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Everybody, we're adding a special new feature to the podcast where you get to participate. I ask you to question of my guest. So here's what you're gonna do. Click on the link below and there you'll find the schedule of my upcoming podcast guests and you can see who's coming up. What the topics are and if you like to ask a question, just fill it out, fill out the form there, send that to us and I will read the question and your name on air and ask the question of our guest and we'll see what they come up with. So check it out, click on the link in the show notes. My guest today is Michael Bernstein. Here's his book, The No Sebo Effect, when words make you sick. Check it out. He is the experimental psychologist and I should say he's one of the editors, there's four editors here. We should give them proper credit. Michael Bernstein, my guest today. Charlotte, please. Cosimo, Locher, Locker, Locker. Cosimo Locker. Cosimo Locker and Walter Brown. All right, but let me give my guest the proper introduction here. He's an experimental psychologist and an assistant professor in the Department of Diagnostic Imaging at Brown University's Warren Alpert Medical School. His work is focused on harnessing the placebo effect to reduce opioid use among pain patients. Wow boy, that's a timely skill to have. He's director of the Medical Expectations Lab at Brown. Okay, we're going to have to dissect that Medical Expectations Lab. All right, we'll get into that in a minute. He's the co-author of the new book, The No Sebo Effect, when words make you sick along with the co-authors I already, co-editor's I already did. All right, Michael, nice to see you. I always like to ask my guest, you know, what's your story? How did you get into all this stuff? Yeah, thanks so much for having me. So I started with my interest in placebo and No Sebo effects in graduate school. I came about it in a little bit of an unusual way. I started doing research really on substance use and I was focusing in graduate school in particular on alcohol use. And for my, actually my master's thesis funny enough, I wanted to do a study to look at whether anxiety would increase how much alcohol people drink in a lab-based setting. But there was sort of a catch in that we didn't have any funds or frankly enough subjects who were 21 and over to participate in the study. So because of that, we recruited just any undergrad who were 18 plus and therefore we're not able to use real alcohol. So my advisor and I, we spent quite a bit of time brainstorming and we ended up doing it all with placebo alcohol. And very quickly the question of how do you make a convincing placebo alcoholic drink was much more interesting to me than the more substantive question that I started off with about anxiety. And so, you know, I sort of did that study it and that eventually launched me on to this path of looking at placebos and expectancies more generally. That's so amazing. I never thought about that. You mean just like non-alcoholic beer that that's not enough. You pick it up at the liquor store. Yeah, so not alcohol beer doesn't actually work as well and there were a lot of black protocols that were developed before my study. And those had to do with, you know, you see people pour flattened tonic water from real liquor bottles. You actually spray down the room with like a nasty smelling tequila. Like they're just like a bottom shelf alcohol. So as soon as you walk in, you get those smell cues and you know you do some other things. We did all of that and it still didn't work probably because most of the participants were underage. They knew it was illegal for us to give them alcohol. And what we did, which hadn't been done before, was we had a couple of confederates in all of the session. Well, excuse me, we had one confederate in all of the session. And the confederate, you know, sort of a long story, but they acted like they were getting a little bit drunk. They referred to their roommate who came home from this study last week and were pretty buzzed from it and some things like that. And with that, we were able to convince not everyone, but certainly the majority that they were at least getting a low dose of alcohol, you know, juries out. And if that would actually work for convincing people the high dose, you know, the higher the dose, the less compelling it's going to be. But it was a really fun project. And that was sort of my first exposure to doing placebo's placebo research. And it really fascinated me from the beginning. Yeah. So that's why I'm up here. Yeah, I wonder how much I'm just riffing here. How much of alcoholism is a kind of placebo, or at least perceived placebo by the user, in addition to the actual physiological changes in the buzz you get. And then the addiction to that buzz. But also then the perceived, I need this every day to kind of wind down from the dress of the day or, you know, feel good at in the evening or whatever it is, your thing is, would that be a kind of placebo? Yeah. So if the anxiety relief that you're experiencing, that's ultimately what causes the addiction is due to an expectancy effect rather than the pharmacological properties of the alcohol, then yeah, that would be a placebo. If I think that's what you were referring to. Yeah. Yeah. Yeah, that would be a placebo effect. And you know, they've done these studies, I mean, it dates back to like the 70s where they would give people real versus placebo alcohol and look at, you know, have different responses to stress and all kinds of all kinds of things aggression was one that was studying quite a bit. And you know, consistently you get a definitely get a placebo effect from alcohol, which is it's no surprise, because it, you know, alcohol, like so many of the other things that I'm sure we'll be talking about it has to do with responses on subjective symptoms, things like anxiety, things like depression, sexual arousal would be another one. And so all of that is does have a large placebo component to it. Yeah. So maybe we should start with a definition of placebo and then what a no-cibo is. Yeah. Yeah. And I think it actually makes the most sense to define them both at once. So both placebo and no-cibo have to do with the role of expectations. And so placebo effect is feeling better, having reduced symptoms due to the expectation of feeling better or having reduced symptoms. And a no-cibo effect is the opposite of that. So it would be, you know, having symptoms or feeling worse due to the expectation of that. So I think of them as like, they're pretty much opposite sides of the same coin. Right. So yeah, you talk about, for example, COVID-19, you open the book with that story, because I remember when I got the second jab, Moderna, the first jab did nothing. I mean, it felt great. So I, but now that I look back, I can't remember if I was expecting the second jab to dock me out or not and talk me on my butt because it did. And then I told everybody the story. Oh my God, the second jab was horrible. It was worse than I was horrible for all of them too, after that. Yeah, that's what I'm wondering now. Yeah, that's an interesting effect. But, but, but of course, you can't imagine placebo working on the virus itself, the SARS-CoV-2 virus. And yet it could still have physiological changes like I felt like crap, achy sore, you know, the runny nose and all the other stuff that went with it. How is it possible that just the expectation, if that was indeed the case, could cause physiological changes like that? Yeah, it's, you know, it's crazy. But our expectations, it's, it's amazing how much that they do govern. And, you know, some of the, I think, most interesting studies along these lines, you know, Ellen Langer at Harvard has been studying this stuff for a while. And so like as an example, she did one study where she basically, participants came into the lab and they were given like a very minor, you know, nothing serious, but like a very minor wound. And they, they had it so that some participants were in a condition with like a rigged clock. And the clock either went at half pace or double pace and then a control clock that went at the normal pace. So in other words, everyone thought I'm just picking numbers randomly here, but it gets the idea across. The study went on for let's say 30 minutes, some participants knew it was 30 minutes, but some thought it was an hour and others thought it was say 15 minutes. And then when they took pictures of the wound at the end of the study period, which again was in reality 30 minutes for everyone, those who thought more time had elapsed, like independent observers actually said that the wound from judging by images, objective images observed that the wound seemed to heal more so in that condition versus the others. So it's it's crazy how expectancies relates to all of these experiences, but absolutely. And it does govern, you know, exactly how this works is another question. And I don't think we know the answer to it, but it does seem to govern different kinds of physiological markers. Yeah, because pain is subjective, but it's real. I mean, there's actual signals. Oh, it's very real. Yeah. Yeah, why does it have to be so painful? This is one of these great evolutionary psychology questions. You know, why can't it just be like a red light that goes off that goes, don't do that again. Okay, I won't do that again. But don't make it miserable. Yeah, maybe it's the miserable that makes you really not do it again. Exactly. Yeah, you're really not going to touch that stove, you know, given just how painful it is. Yeah, yeah. But you know, like the what was it the gate theory of pain that like whatever is higher up from where the source spot is is blocking the pain from the source. Let's say you have a wound or something like your wrist is sore. And then you so I blend an athletic club, right? So guys are always icing icing their arms, the tennis guys. Right. So I've been reading stuff about ice. Does it really work? Well, my own doctor says if if it really worked, like if you really froze the tissues inside your muscles, this is what you call it when you go on to Everest and you get frostbite. Yeah, like frostbite, right? It's actual tissue damage. So it's not actually doing that. He, my doctor says that it's just blocking the signals from lower down. And so you perceive it in your head. Well, I'm feeling better now anyway, but everybody doesn't actually reduce the swelling. Correct. Yeah. Oh, that's interesting. I hadn't heard that before. Yeah. And there are papers to back him. I mean, he sent me, I said, Oh, come on, he sent me papers. But I've got other people to go, No, no, no, it really does reduce the temperature and the swelling, the inflammation a little bit. So I'm not actually sure what to think about that. Yeah, I haven't heard anything about that. But it does always surprise me how much these kinds of things crop up where different kinds of treatments that you sort of take for granted. And then it's like, Oh, actually, that that might be an expectancy effect there too. So it wouldn't, yeah, I guess it wouldn't completely shock me, but it does seem nonetheless, it does seem surprising because you hear all the time, you know, you've got to ice to reduce swelling. Yeah. Yeah. But so I guess it would depend then how deep it actually goes, the actual lowering of the temperature, you know, if it's deep inside, let's say it's your shoulder blade and it's, you know, in the arm socket there. And you know, that that's pretty thick. That's like a couple centimeters down in there. If I really lower the temperature that far down there, that would wouldn't that do tissue damage? This is the argument that they make. Huh? Yeah, I've never thought about that. Yeah. Yeah. Yeah. Yeah. Then the other thing, the other reason I wanted to have you on the show, because this expectation effect or whatever we deal a lot with with this, we deal a lot with alternative and so-called complementary medicine. Yeah. And you know, you know, people say, are you saying it never works? No, sometimes actually work. And my favorite study to sign on this is the one was a German study with acupuncture and migraine headaches. So and it was a pretty decent size and then they had three different groups. They had the the people that got the real acupuncture needles in the spots where they're supposed to be in the little orientation with the map and you follow the chakras and the energy points and all that stuff. Meridian's. Yeah. The meridians and all that stuff. And they and then then the second group got a faux needle effect where they they just put the needles in randomly or they just took the little the way it works is you have this tiny tiny little needle and there's a plastic sheath around all of them. And they put it like the sheath on there with the needle and they tap it. And so you can actually do that if the person's they're all blindfolded. And so it could feel like you've gotten the needle put in there, but you didn't. So they either did that or they just put the needles in randomly. And then the third group got no treatment at all. And so but the finding was interesting that the faux acupuncture treatment group had the same effect as the actual so-called real acupuncture effect. So it appears to have nothing to do with the meridians and the energy flow and the chi and all that stuff. But but what is it? You know, so I've long thought about this. You know, is it that you're getting touched, you're being treated, that you know, somebody is addressing your, you have a migraine, we're gonna do this and you're being touched, you know, being touched, we're human. We like to be touched. It's important. And so on. And maybe it's just that. Just the doing something that makes the difference. Yeah. So yeah, there's there's, you know, the doing something. I mean, just, you know, you're physically getting in a car, you're driving to an appointment, set a some preset time, especially if, you know, the acupuncture has maybe a soothing setting where they do their work. The other thing is interesting about acupuncture too is the needle. I mean, you have to wonder if like endorphins are released by the needle. And so there could be some kind of effect there even independent right where where it's done. Yeah, the acupuncture literature, and I don't know it extremely well, but it does seem to be a little bit mixed. Some studies seem to find an effect above placebo acupuncture. Others don't, you know, they've done things like you've mentioned of putting the needles in the sort of quote wrong spots as the control. They also have designs, needles that are retractable. So they're put in the right spot, but the needle doesn't actually pierce the skin. So there's different ways of doing these and I don't, the last time I dug deeply into it, I couldn't find a real consistent answer to is acupuncture effective above a placebo or not, which is very different from saying does acupuncture reduce symptoms because that seems to be the case that it does. It's just a question of what's causing that. The expectancy of factor, you know, something actually going on with with the needles and with where the needles go. Yeah. Same thing with meditation. Does it work? Well, in part, it depends on what you mean by work. Yes. Again, it's probably not going to cure. It's a cure of SARS-CoV-2 or AIDS or something like that. Yeah. But if it's reducing stress or headaches or pain or, I don't know, just the subjective ratings, you know, it's likely to have a huge effect. Yeah. Well, even the question, it's always funny when, because you hear this a lot, you know, well, does treatment X work? And, you know, you don't want to sound too academic. But when you really got to probe that, it's like, well, what do you mean by work exactly? Are you better after the treatment than before the treatment, in which case tons of treatments work? But that's still a very different question from does it work over and above and expect and see effect, which is the standard that we hold medication trials to and probably for good reason. But we aren't always consistent about that standard, I would say. Yeah. I remember when my wife and I went down to Deepak Chopra Center in Carlsbad, California for a long weekend. And he had conducted, he had been conducting studies on the effects of meditation. Again, it was a, you know, controlled things where you have the professional meditators, they're doing their thing. And then you have like amateurs that do it, you know, like once a week or whatever. And then you have people that they just show them right there that weekend. Here's how you do it. Here's your mantra that you chanted in your head and all that. And then people that just don't do anything. You know, but afterwards, of course, we felt great. You know, we're down at the beach side resort, this five star resort, you know, eating great food and green tea and meditation and massage and, you know, working out every day and the yoga and it's like, how could you not feel better? Yes. Well, in meditation too, is a tough one because how do you do placebo meditation? Right. And I know people have wrestled with that question, but it's obviously a very hard one. But deep, deep box belief is that those expectations actually do change your physiology. So for example, lowering stress hormones and that inflammation is one of the causes of disease, or at least how your body responds to a disease agents. And therefore, subjective things like what we're talking about here, have real world effects on real diseases, not just subjective pain, evaluation, say, but at least how your body responds to viruses and bacteria, say, or wounds or something or cancer or something like that. Interesting. Yeah, I know the meditation literature, it's people have been going pretty deep into what kind of effects you can have there. It's, yeah, it'll be interesting to see what comes up comes of all of that. Yeah, I think there needs to be a lot more research, but also what kind of meditation, because there's so many different types. And, and again, how, how often like once a day, 20 minutes, three days a week, you know, when you say does it work, well, we got to have those objective criteria by which we're measuring to say this is the effect here. You got to do it five days a week, 20 minutes a day, minimum, you know, sort of like exercise, you know, the doctors try to come up with standards, you know, exercise 20 minutes a day, five days a week, something like that, which I don't think is enough. But, but, you know, ideally you get it. Ideally you get at those, those response relationship, the more you do it, the better you feel. Yeah. Yeah. Okay. So, um, the no SIBO then would just be negative thoughts or expectations. The pain is going to be really bad. Like I'm going to prick you with this needle now to give you your vaccine or whatever. I really can. Like when I have to give blood, I cannot look. And it, and it, you know, if I compare it to other forms of pain I've had, it's nothing. Getting, you know, a needle jab to draw blood is nothing, but it's still, you know, I can't look. I just like grit my teeth. I mean, I've been in some bike crashes. You would not believe how painful it is. I mean, the description we give is that get your car up to 30 miles an hour. You're just wearing a lycra like your workout shorts and shirt, and then open the door and throw yourself out on the pavement and just get in. Yeah. Yeah. I mean, this would make you a thousand times worse than blood. And yet for me, you know, you have a bike crash now and whatever, finish the ride, take a shower. I'll be fine. And yet the needle thing is even more, you know, that's what you're talking about. That's that those expectations. Yeah. Well, and also like, I mean, just compare, because it's funny. I'm the same way too. I, I have a really hard time with needles, but when you actually compare just the raw physical sensation, I mean, stubbing your toe is a lot worse than getting a needle. We're stepping on a Lego block. Yeah. Yeah. That's way more painful. But you also don't know that that's coming. Whereas with a needle, like, you know, there's again, like going back to the ritual, I mean, there's a whole ritual surrounding and you go into the doctor's office, they wipe off that area of your skin and you know, like exactly when that needle is coming. So you have, you have the expectations of what's going to happen, but then you sort of have the whole ritual surrounding everything just prior to the needle as well. What do we know about negative expectations like hexes or, you know, the number four is cursed. Did your culture 13 or whatever that was or, or people are more likely to die on this day than that day because in that culture, this is a bad day or something like that. Is there any truth to that or are those urban legends? Oh, there's a shocking amount of truth to that. So the, the number four, what I think you're referring to is that in, I believe it's Chinese and Japanese culture, the number four is considered unlucky. And then they looked at, and this is not study for me, others have looked at deaths according to each day of the month and find that when you, when they break it down for white Americans, it's pretty much flat from, you know, day one to day 30 or day 31. But among Japanese and Chinese Americans, you see a really big spike on the fourth day of the month. So it does become seemingly this type of self-fulfilling prophecy. And that's one of the cool things I would say about this research is these cross-cultural manifestations of it, because it does seem to, to crop up in those ways. And like similarly, and I think, I think this is Chinese culture, you know, there's, according to things, I'm not totally familiar with exactly the exact mechanism, but like, there's beliefs that like certain times of the year, it's unlucky to be born. And it so happens that for people who hold those beliefs, folks that are born at that time, have a shorter life expectancy than those who are not born at that time, or compared to people who aren't from that culture and don't hold those beliefs. So it really does seem to be some truth to it. Right. Yeah. That's just so weird because a cause of death, I mean, medically speaking, there should be something, you know, blocked arteries and led to a heart attack, you know, the stroke in the brain, or you know, something killed him. Yeah. Yeah. And I don't know, maybe in that culture, the kid, the doctor can write down, you know, died of fear of number four or whatever. But what's actually going on? I mean, you know, it's just a keel over dead just because you think you are. Yeah. And obviously you can't really answer that with the epidemiological studies, you know, I don't think we know what's going on exactly. I would venture to guess like, you know, if you think that four is in really unlucky number, I don't know. I mean, if you're maybe at the end of your life, and you know, it's the fourth day, fourth day of the month, maybe you behave in different ways than you would for the third day or the fifth day, somehow you're more resigned, or who knows what it could be. But yeah, like when spouses die, you know, long, long married spouses die within days of each other. It's like, whoa. Yeah. I mean, well, maybe it was just something keeping them going. And then then the natural deterioration happens after that. It's hard to say. Exactly. And let me read this part portion from your book. I marked different pages I wanted to ask about. So here you're talking about adverse drug reactions, which I think is super important because of the amount of money. Drug related morbidity and mortality costs the United States over $500 billion in 2016. Whoa. One such causes labeled adverse drug reactions, ADR, which is a fancy way of saying drug side effects. A study from England found that over a six year period, more than half a million people were admitted to a hospital with an ADR. This means that for every 1000 people who went to the hospital, 15 were there because of an adverse drug reaction. Whoa. But they were sick only from the, but were they sick only from the chemical ingredient of the drug? Or was their illness due in part to the no sebo effect? All right. Go ahead and riff on that, if you will. Yeah, sure. So, you know, that gets at probably the easiest to understand cause or, yeah, the cause of the no sebo effect, which is the side effects from medication. And so going back to that COVID example, I think that's a good one to jump off at. When you compare side effects for people that are in, that were in the placebo arm versus the real vaccine arm of those trials, what you see is that around in the first shot, it was 75% and in the second shot, it was 50% of the side effects that people experienced in the real vaccine arm were also in the placebo vaccine arm. So you have a case where a lot of the times side effects that people attribute to some type of medication could be due to expectancy effects. And some of the things where that really seems to come up with is like statin medication as one example. In one study that is often talked about when it comes to the no sebo effect, really, really nifty design. They gave patients and, interestingly enough, these were patients who had previously been on a statin but had discontinued the statins due to side effects. Nonetheless, they got them to be willing to go back on statins for the study. And in one month, they, in one month, let's see if I can get this right here, one month, they took statins, in one month, they took placebo. And for both of those, they did not know which one they were getting. So it was like double blind for each of these months. And then in one month, they took nothing as a no treatment control group. And what you found, what they found is that side effects were about double for both the placebo and the statin month or portion of the study compared to the no treatment portion of the study. But there was very little, I mean, it was really negligible, very little difference between placebo arm and the drug arm. And once again, these are people who had actually gotten off statins because they couldn't tolerate the side effects. And yet it ended up being that 94% of the side effects that they experienced were due to the placebo response. And there, I think it's also important to distinguish what I mean by no-cibo response versus no-cibo effect. So no-cibo response refers to symptoms that you experience. And this could be due to those negative expectations. And that would be the no-cibo effect. But it can also just be due to the fact that in day-to-day life, people have symptoms from time to time. It's going to have to do with just the passage of time, regression to the mean, all sorts of other things like that. Right. Yeah, I took statins for a while. My cholesterol is always on the margin. And every doctor will tell you, just take them. Okay. And I did have some of the side effects. Not terrible, but some of the kind of jumpy leg at night, a little cramping on long bike rides occasionally. And then I tore my Achilles playing tennis. And one of the first things somebody asked me, "Are you taking statins?" One of the older guys, I'm like, "Uh, yeah." He goes, "Aha." I went, "Oh, come on. This has got to be one of those bullshit things." And I really don't know what to think about. I've read a bunch of stuff. And my doctor, he explained he's not a huge fan of statins. He's not one of the automatic, everybody should take it like water, guys. If you've already had a cardio incident, then probably the statins are going to work. But if you've never had any issues and you exercise and eat well, and so on, probably the effects are going to be harder to see statistically in groups. Anyway, so I don't know if you've read about statins beyond the no-seebo effect, but I'm not sure what to think on that. Yeah, I've only really looked at it in the context of no-seebo. Yeah, not so sure. Do you not get any medical advice? No, definitely not. Yeah. Hey Amazon Prime members, why pay more for groceries when you can save big on thousands of items at Amazon Fresh? Shop Prime exclusive deals and save up to 50% on weekly grocery favorites. Plus save 10% on Amazon brands, like our new brand Amazon Saver, 365 by Whole Foods Market, a plenty and more. Come back for new deals rotating every week. Don't miss out on savings. Shop Prime exclusive deals at Amazon Fresh. Select varieties. Now, okay, so then you also cite the meta-analysis here, big reports synthesized a bunch of smaller studies in this meta-analysis authors looked at 33 earlier studies of the frequency of ADRs in primary care. About half of the studies are based in Europe, the other half in the United States and Australia. In total, the rate of ADRs varied widely from less than 1% to 65%. Right there, I'm like, "Huh, that's a huge variance. This is precisely why a meta-analysis can be so valuable since any one study is liable to over or underestimate the true range." On average, across all 33 trials, the researchers found a prevalence rate of 8.3% for every 100 patients in primary care ate experience and adverse drug reaction. While this may seem like a small proportion in the United States alone and typically more than 400 million primary care visits a year, 8% translates to 32 million ADRs. Well, that's a lot, and they have to be traded. I love this quote you have from Sir William Osler, who you call the father of modern medicine. I've never heard of that and never heard that description, but that's interesting. He says, "The person who takes the medicine must recover twice, once from the disease and once from the medicine." Is that really true across the board? Is that what he meant? All medicines? Yeah, I mean, I'm sure he was being tongue-in-cheek with that. But the point is, it's very interesting when you see these tidbits historically from people that the word no seabode didn't come out until the '60s, but there were people who seemed to sort of understand the concept that long predated it. That's why that quote was in there. Yeah, interesting. Just some other sections here. According to anecdotal reports, this man who's being treated for depression swallowed an entire bottle of medication in a suicide attempt after his girlfriend dumped him. Realizing he wanted to live, the young man immediately admitted himself to a hospital where we are told. Previously ill, he lingered near death. He couldn't breathe. His blood pressure was dangerously low. Doctors then realized the man had been a participant in a study for a new antidepressant, but he hadn't been allocated to the placebo, but he'd been allocated to the placebo arm. It was not the poisons of a drug that led to his near lethal illness. It was the journalist claimed the nocebo effect. Convency was dying. He was actually beginning to die, and then you continue, or whoever your author is here of this particular chapter. Undoubtedly, yes. Undoubtedly, these episodes make for compelling column inches and sensational stories as the journalist say if it bleeds, it leads, nor are such scoops. Holy new, voodoo death has also been attributed to nocebo effect. The term was coined by physician Walter Cannon in 1942 to refer to cases in which people died within days of local traditional healers placing ritual curses on them. Yes. I'm glad you said what you did a second ago, because I think I'll give this disclaimer once, then I won't give it again. I'm an editor of the book. What you just read was a chapter written by an author, not me. I think that one was probably Charlotte Gleese's chapter. Yes, correct. Yeah. Yeah. The voodoo death and that story of the anti-depressants, that is just really fascinating. It's only a case report, but it was someone who was trying to commit suicide, and they were enrolled in a study, an anti-depressant study, and so they swallowed, I think it was like 20 pills, or 20 to 30 pills somewhere in that neighborhood, and then they ended up in the ER, and they were really very ill. And then, like you said later, it was found that they were actually in the placebo arm, not the drug arm. Yeah. Yeah. Again, you talk about Walter Henry Beecher. I think that this is from your introduction here, who served as a physician in World War II published a series of seminal papers on placebo effect. Beecher documented instances where he gave wounded soldiers saline at his saltwater, but told them they were receiving a powerful pain killer. Beecher did not engage in this deception of cruelty. It was just the opposite. He was an anesthesiologist, and he didn't have enough morphine to go around, but he noticed on the battlefield that sparked 70 years of modern day signs. The placebo effect soldiers experienced substantial pain relief from the saline. Again, how is that possible? I mean, if you're wounded, you're lying there, your arm is blown off or whatever it is. I mean, it's got to be truly painful. How is it? Yeah. How is it possible? Yeah. So I think that goes to this question of, well, what conditions do placebos work for? And what you really see is that it works for conditions that are inherently subjective, and pain is right up there. It's either pain or maybe depression. Like those are the ones where we have the strongest evidence for these placebo effects. So yeah, that is a story that's really interesting, and that's sort of what sparked the whole much of at least the study of placebos was Henry Beecher doing exactly what you just read about. And you can understand why. There wasn't much morphine to go around. He wanted to do something, and so that your saline was better than nothing. You can certainly see it. Yeah. So transitions to the ethics of this. I guess it's a form of deception, but is it a noble lie in that sense? Or could we reasonably argue that there's so much we don't know medically about pain and how the body recovers and why some people recover and others don't. Why not just say this may work? And maybe it will, and that's okay. Yeah, well, I'm not sure if there would be, if I understand you correctly, I'm not sure if there would be deception there. I think the deception would come from misleading someone, you know, like in that story of Beecher, you know, he would mislead people into thinking that they were getting morphine. But what it does is it really forces you to reconcile with the two different values that in this manner come into conflict with each other, which is improving patients' well-being as much as you can and being honest with patients. And so this pose with the question of, well, what do you do when you can make the thing you can do to make patients the best is by not being honest with them? And, you know, here in the US, we would, you know, certainly lean on the side of being transparent and sort of saying honesty is more important than helping patients reduce their symptoms. But that hasn't always been the case, and not every culture thinks that way. So you do see these competing values, or I should say these values that you wouldn't think would be in competition with each other. But placebo's can be quite interesting because it does show how they are in conflict at times. Yeah, I guess the ethical question comes down to what you mean by a lie or deception. Again, my point is that if there's so much we don't know about how the body works and, you know, what, you could say statistically, you know, you have a thousand people and they all get this particular kind of cancer. 40% will survive five years out or whatever it is. You can't point to one of the thousand and go, that guy is going to die in this particular time. All you can say is statistically, and the unexplained variance there kind of opens the door up to say, look, we don't actually know what the treatment is. This might work. That might work. Try this. And maybe you need to pitch it a little hard. Like, let's try this. This may work. In other words, I don't want to call it lying, right? Well, what's this in that example? Try this, whatever it is, the saline solution, maybe not the saline solution. But, you know, like, you know, for different kinds of cancers, there's the standard treatments. And then, and then there's a bunch of alternatives. You know, you just turn to the alternative complementary medicine literature and there's tons of stuff you could try. Probably most of them don't do anything, but maybe they do. Maybe don't do anything above a placebo. Yes, above placebo. But maybe that in itself is has value. And yeah, I don't know. Yeah. So I can riff on that for a minute, if you want. You know, so let me go back to no SIBO for a second. So one of the things that's been talked about says like what, you know, patients or providers can do is something called authorized concealment. So this would be like you go into your doctor, they're prescribing you some new drug, and the doctor says to the patient like, look, I can tell you about the side effects of this medication, but just me doing that is going to make it more likely for you experienced those side effects. So if you would like, I can tell you about the ones that would be really concerning and require medical attention, but not tell you about the other ones. And you sort of get the patient's consent for that. And so that's been proposed by researchers in this area. And I think it's something that really ought to be tested more than it has been. It's been answered a little bit, but not much. You know, but it makes me wonder if you could do something similar with the placebo effect. So like, you know, you could maybe have on certain intake forms. I'm just thinking off the cuff here. Like, could you ask patients ahead of time, you know, explain to them a little bit about what the placebo effect is and say, you know, if there were an opportunity where I thought that you could improve due to the placebo effect, would you like me to take advantage of that or not? And that, I think, yeah, you know, that that feels like it gets at this issue of honesty, because you're, you know, the patient is consenting ahead of time. So there, it's not exactly that option, or at least they're, they're agreeing to be deceived, which in a way means that they're not being deceived in the first place. Right. Yeah. I mean, my sympathies go out to a lot of these doctors who are pressed to do something, anything. Yes. And they don't know what to do, because it's hard. It's hard. I remember, you know, I was a caretaker for my stepfather for several years. It was in his mid 80s and, you know, just aches and pains and, you know, everything starts going wrong at that age. And so I would take him to various doctor's appointments and, you know, can you give me something that I just feel like crap or I'm in pain or low energy, whatever it is. And you could see the doctor, doctor struggling like, okay, I want to help this guy. And here, try this and give him a script, you know, they give me something I can take, you know, and who knows what works, you know, and, and it wasn't clear what, what the problem was. That was the other thing. It was, you know, sort of a Parkinson's like or pre Parkinson's or maybe these little tiny strokes in that are not obvious. And it could be causing causing this tremor or this uncomfortableness or whatever. They really, really couldn't tell. And I think a lot of medicine works like that. It's really more art than science. And so there, there, the placebo is, you know, why not? Here's, try this. Yep. Yeah, it's funny you mentioned that. So some colleagues and I did a study a number of years ago where we interview primary care providers about placebo effects and, you know, their experiences with it. And it was really surprising how, to me at least, how forthcoming they were. We had, you know, Harvard trained physicians sort of talking about how they, and actually if it was Harvard trained, but they were associated with the, the Harvard hospitals, you know, that they use placebos in their, in their practice. And, you know, they knew what they were doing. And I don't think they were happy about it. But I just was kind of blown away. And see, I actually have a couple of quotes here in front of me. Yeah. Let's see. So, you know, you know, one of them, for example, as Dr. said, a lot of times we check vitamin D. If it's low, you're like, I don't know, maybe I'll just prescribe it. It's probably not harmful, probably good for them, but unclear if that's helping whatever symptoms. And so, right along, walking to what you're saying, you know, you can have sympathy for these doctors, but yeah, I think a lot of what they do probably is largely placebo. And I think to a certain degree, many of these doctors kind of understand that. Yeah, well, that's how we got in the opioid crisis in the first place is when the measure of subjective pain became one of the commonly asked or tested criteria that doctors use, blood pressure and your weight and all this stuff. And, you know, what's your subjective rating and pain on scale one to 10? Where are you today? You know, how do I know that your seven is my seven, right? It's the problem of other minds. I don't. But I guess it's a way of setting some benchmark where you can say, okay, you're an eight today. Now, let's try this, whatever the this is. And, you know, tell me next week how you feel or tomorrow or an hour from now. Well, I'm a five. Okay. Well, that's good, I think, right? I mean, that is better than an eight. It's better than an eight. I get the justification. I mean, the Sackler family and Purdue pharmaceutical, they got what they had come into them because they definitely knew it was addictive long before they did anything about it because the profits were so huge. No question about it. And, and their RFKJ makes a good point about the regulatory capture by big pharma. That does happen. You know, that was unfortunate. But there are a lot of people that are suffering with chronic pain. And, you know, they have a hard time functioning, keeping their jobs and their families and so on. And, you know, we don't, we have an obligation to do something for them and the pain killers work. But, but as as you point out in the book, that, but they all have side effects like addiction. Yeah, that's a big one. So tell me about your, your research on, on the opioid crisis and all that. Oh, sure. So I'm just actually just kind of wrapping up a study here. We haven't analyzed it yet. So I've been getting into this field of open label placebos. I don't know if that's something that you're familiar with. No go. Yeah. What is it? So it refers to placebos that are honestly described as placebos. So it completely takes away the deception element. So like if you were in a study, it would be, you know, Michael, take these pills, actually got some here on my desk, you know, comes in a bottle and it says placebo right on there. And so there's no deception at all. And, you know, there have been a number of trials now where they give these placebos to people, all different kinds of conditions. Again, the patient knows that they're taking placebos and they still experience relief. There are certain methodological questions, you know, around like, well, how do you, what's the control group for that? And I think those are important things to think about. But putting that aside, you at least get people to do better on those honest placebos versus not on the honest placebos. And so the study that I've been working on now, which we're just wrapping up, I've been ongoing for two to three years at this point, is that we took patients from the emergency room here in Rhode Island. And if they were being discharged with opioids, we randomized them to either get these honest placebos or not, the not being the treatment as usual group. That's just they walk out with opioids or whatever else just as, you know, anyone would leaving the ED. And what we want to do is see if the open placebos can reduce how many opioids they ultimately take. And so hopefully I can have an answer for you in a few months on whether that was actually effective. But you know, if the bottle says this is placebo, I guess the question is what in people's minds do they read that to mean? Because if the placebo effect is real, which it appears to be, you can't say this bottle contains inert objects that do nothing, and it will have no effect on you. Because because the placebo effect is the opposite of that, it may be inert, but it could have a big effect on you. Yeah. Yeah. So what it is in these studies, and including the one that I've been doing, is that you explain to them about the placebo effects. And so you do, you know, it is tricky, because you do give them positive expectancies. It's not just like, here's nothing I want you to take it. It's, you know, here's a placebo, placebo means that, you know, it's like a sugar pill, there's no real medicine inside of it. However, the placebo effect is very powerful, and it's been, you know, study a lot by researchers over the years, people watch a video about the placebo effect. And that's one of these, what I was talking about with it being kind of methodologically tricky, is like, well, when you get an effect here, what are you exactly getting an effect of? It's sort of some combination of the placebo itself, plus the description of what that placebo is. Yeah. And so it does put in expectancies. In the case of the study I'm doing, there's also a conditioning element to it. So what we're having people do, we'll see if they are actually going to be adherent to it, is every time they take an opioid pill, they're asked to take a placebo as well. So let's say they walk out of the ER, they get a bottle of whatever 10 like it in or 10 percocet, you know, if they're taking, say, seven of them, then that means that for seven times, they're taking an opioid and a placebo. And just that sort of, you know, classical conditioning, that repeated pairing, we're hoping will enhance the placebo effect. And there is some evidence of this from the placebo literature. And then they're given the option of taking placebo's not paired with an opioid. And so that might be a way of sort of extending that pain relief. Interesting. I don't know if that will work, I mean, I've taken hydrocodin or I've had two hip replacements, so they give me the big bottle of hydrocodin. And I really like it, man, it's great. Yes. Yes. I mean, I manage, I work out the morning and I would take one or two of these things and I'd come to work here and write. And man, I was really creative and energized. I get right all afternoon feeling good, happy all evening. And then they ran out and I'm like, hey, doc, and he goes, no, no, no. This is long goes that. Well, the second was 2018. So after the crisis, the first one actually was 2013, and I was able to get more hydrocodin. Oh, I bet. Yeah. And I don't think I actually have the addictive person. I don't think I would get addicted. I think, you know, not everybody does. Some people could take, take them and not get addicted. I think I'm one of those. But even trying to convince the doctors in 2018 that I'm one of the non addictive, no, no, no, you're not getting anymore. And so if you. That's exactly what everyone would say. Yeah, exactly what the addict would say. Yeah. And it's true, I would not want to risk it. I suppose, because the effects of people's lives are horrible from death to losing their jobs and families and so on. Pretty bad. But I would like to think that the placebo wouldn't work. I would notice. But maybe not. I can't honestly say now. Yeah. And it's also, you know, it isn't like an on off either works or it doesn't. I mean, you can have these cases of it working, though, not to the full effect of something like an opioid medication. So yeah, it really should be thought of as existing on a continuum rather than a dichotomy. Yeah. I mean, really, medicine's not it's old as a profession. But you know, I'm told by medical historians that it really wasn't until pretty far into the 20th century where it was better to not go to the doctor than go. I believe it. Yeah. Just, you know, all the sudden, again, all the side effects and all the stuff that didn't you before, some of ice, no, and washing, things like that, just basic stuff. Anesthesiology doesn't really come online until late 19th century and really refine where they could really control it until early 20th century. Wow. Yeah, it's just staggering. And from a research standpoint, you know, the idea of double blind placebo controlled study, I mean, that was, I mean, there's some very early kinds of reports, you know, you might talk about what some of those looked like. But by and large, it didn't really start to happen at all until like the 1930s and then it wasn't until a couple decades later where people were doing it more regularly. So like the methodology that we take for granted as figuring out what kind of treatment works, you know, works again in air quotes, by which I mean, it works above placebo effect. Like that methodology is actually amazingly new. I know. It's like this we're the middle of the revolution. You know, yeah. And that's to say nothing of like, you know, the FDA's requirement to show two, two trials that are effective. And then, of course, it opens up the problem with the file drawer, you know, right? Lots of trials that are not effective and just, you know, push it off to the side and not really talk about it much. But yeah, you know, it's from from that perspective, you can almost ask the question of like, well, why would you expect medicine to work very well before there is even a methodology that we would accept as being useful to study that question. Right. Yeah, it's like determining causality in science is a lot harder than most people realize, which is why we all these tools, you know, you don't know if it's one of the confounders that you're just not even thinking about. And you think you're studying X, but you're actually measuring Y. And you don't even know that that's what you're doing. So you have to have all these other factors in there and control for those things, which is why I like the comparison method for like longevity, for example, I've had a bunch of the longevity people on the show here. You know, how do you know it's this particular thing and not this other thing that it's, you know, exercise or it's not smoking or it's having lots of friends or, you know, this, you know, there's like a dozen different factors that seem to make a difference. You know, and a lot of it comes from what we just do, because you can't control people. You're in the control group, so you can have any friends for the next year. Yes. But you could know no salads for you for 30 years. Yeah. Yeah. But you can after the fact, look at what people actually did. But here again, then well, what they said they did, you know, they're it's all self report. You know, I never eat junk food. And then, you know, the spouse goes, actually, he has McDonald's once a week. Oh, okay. Yeah. So I mean, there's yeah, right. So there's a self report issue, but then there's also just the, I would say the more fundamental problem of some things you can't do experiments on. Yeah. And yeah, that is interesting to me, those kinds of health studies, because it's, you know, it feels like it's such a messy field. Like, you know, we don't, I mean, how long ago was it when like, you know, fat was really terrible for you. Unbelievable. I know. I know the whole pyramid, food pyramid has been flipped upside down just the last time. Yeah. And I wonder how much of that, you know, I don't know in penetration science. But you know, I just wonder how much of that is due to the fact that we really, I assume can't do experiments in these things. So we have to do. Yeah. Well, there's some with prisoners. Yes. You know, they're not going anywhere. Yep. Yep. And they're going to eat what we give them to eat. Right. But even there, the critics have pointed out that the prison population that's in your end is not all the same people. Some people get out, new prisoners come in, they have different, you know, backgrounds on what they were eating and so on. And even that's not for sure. And I would assume that now it's probably very hard to get that kind of research approved. Yeah. Yeah. Yeah. Yeah. For sure. Yeah. So answering new questions, I don't know if feasible that way. So you look at the blue zones, you know, these are the places where people live a long time, like in some island in Crete, I think, in a few other places around the world. So then, well, what did those people do for their lives to live so long against just an odd average? They had this many friends, they walk every day, they keep journals, you know, they eat a Mediterranean diet that's fairly balanced, they don't drink a lot, they don't smoke, you know, pretty much you can just add it up and get maybe 10 things you could do. But even there, it's kept, we deal a lot with the singularity people, you know, we're going to live forever. It's like, okay, good. And I hope you're right. I'm for it, but, you know, isn't in fact the case. And they, well, you know, there's this one study that shows the extract of seaweed or whatever, you know, may make a 1% difference, you know, it's like, yeah, you know, but it's diminishing returns, right? Like, here's the 10 things you could do, you know, don't smoke, drink a moderation, have friends, you know, work out and, you know, so on and so forth. And that gets you like 90% of the way there and everything else, you know, maybe 1% here and 1% that maybe, you know, but you look at the studies, you know, an of six, you know, sub tiny little thing is like, I don't know. Yeah, yeah, it's amazing to see how much those dietary, you know, guidelines and all of that have shifted and how much it seems like we don't yet know about it. I think that's the case. Well, I think aging for the most part is multi-factorial and it just happens across the board in all systems at the same time, roughly in your mid to late 80s. I'm curious now, these the singularity folks, is that due to AI or is that something different? Yeah, no, it's a AI. These are the AI people, yeah, like Ray Kurzweil, but others. And also sometimes called transhumanists or the extropians, they're against entropy. I find it all, I find it super interesting compelling, almost like a religious faith, but faith and technology and science, which I like. And you know, maybe they're right. We're the generation that will live forever. And the argument is what's called longevity, escape velocity. So, you know, this idea that people are living longer, you know, every year, every year you live, on average population lives like a week longer than the previous year or something like that. Or maybe it's a month longer. At some point, if you follow the kind of equivalent of Moore's Law curve going up, if you can live a year longer for every year that you live, you reach escape velocity and you get to live. This is the argument. Right. And now I'd have to apply to it every potential age that one could live as well. Yes. Yes. Right. And I don't think it does. In any case, I think it's again, that diminishing returns. It's just more of us getting up to the upper ceiling, which is about 115, it appears. And, you know, there's more and more centenarians than there's ever been. But, you know, no one's making it to 150 now, not even close, you know, because of all the other things that go wrong. Anyway, I'm for it. I'm not against it, you know, but when people ask me this, you know, don't you want to live to be a thousand? I just say, get me to 90 without Alzheimer's. Can you do that? It's like, uh, well, no, we can't do that. It's like, okay, just solve that one thing right there, Alzheimer's dimension. That's on those extra 900 and then we'll deal with the next 900 after that, right? Yeah. You know, and, uh, you know, that's the, that's the problem. So, I mean, again, the plus even no sebo stuff. I mean, it can only take it so far. There's just physical limitations to what, what we can do, I think. Yeah. You know, you're not going to use expectancies to cure every kind of ailment. It really has to do with those things that are, are subjective, that are governed by the mind. However, exactly, you want to think about it. Psychosomatic would be another phrase that's used a lot here. Yeah. Well, but again, it's quality of life. You point out towards at the end of your book here that, uh, you know, health and vitality and well-being are critical. I mean, that's, you know, don't worry about, the number of years. I always tell these guys, don't forget to enjoy it today. You're actually alive and young and strong and feeling good now. Don't, don't, don't miss out on that. Right. Uh, you know, so to whatever extent these things work, you know, even if it's just subjective well-being, but it's all subjective well-being. I know the, the happiness literature pretty well. It's all subjective well-being. It's just, you just ask people, you know, how happy are you? This is not subjective. Yeah. Well, there are some objective criteria I'd like to have. Like, I'd like to fly private. So other than that, I don't really care about the mind. Okay. I wanted to bring up another thing here book you talk about, uh, Franz Mesmer, the 18th century German physician who developed an interesting cure for a range of maladies. Mesmer believed that illness could be alleviated by using magnets to govern the flow of fluid in people's bodies. This might seem preposterous, but bear in mind that Mesmer lacked any of our modern day tools of science and medicine. He lived in an era when leeches used for bloodletting were considered therapeutic. Nonetheless, King Louis the 16th king of France at the time was skeptical of Mesmer's claims. He established a commission to investigate led by Benjamin Franklin. Franklin and the others did what we would now refer to as placebo controlled studies who has. After investing billions to light up our network, T-Mobile is America's largest 5G network. Plus, right now, you can switch, keep your phone and we'll pay it off up to $800. See how you can save on every plan versus Verizon and AT&T at tmobile.com/keep and switch. Up to four lines via virtual prepaid guard, a left 15 days, qualified unlocked device credit service, ported 90 plus days with device ineligible carrier and timely redemption required. Card has no cash access and expires in six months. As the commission put it, separate the effects of the imagination from those attributed to magnetism. The commissioners led patients to believe they were being magnetized even though they weren't. But all the usual magnetism side effects were still present. On one occasion, the commission noted that after a minute, a patient began shivering, convulsing with chattering of her teeth, twisting of her arms and trembling of the whole body. It's no surprise then that they ultimately concluded the results attributed to Mesmer's treatment were due only to the imagination or the expectation effect there. So anyway, I was going to point out how we pointed this out to you before we started recording. But we actually published that report from Benjamin Franklin and Lavoisier in skeptic. Here it is in 1996, volume four, number three. I have cases of them right over there. If you want to order this one, this is what the kind of militia cover issue there in which and here's and here's the original French cover of the report in our English version of it, testing the claims of Mesmerism. I love the study and I love that you mentioned that because it was really, I think the first attempt at a controlled placebo control effect by magnetizing some and not magnetizing others, but telling them they were magnetized and to see what the effects were. It's so good. Yeah, it's really interesting to read that report because they go through just like, it's sort of thinking of it as like one case study after another as kind of how Benjamin Franklin and the other commissioners wrote about it. But they're thinking right along the lines of how we think now about placebo effects and doing blinding the double blind methodology or at least single blind the patient wouldn't know. And it's just kind of cool to see how they call it imagination. Now we would call it expectation, but probably it's referring to the exact same phenomenon. And it's something, you can sort of lose sight of it when reading it, but it's like Mesmerism was a very common treatment. So I mean, this was debunking what in that era was like, you know, something that a lot of people got it wasn't fringe, you know, to the point where the King of France actually wanted it to get studied. That's what led to Benjamin Franklin doing the report. Yeah, it's amazing. Our translation of it and publishing of the whole thing was 14 pages long. And it's pretty dense. It's 40 pages in our page. It's pretty dense. It's pretty long. But it's like a, you know, a relief awful long journal article in which there's even little riffs in the margins margin, which I guess it's almost like a little abstract or subhead for what's in the section, like experiment eight, eighth experiment that gives the same result, a woman believing she is magnetized as a crisis, ninth experiment, giving the same result, a woman who believes she's being magnetized through a door as a crisis. They also did trees. They magnetized trees. You know, people would like sit there and hug the tree. Okay. It's magnetized. It's been a little while since I since I read it, but I think they also did the opposite of exposing some people to the magnet without them being aware of it. I think they hide it behind certain areas. Exactly. Right. Right. Right. Yeah. Another control, right? Just in case it really, right? Magnetism really does work. I mean, magnets do something. Although they're pretty weak. I mean, the magnet on your refrigerator is stronger than gravity because it holds itself to the to the fridge. But if you're more than like a mill, a couple millimeters away, ineffective, let's see 11th experiment, same result with a cup. They magnetized a metal cup 12th experiment. This effect goes so far as to cause a loss of speech, a faux magnet magnetized tree, I think it was. I mean, that's amazing, you know, a loss of speech. Yes. Well, I know, but this gives us to some of these psychosomatic illnesses that people have where they do lose sight or speech or things like that. Maybe a more modern version is like chronic fatigue. You know, I know some people have chronic fatigue. They really are just knocked on their ass. They can't hardly even get out of bed and function. And yet the doctors can't find anything. It's like, my God, it's one of these categories that they, well, maybe it's chronic fatigue, whatever that is. Yeah, when it also shows the disconnect between, you know, subjective symptoms and pathology. And like, it also reminds me of research they've done where, you know, essentially it's like, if you have some type of orthopedic issue, you know, there isn't that one to one correlation between something wrong in the body and some kind of subjective pain that you're experiencing. Like people have pain without it being clear what the underlying cause is. And then, you know, people on the other side of it oftentimes will not have pain despite there being problems with the disc in your back or things of that nature. And that, I mean, it takes us right to what really interesting with the placebo effect of the surgeries. I don't know if you want to get into that. Yeah, sure. Yeah, yeah, yeah, talk about that. Yeah. So I guess the most known example of some of the listeners might be familiar with it was a study done in the early 2000s where they did orthoscopic surgery on patients' knees. I remember that. Yeah. That was a shocker. Yeah, it really, it really was. And so they assigned people to get either the real surgery treatment as usual or to get a placebo surgery and placebo surgery. Essentially, they would take patients, they would give them anesthesia, they would do an incision and then sew them back up and have them be on their way. And there was no difference between those two conditions. And there have been not many of these kinds of surgery trials to date. Really, it's a very small number, but it's actually shockingly rare to find one where a real surgery works better than a placebo surgery. And so we might have a situation where for certain types of surgeries, like those could be very strong placebo effects by and large. And that was with the orthoscopic, not a total knee replacement. Correct. I mean, you would know if you got a new knee. Yes, you would think so. Yeah, right. You would think, then orthopedics is a natural place to study this because those surgeries are for people with pain is the main condition. There's plenty of other kinds of surgeries where, obviously, you can't do sham surgery for some of them. Yeah. Well, my hip replacements, I mean, that made a huge difference for my quality of life. I was just in a lot of pain. I mean, I couldn't even stand a lecture. I had to kind of lean or sit or find a stool or something like that. And then after that, no problem. But there, it was pretty obvious right there in the x-ray. It's just bone on bone. Oh, okay. But if it was something in between, it's just a little achy sometimes and there's still tissue in there. Maybe you could try this or that. There, I could see it might work as if there's some subjectivity to measuring it. Right. Right. Yeah. I mean, there's probably subjectivity. Pain is all subjective. But I think what you're saying is that there might be the case where there's some kinds of pathologies where it really is the case that the real surgery is going to be better than the placebo, then for pathologies that are lower in severity, it might be more ambiguous. Yeah. Well, and that makes sense to me. I like to think if I have a tumor in my body and they cut it out, that's got to help. Yes. You don't want to be in the placebo group for that when they leave the tumor. Although there was that, I think it was in the 90s when they started doing full body scans. And then they became cheap enough where people just started getting them for fun, not for fun, but just general. I just want to see if there's a tumor growing in there, catch it early. But it turns out that all of us have little things growing in our bodies. Yeah. They're not really cancerous spreading tumors or just little nodules or whatever. So the risk of actually having surgery, which is not risk-free, and has side effects, and then you're going to take drugs afterwards and so on, that's not worth the risk. Yeah, both false positives and false negatives are things to be mindful of. And it's not always clear how you balance that. That's funny. I didn't realize that that was happening a while though, because that's making a comeback now. They have these scans now that are at a low enough cost where you do full body scans. I'm not inherently saying it's a bad idea exactly, but you certainly have to be mindful that there's a cost obviously to missing a pathology, but there's a cost to thinking that you found something that's actually fine. Yeah. If you have a cancer that is symptom-free like pancreatic, apparently most pancreatic cancers, by the time it's detected, it's too late. Except for that one weird one that Steve Jobs had, he had the kind that could be surgically treated, but he waited too long because of his a lot of weird ideas about alternative medicine. Oh, it wasn't familiar. Oh, yeah, no, that's what killed him. I mean, he could have had the surgery and saved him. We think, oh, yeah, I knew he died of pancreatic cancer. I didn't realize that. Yeah, he had the one time where you can tie off and cut out the part and keep the part you need or something like that for the details of that. But yeah, we did a study, a story about that in skeptic because he was into like a juice diet. He would just have nothing but fruit. And I guess he wasn't, for a while, he wasn't into bathing because we read somewhere this was not healthy until his fellow workmates said, you know, Steve, you stink. The juice thing isn't working. The same boy caught in that idea. Yeah. Yeah. All right, let's talk about psychotherapy. I mean, talk about expectation effects in placebo. What do we know there? Yeah, psychotherapy, it's tough one. I mean, it's so challenging because, I mean, psychotherapy is all about, more or less, the conversation that you have with a therapist. And so, you know, the nature of placebo and no-cebo effect has to do with like, you know, the words you use impacting patient outcomes, then, you know, psychotherapy just really hits the nail on the head. And it's something, yeah, it's something that, you know, how a therapist can go about talking with the patients, you know, they could easily, even a very good therapist, the best of intentions, you know, you can sort of see how a therapist can say something that would evoke negative expectations from a client that they're seeing, you know, even if it was something that felt benign, like, you know, well, you know, a lot of times patients, you know, take a few years to recover from depression fully, something like that. Well, that could, perhaps, for some people, actually make them worse. You know, and it, I think it sort of goes a little bit. I mean, this is a bit of a stretch, but it goes a little bit along the lines of like what Abigail Schreier has been writing about it. Yes, yes, I am glad you brought that up. Yeah, bad therapy. Yeah, yeah, and it's, you know, I don't want to draw a connection that isn't really there, but, you know, I mean, she certainly talks to a degree about how you have people that are sort of acting like therapists, but they don't really have any training in therapy. And I would guess that folks like that would probably be the most vulnerable to creating negative expectations for people that they're talking to. Yeah, Carol Taver has been on this for us. It's kept since the 90s and the recovered memory movement we followed from fairly early on. It's an old Freudian idea that there's an unconscious and you bury things in your unconscious that are painful to recall. And, and so this then got applied to childhood sexual molestation. And then that these adult patients, now this is sort of late 80s, early 90s, started encountering therapists who they were going to for various things like depression, anxiety, sleep problems, whatever, weight problems, whatever it is. And the therapist started thinking, well, this might be a consequence of having been molested as a child. And then they would ask them and the people, people would say, well, no, I wasn't. Well, I know you think you weren't, but you might have repressed the memory of this because it was so traumatic. Here, read this book, let's talk about it for the next six months. And, you know, and they kind of through the power of expectation through questioning and planting suggestions. And, you know, do you ever have any dreams where the following elements are in the dreams? Well, maybe. Well, think about that. And then we'll talk about it more next week. And week after week after week of pretty soon, they get a full blown recovered memory, so-called recovered memory. Yeah, yeah, well, and it's like, you know, Elizabeth Loftus has been studying, studying this for her entire career. And it's just, you know, it amazes me some of what she's come across that you can get people to believe that, you know, these rich stories of like, you know, I have the study right in one case, like, you know, low level crimes, like shoplifting, those kinds of things. And you can get them to recall these sort of rich histories, because allegedly the person talked to their parents and, you know, the parents talked about this event. Oh, that was the lost in the mall. Yeah, that you were lost in the mall as a child. Yeah, that's right. Okay. Yeah, I forget the specifics. But yeah, because it's, it just goes back to the fallibility of memory, you know, it does not work like a tape recorder in the way that we oftentimes think that it does and certainly wanted to. Right. So I just planted the suggest same thing with the McMartin preschool case where they were given these little children. These are, you know, like grammar school, first grade, second grade, or, no, preschool, before, yeah, before first grade, these little anatomically correct dolls, you know, and, and, you know, tell us where the teacher touched you, point to it, you know, this kind of thing. These poor kids are in these interrogation rooms without their parents and just terrible. They're not allowed to do these kind of interrogation things anymore. But you know, the children would never lie. Well, you know, they're highly influenced by adults, right? So planting the idea, the expectation that this is what you should recall and then you recall it. Yeah, that's a big problem. And yeah, these social contagions like this happen. Yeah, well, the social, yeah, the social contagion stuff. I don't know if you would call this an example of social contagion. But, you know, well, so going back actually to what you said earlier, I mean, it sounds like a bit of a Kafka trap, you know, if you say that you had this experience, then you had it. But if you say you didn't have it, well, that's just a sign that you had it, but it was repressed. So no matter what you do, the conclusion is the same. Yeah, so Carol always makes the point that, you know, there are professionally trained clinicians who have a PhD in clinical psychology from a major university. They got their 10,000 hours of training or whatever it is you have to have before you're allowed to call yourself a therapist and have a license. And so in other words, there's kind of a regulatory, not union, but you know, somebody that kind of pays attention to the quality of what's being done versus as Abigail talks about, these are just anybody that wants to call themselves a therapist. And that's not against the law, you call yourself an astrologer or a psychic and whatever. And there's, you know, no one can stop you. There's no regulatory body to control that like there is in medicine. And so yeah, you end up with these really kind of quacks or at least they're probably well intentioned. You know, I think they are. Yeah. Yeah. Yeah, I think I think they are too. But yeah, anyway, so yeah, that's a problem. It's always been a problem. And that's it. For the most part, that's a no SIBO effect. Although I suppose the plus SIBO would be if just talking to somebody helps, then why not talk to a therapist? And maybe that helps. Whatever the kind is, but maybe doesn't matter. Yeah. Well, and, you know, Shrier wrote about how you can actually have the opposite of that, where talking about negative things. Makes it worse, yes. Right. Yeah. Right. But you know, I can see it well enough. Yeah. I can see it going both ways. And you know, this gets set. Like I'm not, I don't want to come across as being anti-therapy. I'm definitely not. I sort of wonder if part of the issue is that if you want to really study the effectiveness of psychotherapy, you might just have to look out at insanely long time periods that researchers aren't accustomed to, you know, like if the patient is really going through some kind of personal history or some difficulties, you know, maybe, you know, maybe the beginning is actually really bad for the patient and they get worse for a while as they're sort of unpacking whatever is happening. And perhaps the benefit is just a little bit too far into the future. So I've wondered if, I've wondered if some of some maybe no findings in the literature could be related to the fact that the follow-up periods tend to be on the short side. Hmm. Interesting. And thought of that. Yeah. That could be right. You don't want to dwell on your problems. But on the hand, maybe having a referee conversation that's directed towards some goal and stuff like that. So I was apparently cognitive behavior therapy is the one that really does work. It's very sort of focused on what's the problem exactly and let's address that specifically. Forget what happened 25 years ago with your mother. What's the problem right now? Right. I like that idea. Well, in CBT going back to expectations, one thing that CBT and theory should do is it sort of forces people to confront incorrect expectations. So if patients just make this up, a patient has some type of social phobia and they say, "Oh no, I can't go out into a crowd. I'm going to have a panic attack." Hopefully a good therapist can say, "All right, well, let's talk about the times you've gone out into crowds in the past year." And so how many panic attacks have you had? Oh, so you've had four of them, but you've probably been out into a crowd 100 plus times. That type of exchange. Yeah, yeah. And again, with a time limit on it, we're going to spend the next six weeks addressing this systematic desensitization, all that kind of stuff. As opposed to the kind of the open end of we're going to talk forever and at 250 points. Or some marital and family counseling can be good in terms of a refereed conversation. Sometimes it's hard to talk to people in your own family when emotions are running high and nobody's being rational and no one's actually listening to the other person. But if you're sitting there and there's a third person who has no commitment to either one of you, speaking for personal experience here, you can't just bullshit the therapist like you can yourself. Because they're going to ask you, "All right, what exactly did you do and what did she do and what he said and she said and so on?" And you kind of clarify it. Each person says what they say and then you have to steal man, the other person's position. All right, tell me what you think she is saying about you and then you repeat it. And that kind of thing, I find helpful. It might be a case where good therapy helps and bad therapy hurts just to put it bluntly. The systematic desensitization too, that's interesting. And this gets at more basic questions of how do you study psychotherapy? What does it mean to talk about a placebo effect in the context? Some people have actually said that psychotherapy just is a placebo. By definition, it becomes a nuanced conversation. But there was a study that came out quite a while ago, Irving Kirsch, I believe was one of the authors on it, where they compared systematic desensitization. So this is for people that have some type of phobia and they gradually expose you to whatever stimulus is causing the anxiety. But he did a control condition where he actually shocked patients to allegedly punish their anxiety. And the idea was like if systematic desensitization works in the way that people think it works, which involves a relaxation component, then that should not be effective. And yet there was no difference between the two. So it does go back to like, what's the active ingredient of these psychotherapies? And that's very hard to say. Yeah, so interesting. All right, let's wrap it up by talking about, I'm glad you brought up Havana syndrome. Everybody but us, and now I think think we you have thought this is like some sort of sonic weapon and so on. But our author, Robert Bartholomew, is the expert on these mass psychogenic. Yes, he is. Illnesses has a chapter in here from genitals, shrinking panics to humming giraffes, the many different faces of the placebo effect. I love that you had that in there. Yeah, so Havana syndrome, do you want me to try to give you a picture? Yeah, I mean, you mentioned it was on NPR. I mean, 60 minutes that, you know, two full episodes of their show and they didn't follow. Yeah, one recently, right? Yeah, one recently going really looks like it's a sonic weapon. It's like, no, didn't you read the skeptic article? Not just skeptic elsewhere. I mean, you got to send it to them. Yeah, so Havana syndrome started in around 2017, and there were some in US intelligence officers, and it started just a very small number, only two or three or so, and they had these bizarre neurological symptoms, headaches, migraines, they sort of heard a loud noise. You know, you can read some of these reports, and I think there's some interviews. I mean, it sounds, I heart goes outside. It sounds really quite horrific. I'm not dismissing it in any way. Anyway, so a couple of reports came out and then, you know, there are sort of more and more reports that spread of people with these same types of symptoms. Again, it was concentrated in the US intelligence community, folks that were stationed abroad, many of them were in Cuba, which is where it got its name, Havana syndrome. And for a while, there was talk of it being, you know, some type of like weapon from Russia, microwave or something along those lines. And, you know, there's just no evidence for it that I'm aware of, and I've certainly looked into this a bit. And, you know, the couple of studies have come out recently where the intelligence officers that have reported essentially Havana syndrome on certain kinds of neurological markers where they do imaging and whatnot, like they're actually not different than control groups by and large. And importantly, they don't seem to show a decay over time and not a neuroscientist, but certain markers that you would expect, you know, to see a decay on, if there really was something going on in the brain. And so, you know, it's hard with these mass psychogenic illnesses, also called mass hysteria, because you can't exactly prove it, because that's just proving a negative. All you can do is say, well, there isn't evidence of anything else, and this seems to fit those types of characteristics. And that's, at least as it stands now, that's what Havana syndrome seems to be looking like. And there's been cases just all throughout history in the Middle Ages. There were people having laughing fits, you know, literally they would sort of like be out on the streets laughing until they collapse. So, witch trials, great example of this, where people were having symptoms, and obviously they blamed the witches and burned them at the stake. And so, yeah, you know, it's something that really does has happened historically. Actually, the Paris bed bug story of about a year ago was probably the same case where a lot of Parisians felt like they were having bed bugs. You know, there was a huge spike in how many exterminators were called. And, you know, yeah, there were some bed bugs, but it didn't seem to be much different than a typical hot summer in Europe. And so, yeah, Havana syndrome does seem to fit that mold. Yeah. I'm 99% Bayesian, certain there's no such weapon, and it's all psychogenic. But of course, I mean, there are real things. There really are bed bugs. And people really do get, you know, a little dizzy from various causes or whatever. So, you get a reporting effect. Like, I mean, I have aches and pains, and I have this, and that happened here and there. I just don't even tell anybody. But if all of a sudden you said, "Hey, Shurmur, you know, in Santa Barbara, there's this thing going around." And it's causing these following symptoms. I'm like, "Oh, oh, oh, hey, wait a minute. That happened to me yesterday. I think I might be part of this." And that causes headaches and bad sleep. And then I tell all my friends about it, then they tell their friends. Yeah. Right. So, it's not, I mean, the problem is, well, it's all in your head. It's not in my head. I really was dizzy or I really fell down or I really got sick. I was really nauseous. Yeah. You know, but so it's not just in your head. It's such a not a good phrase. It's, you know, there's something really going on. It's just not what you think it is. And then the expectation makes it even worse. Yeah. You know, I mean, the symptoms are real. It's a question of what's the cause of the symptoms? Yeah. So, it's not to in any way dismiss that, go back to Havana syndrome, that like, you know, I do not for a second think that these folks are faking it in any way. I think they really do have those symptoms, but do they have the symptoms because of invisible microwaves or radio waves, or do they have it due to the social contagion effect? That's the crux of it. Nice. All right. Michael, there it is. The nocebo effect from the Mayo Clinic. Very good. When words make you sick, what's the future for your next line of research or people researching this topic? I would say probably moving to how you can ameliorate the nocebo effect. Some studies on that topic, but lots, lots left to be done. So, I think that's the kind of next area that we're moving into. Nice. Okay. Well, everybody out there listening have good, positive thoughts, just in case it matters. After investing billions to light up our network, T-Mobile is America's largest 5G network. Plus, right now you can switch, keep your phone, and we'll pay it off up to $800. See how you can save on every plan versus Verizon and AT&T at tmobile.com/keepandswitch. Up to four lines via virtual prepaid card, I left 15 days qualifying unlocked device credit service ported 90 plus days with device ineligible carrier and timely redemption required. Card has no cash access and expires in six months.
