somewhere. And that helps her to not feel nauseous and get sick. That's really good. I got to use that. My daughter loves to just projectile vomit after like three minutes in the car because she's looking out the window. There's so many use cases for this. As a parent, it's like I need just different colored gummies for every single ailment and I need to keep them in the central and center council of the car. Unbelievable. Yeah. And it's not only for the parents or the health care professionals.

41:49These findings are also of interest to the pharmaceutical industry where developing new approaches to treatment. And it also applies to active ingredients. the pharmaceutical form, dose of certain medications, or even the patient information leaflets that people get together with their medication. For example, positive patient expectations could reduce the required dose of a medication and therefore minimize the risk of side effects. The placebo effect can also accelerate healing after surgery, manual therapy, and psychological interventions. But how exactly it does this and under what conditions is still the focus of research.

42:26And I think we're going to be busy for quite a while just to find out everything we can about placebo and nocebo effects. I didn't think about lowering the effective dose, right? If somebody's taking like fentanyl for a back issue and they're having all kinds of side effects, or maybe it's developing a habit or they're relying on it or they can't function because they're always on this opioid painkiller. If you can get them to also have the placebo effect and you can cut the dose in half or down by, you know, a third, that's huge. I mean, that could literally save someone's life, especially if you're talking about a medication that's quite dangerous.

42:59So really cool. Yeah, that's totally true. There's even studies going on in our research center where people start off with 100 % of the real medication and then gradually this gets replaced by placebo so that it could go to a 50-50 % of drug and placebo in the end. And people might still be able to learn that the benefits stay and they won't need as much of the medication anymore because they can boost their drug effect with the little 50 % that they have with the placebo effect. Yeah, it's frankly, it's amazing. I really didn't know the placebo is this pronounced. Before we come to an end, though, I really, really don't want people to think that the placebo effect can cure their cancer or some other very real disease.

43:46So they don't need chemo anymore because they've got, you know, foot reflexology. I just, I really want to be careful with this because the effects of placebo are amazing, but they can't replace actual medical treatment. Yeah, that's a good point, Jordan. Thanks for bringing that up. I think it's good that we end the show with this with some realism. It's very important to clarify that the placebo effect also has limitations. Even though we try to systematically use it and study it, it cannot really replace gold standard therapies in many medical conditions. For example, cognitive behavioral therapy for people with depression or medication for cancer, like you said.

44:22On top of that, there are actual fake or sham treatments being deceptively sold to people, and those can do serious harm. In the case of homeopathy, this is not too bad. Best case, the placebo effect works really well to improve your health. But in the worst case, nothing happens and you just lost some money. Yeah, we did a whole skeptical Sunday about homeopathy. That was episode 882. 882. And it's like, yeah, hey, if you want to take this for a headache, fine. But if you're taking this for your pancreatic cancer, you're going to die. Yeah, I love that episode, by the way. But there are many expensive and harmful treatments out there.

44:55So I would, as a recommendation, double check each treatment suggestion and its source to make sure it is legit before you start buying or using it. For example, professional doctors will generally not shy away from explaining to you how a treatment works and why it is the best for you as a patient. It is important to close with the fact that the placebo effect is great, but it is not a magician or works 100 % all the time. And we definitely still need more research to find out which placebos work, for who, and in what situations. Spoken like a true scientist, you always got a hedge. Thank you so much for giving us an insight into placebo and nocebo effects today.

45:35So amazing. I stuff just blows my mind. I feel like I miss my calling. If I was a better student, I would have been a scientist. I definitely learned a lot. And I'm sure all the listeners did as well. And when we chatted prior to recording this episode, you actually told me that next to your research job, you do other forms of science communication, which makes sense because this was a really good episode. Tell us a little bit more about that, because I know people are interested in science. They might want to find out more about what you're doing. Yeah, of course. I'd love to. I actually have my own project called Science and Fiction, where I explain scientific research with fictional short stories.

46:09Do you like to read? Well, I have no choice. I read one or two books per week at this point. Me too. My favorite genre is science fiction with very dystopian endings, hence the name of the project. I started it during the pandemic, where I realized I not only enjoy reading, but also creative writing a lot. And I'm really passionate about explaining my research or other people's research to people who might have a bit of a harder time than me to read scientific papers that are endlessly long and really, really complicated. Yeah, I feel you. I read some of these studies sometimes just so, you know, if somebody makes a claim, I can maybe kind of check it.

46:44Yeah, they make me fall asleep a lot of the time. It's like needless complication. I feel like that's your colleagues love to complicate things needlessly and hedge. And it's like, OK, for God's sake. Yeah, I feel exactly the same. Researchers often use very complex language that not even other scientists understand. It's really frustrating. And my project, Science Fiction, hopefully solves that issue. It is meant as a space for people who like to learn about science, but also read science fiction at the same time. And I want it to be kind of like an open door into science and its results. Each contribution in my project includes a fictional short story, a scientific publication related to the story and the heart of it, which is an easy to understand summary of the publication and explanation of its connection to the story.

47:31So if I or somebody listening right now also likes writing, can we also contribute to the project? Definitely. I'm always looking for guest contributors. So just go to the project's website, scienceandfiction.net, and you can have a look. You'll find all the information you need about how you could contribute. Just as a little spoiler alert, there are also some stories about taking pills that will change your life forever and dogs behaving very weirdly. It's quite a cliffhanger. And thank you again. That's it for today. I'm going to go and try out that Tic Tac idea to get rid of the headache. And if my kids have eaten all the Tic Tacs, I guess I can just imagine taking pretend Tic Tacs for risks and side effects.

48:11Yeah. Ask your local scientist. Thank you so much, Helena. Thank you so much for having me on the show. If you're looking for another episode of the Jordan Harbinger show to check out, here's a trailer with Arthur Brooks. Anytime you catch yourself comparing yourself to others, you have to stop and say, that's what I'm doing. Don't do that. Oh God. Easier said than done. Yeah, I know. But although you've, once you know that the knowledge is power, I was just at a bachelor party and some of my friends were like, Oh man, some of our friends, they just became like high school teachers. And I was like, well, let me stop you right there.

48:40You know, happy those people are. They figured out what they wanted to do when they were like 24 They got married to somebody they'd been dating for a while. They had kids well before age 30. They're satisfied with what they're doing in a lot of ways. They have way more free time than you and I. We cannot sit back and judge. We're wired in a way that we're always dissatisfied. They're wired in a way where that is fine. I'm jealous of that on many levels. One in six Americans have actually stopped talking to a family member because of the election. That's pretty scary. It's almost one in five now.

49:09Yeah. Politics has become super, you know, hyper attenuated in our culture where it's taken on this outsized role and importance to assume ad hominem. This is what you're saying. It's like Jordan made this joke on Instagram. So therefore, I know it's residing in the depths of his heart. I bet you he bears animus towards some racial group. So wildly. But that's exactly what we're talking about. Motive attribution asymmetry on the basis of ad hominem. Don't be that guy. 93 % of us wish the country were more united. You're part of the problem when you do that. So I got a win-win-win proposition for our listeners and viewers today.

49:48Number one is I'm gonna make you more persuasive. I'm gonna make you happier. And I'm gonna start a social movement in your heart in a tiny little way to bring our country together. And that's answering hatred with love as much as you possibly can. For a great discussion on how we can bridge the divide in our relationships, our country, and even within our families, check out episode 211 with Arthur Brooks here on the Jordan Harbinger show.

50:37association with Podcast One. My team is Jen Harbinger, Jace Sanderson, Robert Fogerty, Ian Baird, and Gabriel Mizrahi. Our advice and opinions are our own, and I am a lawyer, but I am not your lawyer. Do your own research before implementing things you hear on this show. Also, we may get a few things wrong here and there, especially on Skeptical Sunday. If you think we really dropped the ball on something, please do let us know. We are usually pretty receptive to that. Y 'all know how to reach me, Jordan at jordanharbinger.com. Remember, we rise by lifting others. Share the show with those you love.

51:06And if you found the episode useful, please share it with somebody else who could use a good dose of the skepticism and knowledge we doled out today. I think there's a lot of really useful stuff here in this episode, especially for parents, as long as you're willing to lie to your kids like me. In the meantime, I hope you apply what you hear on the show so you can live what you learn. And we'll see you next time.