WEBVTT - The 2024 Ig Nobels, Part 2 0:00:03.080 --> 0:00:07.120 Welcome to Stuff to Blow Your Mind production of iHeartRadio. 0:00:12.960 --> 0:00:15.320 Hey, welcome to use Stuff to Blow your Mind. My 0:00:15.440 --> 0:00:16.360 name is Robert. 0:00:16.160 --> 0:00:18.840 Lamb and I am Joe McCormick, and we're back with 0:00:18.920 --> 0:00:22.120 part two in our series talking about the winners of 0:00:22.160 --> 0:00:27.520 the twenty twenty four ig Nobel Prizes. The Ignobels are 0:00:27.640 --> 0:00:31.560 awards given out each year by a scientific humor magazine 0:00:31.600 --> 0:00:35.599 called The Annals of Improbable Research to both satirize and 0:00:35.760 --> 0:00:39.519 honor scientific achievements that are likely to strike people as 0:00:39.560 --> 0:00:43.159 funny for one reason or another. We cover the winners 0:00:43.400 --> 0:00:46.919 most years, and this year is no exception. So on 0:00:47.000 --> 0:00:49.279 Tuesday in part one of this series, which, by the way, 0:00:49.280 --> 0:00:51.159 if you haven't listened yet, maybe go check that one 0:00:51.159 --> 0:00:54.880 out first. But in Tuesday's episode, we talked about the 0:00:54.920 --> 0:00:58.840 twenty twenty four Physiology Prize winner, which was a study 0:00:58.880 --> 0:01:03.360 on using the a to deliver supplemental oxygen to pigs, mice, 0:01:03.440 --> 0:01:07.039 and potentially one day, human beings. And we also talked 0:01:07.040 --> 0:01:10.680 about a classic experiment from the history of dairy science, 0:01:10.760 --> 0:01:14.119 which involved trying to stack cats on top of cows 0:01:14.319 --> 0:01:17.240 and get them all freaked out with exploding paper bags 0:01:17.319 --> 0:01:20.160 in order to understand something about milk production. 0:01:20.959 --> 0:01:23.600 Yeah, and you know, if you were, if you're impatient 0:01:23.640 --> 0:01:25.000 and you're like, just give me the full list. Don't 0:01:25.000 --> 0:01:27.120 want the fullest of winners from this year and every 0:01:27.360 --> 0:01:30.080 other year that there's been an ig Nobel Prize. You 0:01:30.120 --> 0:01:33.440 can go to Improbable dot com. That is, that's the 0:01:33.480 --> 0:01:36.920 official website, and it's all all laid out for you 0:01:36.920 --> 0:01:38.000 in a very handy format. 0:01:38.280 --> 0:01:40.360 That's right, And we're not going to be talking about 0:01:40.400 --> 0:01:42.840 all of this year's winners. We most years we don't 0:01:42.840 --> 0:01:45.080 talk about all the winners. We're just we read through 0:01:45.120 --> 0:01:47.480 them and pick out some that are especially interesting to 0:01:47.560 --> 0:01:50.360 us and focus on those to try to get into 0:01:50.360 --> 0:01:50.880 more depth. 0:01:51.120 --> 0:01:51.600 Yeah. 0:01:51.840 --> 0:01:53.840 All right, So to kick things off today, I'm going 0:01:53.920 --> 0:01:56.720 to start by talking about the twenty twenty four prize 0:01:56.760 --> 0:02:01.480 in the arena of Medicine. And this selection is one 0:02:01.480 --> 0:02:05.000 of those where the nature of the experiment is funny, 0:02:05.560 --> 0:02:08.720 but I think it actually reveals something fairly profound, in 0:02:08.760 --> 0:02:14.080 this case about medicine, medical science, and human psychology. So 0:02:14.280 --> 0:02:17.560 the prize was awarded to and as always I apologize 0:02:17.600 --> 0:02:19.960 if I'm mispronouncing anything here, but it was awarded to 0:02:20.480 --> 0:02:27.000 Leaven A. Shank Tamine Fedai and Christian Bukele, for quote 0:02:27.160 --> 0:02:31.600 demonstrating that fake medicine that causes painful side effects can 0:02:31.639 --> 0:02:34.640 be more effective than fake medicine that does not cause 0:02:34.680 --> 0:02:35.800 painful side effects. 0:02:36.400 --> 0:02:40.240 Huh, well, this is funny this. I believe we've touched 0:02:40.280 --> 0:02:42.480 on this idea before, like, how do you know your 0:02:42.880 --> 0:02:45.080 how do you come to believe your fake medicine is 0:02:45.120 --> 0:02:48.840 doing anything if it doesn't cause you some sort of sensation? Right? 0:02:48.919 --> 0:02:52.600 Yeah, Well, we've talked about this without necessarily having a 0:02:53.720 --> 0:02:56.360 solid empirical backing for it. Just kind of like the 0:02:56.440 --> 0:02:59.639 suspicion that if you're taking some kind of pseudo scientific 0:02:59.760 --> 0:03:03.359 cure or some snake oil or something that, if I 0:03:03.400 --> 0:03:05.720 don't know, makes you it real bad, or it gives 0:03:05.760 --> 0:03:08.280 you an upset stomach or something like that, it might 0:03:08.400 --> 0:03:10.919 help sell the idea while it's doing something. 0:03:12.280 --> 0:03:14.720 In my house, my wife and I have been watching 0:03:15.080 --> 0:03:19.560 the recent twenty twenty four comedy series on Netflix based 0:03:19.600 --> 0:03:22.640 on the de Cameron, and there is a character in 0:03:22.680 --> 0:03:28.440 that who is regularly being poisoned by his personal physician 0:03:28.960 --> 0:03:33.399 for a bunch of health maladies that he I think 0:03:33.400 --> 0:03:35.600 mostly doesn't have, maybe some of them he has but 0:03:35.640 --> 0:03:38.400 you know, he's kind of a hypochondriac, and he's enabled 0:03:38.400 --> 0:03:42.080 by this doctor who's always giving him various tonics and potions. 0:03:41.960 --> 0:03:43.760 Enjoying this mercury. Yeah, yeah, yeah. 0:03:43.840 --> 0:03:46.840 So he's constantly in ill health and in large part 0:03:46.960 --> 0:03:50.240 due to these treatments, and people at times pointed out 0:03:50.240 --> 0:03:52.560 to him it's like like this guy's been poisoning you. Like, 0:03:52.680 --> 0:03:55.040 of course you feel bad. What did he give you 0:03:55.080 --> 0:03:58.160 to have today? And he's like, well, well, yes, I vomited, 0:03:58.280 --> 0:04:02.480 Yes I had uncontrollable diary. But that's what healing is, like, 0:04:02.560 --> 0:04:04.800 that's the sickness leaving your body. You know. 0:04:05.080 --> 0:04:05.400 Wow. 0:04:05.480 --> 0:04:08.280 And he's really slow to doubt this position at all. 0:04:08.640 --> 0:04:12.160 Well, it's amazing how well that exact situation will play 0:04:12.160 --> 0:04:17.320 into the study and into legitimate medical uses of place. 0:04:17.360 --> 0:04:20.880 Ebos So the authors of this paper, which by the way, 0:04:21.080 --> 0:04:25.480 for the citation, the paper was called how side Effects 0:04:25.520 --> 0:04:29.479 can Improve Treatment Efficacy a randomized Trial. This was in 0:04:29.520 --> 0:04:33.600 the journal Brain in twenty twenty four, and the authors 0:04:33.760 --> 0:04:37.400 start by pointing out the obvious side effects from medical 0:04:37.440 --> 0:04:41.000 treatments are generally bad. We don't want them. You don't 0:04:41.000 --> 0:04:43.359 want them as a patient. You don't want your patients 0:04:43.400 --> 0:04:48.560 to have them. As a doctor, side effects can cause pain, discomfort, inconvenience, 0:04:48.640 --> 0:04:52.160 and concern, and in a lot of cases there if 0:04:52.200 --> 0:04:54.479 you think about the second order effects, they're not only 0:04:54.560 --> 0:04:59.000 bad because of the direct subjective unpleasantness of them. They 0:04:59.040 --> 0:05:03.560 can also lead to discontinuation of treatment itself. So if 0:05:03.560 --> 0:05:07.120 you're taking something, you know, a medicine that is very important, 0:05:07.160 --> 0:05:10.240 that's you know, helping treat your cancer or something like that, 0:05:10.600 --> 0:05:12.880 but the side effects are really bad in some cases, 0:05:12.880 --> 0:05:16.239 that can lead people to discontinue treatment that is working. 0:05:17.839 --> 0:05:20.760 So you want to avoid side effects most of the time, obviously, 0:05:20.920 --> 0:05:25.520 and this means that the researcher is developing new drugs, surgeries, 0:05:25.560 --> 0:05:28.080 and other types of treatments are always looking to find 0:05:28.120 --> 0:05:34.000 a treatment with fewer or less severe side effects on average. Furthermore, 0:05:34.279 --> 0:05:39.360 avoiding side effects also factors into which treatments doctors will 0:05:39.400 --> 0:05:43.640 prescribe or recommend to their patients, or even into how 0:05:43.839 --> 0:05:49.279 doctors sort of mentally or conversationally prepare their patients for 0:05:49.400 --> 0:05:53.440 treatments that they do prescribe. Because much in the same 0:05:53.480 --> 0:05:56.680 way that there is a placebo effect, and the placebo 0:05:56.720 --> 0:05:59.640 effect is the effect in which the belief that you 0:05:59.680 --> 0:06:04.520 are receiving an effective treatment can by itself improve outcomes. 0:06:04.920 --> 0:06:07.880 There is also the evil twin of the placebo effect, 0:06:08.040 --> 0:06:11.479 the no cibo effect, in which the mere belief that 0:06:11.560 --> 0:06:14.920 a treatment will cause pain or other negative side effects 0:06:15.320 --> 0:06:18.159 does actually cause them. That makes sense, So it works 0:06:18.200 --> 0:06:20.719 both ways. You know, I give you a sugar pill 0:06:20.760 --> 0:06:22.600 that does nothing, but I tell you it's going to 0:06:22.640 --> 0:06:24.920 treat your pain. In a lot of cases, people will 0:06:24.960 --> 0:06:27.960 actually feel less pain. There's a psychological effect going on 0:06:28.000 --> 0:06:31.720 that causes them to subjectively feel relief. Same thing happens 0:06:31.760 --> 0:06:33.919 the other way. I give you an inert sugar pill 0:06:34.200 --> 0:06:37.040 and tell you it's likely to cause severe abdominal pain. 0:06:37.120 --> 0:06:40.080 A lot of people probably will feel severe abdominal pain 0:06:40.200 --> 0:06:42.120 even though the pill isn't actually doing it. 0:06:42.720 --> 0:06:44.919 Yeah, I feel myself wrestling with this every time I 0:06:44.920 --> 0:06:47.039 get said, like my annual flu shot, you know, and 0:06:47.640 --> 0:06:50.800 you know, I have that day after where I'm I 0:06:51.160 --> 0:06:54.760 might have some flu like you know, symptoms as part 0:06:54.760 --> 0:06:57.960 of that. But then I'm like wrestling with it. It's like, okay, 0:06:58.000 --> 0:07:01.240 but is this really happening? Like how much of this 0:07:01.279 --> 0:07:03.919 is real? How much of this is my mind? You know, 0:07:04.520 --> 0:07:07.920 engaging in the no cebo effect. So yeah, it is 0:07:08.279 --> 0:07:09.120 a real, real. 0:07:08.920 --> 0:07:12.080 Thing, absolutely, And so this leads back to this question 0:07:12.160 --> 0:07:15.960 about you know, doctors prescribing their patients treatments that do 0:07:16.040 --> 0:07:19.720 have known side effects. Because with the knowledge that the 0:07:19.920 --> 0:07:23.960 expectation of bad side effects can actually make people feel 0:07:24.000 --> 0:07:27.400 bad side effects or make bad side effects worse, doctors 0:07:27.440 --> 0:07:30.120 have to be careful like how they approach the topic. 0:07:30.640 --> 0:07:32.440 You have to be honest with patients. You know, you 0:07:32.520 --> 0:07:36.800 want transparency and full disclosure about common side effects. So good, 0:07:36.880 --> 0:07:38.960 good doctors aren't going to try to hide to the 0:07:39.000 --> 0:07:42.080 fact that there are no known side effects, but also 0:07:42.600 --> 0:07:45.440 talking about side effects the wrong way in a way 0:07:45.480 --> 0:07:49.600 that maybe increases their salience could kind of no sebo 0:07:49.600 --> 0:07:53.400 effect conjure them into a painful reality for the patient. 0:07:53.680 --> 0:07:55.760 So it's a delicate balance. You know, if you're a doctor, 0:07:55.880 --> 0:07:57.840 you have to be honest about what side effects are, 0:07:58.240 --> 0:08:01.680 but you don't want to make them worse by emphasizing 0:08:01.720 --> 0:08:06.720 them in scary ways to the patient. So anyway, that's 0:08:06.720 --> 0:08:09.760 all the background. Side effects are something that are a 0:08:09.840 --> 0:08:13.200 very important part of medicine and something that doctors have 0:08:13.240 --> 0:08:16.400 to take a lot of care about but while acknowledging 0:08:16.400 --> 0:08:20.720 that side effects are generally bad the author's right quote. Here, 0:08:20.760 --> 0:08:24.120 we challenge this view and ask whether some side effects 0:08:24.160 --> 0:08:29.360 could actually lead to better treatment outcomes. This idea is 0:08:29.440 --> 0:08:33.720 motivated by the observation that side effects themselves can contribute 0:08:33.960 --> 0:08:39.680 to treatment expectations. Our hypothesis posits that even mild side 0:08:39.720 --> 0:08:44.880 effects can be indirect indicators of treatment potent c e g. 0:08:45.280 --> 0:08:49.160 Side Effects are unavoidable with a powerful drug, which can 0:08:49.240 --> 0:08:54.040 lead to positive treatment expectations. These treatment expectations are the 0:08:54.080 --> 0:08:58.000 basis for non specific therapeutic effects i e. The placebo 0:08:58.040 --> 0:09:03.640 effect that have substantial impact on treatment outcomes. So, to paraphrase, 0:09:03.760 --> 0:09:05.600 this is sort of coming back on the other side 0:09:05.640 --> 0:09:09.240 and saying we think that negative side effects could in 0:09:09.320 --> 0:09:13.679 some cases perversely lead to better outcomes for people overall, 0:09:14.160 --> 0:09:17.520 because certain side effects might make it really feel like 0:09:17.600 --> 0:09:20.280 the drug is working. Wow, it's in there, it's really 0:09:20.360 --> 0:09:22.440 doing something, and I can tell because of the way 0:09:22.480 --> 0:09:25.199 I'm feeling because of that, you know, tingling or whatever, 0:09:25.800 --> 0:09:30.360 which increases the positive contribution of placebo effects to the 0:09:30.480 --> 0:09:33.520 overall improvement in well being you get from a treatment. 0:09:34.120 --> 0:09:36.760 And this is backed up by the fact that various 0:09:37.000 --> 0:09:41.600 non therapeutic characteristics of placebos, like the color of a pill, 0:09:42.200 --> 0:09:46.439 or the understood price of a pill, or the taste 0:09:46.480 --> 0:09:49.480 of a pill, have all been shown in previous experiments 0:09:49.520 --> 0:09:53.240 to have effect an effect on outcomes, presumably through the 0:09:53.280 --> 0:09:56.680 placebo effect. Now, in their introduction, the author's right about 0:09:56.679 --> 0:09:59.880 how there's already some reason to think this hypothesis could 0:09:59.880 --> 0:10:03.160 be true, in part because of the use of what 0:10:03.200 --> 0:10:07.920 are called active placebos over inert placebos in clinical practice. 0:10:08.360 --> 0:10:12.480 So in both cases, the drug being prescribed is a placebo. 0:10:12.920 --> 0:10:16.199 It does not act directly on the underlying issue. It's 0:10:16.240 --> 0:10:19.320 not assumed to have a biological effect. It works by 0:10:19.360 --> 0:10:23.200 triggering the psychological placebo effect. So when you give somebody 0:10:23.200 --> 0:10:26.680 a placebo, you could give them a treatment that does 0:10:26.920 --> 0:10:31.000 basically nothing in reality other than trigger the psychological effect. 0:10:31.040 --> 0:10:33.280 That would be an inert placebo. Maybe it's a sugar 0:10:33.320 --> 0:10:36.559 pill or something. Or you could give somebody a pill 0:10:36.640 --> 0:10:41.280 that does something that the patient can sense, and this 0:10:41.320 --> 0:10:45.480 would be an active placebo. The preference for active placebos 0:10:45.520 --> 0:10:49.959 indicates that internal feedback from the body telling the patient 0:10:50.000 --> 0:10:53.800 that the drug is doing something may help amplify good 0:10:53.840 --> 0:10:58.440 placebo effects overall. The author's raise another important issue, which 0:10:58.480 --> 0:11:01.360 is that if side effect do have an effect on 0:11:01.559 --> 0:11:05.000 treatment outcomes, for example, by increasing the placebo effect of 0:11:05.000 --> 0:11:09.559 a given treatment, this is useful useful information in designing 0:11:09.600 --> 0:11:13.600 randomized clinical trials. You would need to take that fact 0:11:13.679 --> 0:11:17.960 into account in designing your experiments and evaluating results when 0:11:18.000 --> 0:11:20.640 testing actual drug treatments. We can talk more about this 0:11:20.760 --> 0:11:23.880 when we get to their conclusions. Anyway, the author is 0:11:23.960 --> 0:11:28.240 designed an experiment to test whether mild negative side effects 0:11:28.520 --> 0:11:32.360 would increase the placebo effect of a fake treatment, specifically 0:11:32.400 --> 0:11:37.360 a fake pain medication. So this study involved a preregistered 0:11:37.360 --> 0:11:41.320 trial of seventy seven healthy participants who would be subjected 0:11:41.400 --> 0:11:45.160 to non injurious pain from what's called a thermode, which 0:11:45.200 --> 0:11:48.280 is a device that stimulates the skin with heat or 0:11:48.280 --> 0:11:51.640 cold used for experiments like this. It can stimulate with 0:11:51.720 --> 0:11:55.520 heat or cold that will be unpleasant. It will cause 0:11:55.559 --> 0:11:59.360 a painful reaction, but doesn't hurt you. Before getting stuck 0:11:59.400 --> 0:12:02.560 with the thermo, the participants here were given a nasal 0:12:02.600 --> 0:12:05.880 spray and told that the spray might or might not 0:12:06.240 --> 0:12:10.320 include a dose of the painkiller fentanyl. Now, in fact, 0:12:10.640 --> 0:12:14.480 none of the sprays included any pain medication instead, the 0:12:14.520 --> 0:12:19.400 independent variable was whether the spray was relatively inert saline 0:12:19.760 --> 0:12:24.400 or whether it contained capsaisin, the alkaloid found in chili peppers, 0:12:24.400 --> 0:12:28.320 which of course causes a burning sensation, so in this 0:12:28.440 --> 0:12:32.880 case it would cause some burning and irritation in the nose. Now, 0:12:32.920 --> 0:12:36.120 the researchers tested this across several different experiments with some 0:12:36.559 --> 0:12:41.280 different conditions, with later phases involving a functional MRI evaluation 0:12:42.360 --> 0:12:45.600 as well as a control group who were told that 0:12:45.640 --> 0:12:48.360 there was actually no pain medication in any of the 0:12:48.400 --> 0:12:52.000 spray and so what did they find? Bingo? Even though 0:12:52.160 --> 0:12:55.800 none of the sprays actually had painkillers in them, the 0:12:55.840 --> 0:12:59.560 spray that caused a burning sensation in the nose due 0:12:59.559 --> 0:13:03.880 to this chili pepper alkaloid also apparently caused the people 0:13:03.920 --> 0:13:07.280 who received it, believing it might be a painkiller, to 0:13:07.480 --> 0:13:11.600 experience less pain from the thermode. Now, there was a 0:13:11.640 --> 0:13:15.880 commentary piece accompanying this study, also published in Brain in 0:13:15.920 --> 0:13:20.960 twenty twenty four by Kacia Witch, Helena Hartman, and Ulrique 0:13:20.960 --> 0:13:24.360 Bingle called side effects are often a curse? Can they 0:13:24.360 --> 0:13:28.800 also be a blessing? And the authors of the commentary 0:13:28.840 --> 0:13:34.120 piece right quote crucially, this greater analgesic effect, meaning pain 0:13:34.200 --> 0:13:38.920 numbing effect. This greater analgesic effect was dependent on participants 0:13:39.040 --> 0:13:43.320 believing that the occurrence of side effects indicates a more 0:13:43.360 --> 0:13:48.280 potent treatment, with this belief leading to more positive treatment expectations, 0:13:48.559 --> 0:13:52.960 which in turn resulted in increased analgesia. So does that 0:13:53.000 --> 0:13:56.200 make sense. In order for this effect to work, the 0:13:56.280 --> 0:13:59.920 patients had to believe that the burning sensation in the 0:14:00.080 --> 0:14:03.079 knows was an indicator that the drug was really working. 0:14:03.960 --> 0:14:07.520 Yes, yeah, Like, I think we've referenced this in the 0:14:07.600 --> 0:14:09.960 in the past. You know, this idea that you're taking 0:14:09.960 --> 0:14:13.839 something it is you know, it is a placebo or 0:14:13.880 --> 0:14:18.400 a snake oil if you will, but something is happening, 0:14:18.440 --> 0:14:21.840 and then you can connect that's something to what you 0:14:22.160 --> 0:14:24.760 are promised the substance will do. 0:14:25.320 --> 0:14:25.880 Yeah. 0:14:26.320 --> 0:14:28.320 Like, I always think back to an old episode of 0:14:28.360 --> 0:14:30.360 the Andy Griffith Show that I remember watching as a 0:14:30.440 --> 0:14:33.120 kid where Aunt b is buying some sort of a 0:14:33.200 --> 0:14:37.520 medicine from some guy. You know, it's a typical typical 0:14:37.600 --> 0:14:40.480 Andy Griffith Show format where there's some sort of outsider 0:14:40.520 --> 0:14:43.560 in town doing something and people were buying into their 0:14:44.160 --> 0:14:46.600 their act and then Andy Griffith has to, you know, 0:14:46.920 --> 0:14:50.000 investigate figure it out, and it turns out it's like 0:14:50.040 --> 0:14:52.960 the substance is like eighty five percent alcohol. So the 0:14:53.040 --> 0:14:55.640 various you know, old ladies around town that are that 0:14:55.720 --> 0:14:58.080 this guy's selling to, you know, they're just enjoying a 0:14:58.080 --> 0:15:01.720 little like moonshine or something. Yeah, but since it is alcohol, 0:15:01.840 --> 0:15:05.360 they are experiencing an effect. That effect is not really 0:15:05.440 --> 0:15:09.000 curing anything, but they can associate that sensation with the 0:15:09.040 --> 0:15:10.200 idea that it is working. 0:15:10.760 --> 0:15:14.560 Yes, exactly, and that connects to something that Whych and 0:15:14.640 --> 0:15:18.040 co authors in this commentary piece right about they say 0:15:18.240 --> 0:15:22.120 quote speaking of the authors of this study, they suggest 0:15:22.240 --> 0:15:25.280 that during treatment, our assessment of drug effects may be 0:15:25.360 --> 0:15:29.720 guided by simple heuristics e g. More potent treatments have 0:15:29.840 --> 0:15:33.200 more side effects, which may not always hold true, but 0:15:33.280 --> 0:15:37.160 are often a reasonable first approximation. So this might not 0:15:37.200 --> 0:15:41.440 be a true generalizable statement about medicine, but it works 0:15:41.440 --> 0:15:43.600 well enough that many of us just operate on this 0:15:43.640 --> 0:15:48.720 assumption big side effects, very potent cure. Coming back to 0:15:49.280 --> 0:15:53.600 the quote from Whychet. Although quote remarkably, Shank and colleagues 0:15:53.680 --> 0:15:57.360 found that the latter belief was strong enough to resurface 0:15:57.600 --> 0:16:03.520 even after participants had been briefed about the active placebo manipulation. 0:16:04.280 --> 0:16:08.640 While the analgesia enhancing effect of side effects disappeared immediately 0:16:09.000 --> 0:16:12.120 after the debriefing prior to the second session, it re 0:16:12.200 --> 0:16:15.800 emerged in a follow up session conducted about a week later. 0:16:16.560 --> 0:16:19.360 So they had a condition where you know that people 0:16:19.360 --> 0:16:22.560 had been doing these trials and then with one group 0:16:22.600 --> 0:16:26.080 they explained to them, Okay, here's what's going on. You're 0:16:26.120 --> 0:16:29.320 not actually getting any painkiller. This is not really happening, 0:16:29.720 --> 0:16:32.840 and so that immediately killed the effect. It broke the 0:16:32.840 --> 0:16:35.160 illusion for the people in that group. But then the 0:16:35.200 --> 0:16:38.240 people in that group who had had the illusion already broken, 0:16:38.400 --> 0:16:40.640 they came back a week later, and then the effect 0:16:40.800 --> 0:16:43.360 was working again, even though they knew what was going 0:16:43.400 --> 0:16:46.000 on at that point. It's like the time lag just 0:16:46.160 --> 0:16:49.760 allowed the somehow allowed that the magic to re coalesce 0:16:49.880 --> 0:16:50.320 or something. 0:16:50.800 --> 0:16:54.760 Oh wow, that's impressive. Like it's like there's still like 0:16:54.800 --> 0:16:57.520 a subconscious level, like there's still like an A and 0:16:57.520 --> 0:16:59.880 a B connecting there for them and they're like, yeah, yeah, 0:17:00.120 --> 0:17:02.560 made me itch or it made me sneeze. It's working. 0:17:02.920 --> 0:17:05.240 That's a right. So the authors say that this suggests 0:17:05.280 --> 0:17:08.240 it may just be a kind of deeply conditioned general 0:17:08.280 --> 0:17:13.720 association between stronger side effects a and stronger potency as 0:17:13.720 --> 0:17:25.840 a cure. So to temper these results a bit, one 0:17:25.840 --> 0:17:29.960 thing worth noting is that the effect observed from having 0:17:30.000 --> 0:17:32.919 side effects was not huge. It was not like a 0:17:33.080 --> 0:17:35.880 you know, life changing kind of difference in how effective 0:17:35.880 --> 0:17:39.360 these placebos were. But it was a statistically significant difference, 0:17:39.920 --> 0:17:43.760 and so this could potentially be influential in treatment settings 0:17:43.800 --> 0:17:47.439 and in clinical trials. So in the end, the authors 0:17:47.440 --> 0:17:50.760 say their experiments show that mild negative side effects can 0:17:50.920 --> 0:17:55.520 make a treatment or a placebo feel subjectively more powerful 0:17:55.600 --> 0:17:59.480 and effective at its desired goal. And this leads to 0:17:59.520 --> 0:18:04.359 some kind of wild sounding suggestions in their conclusion. First 0:18:04.359 --> 0:18:06.800 of all, they write, quote one could even think of 0:18:07.000 --> 0:18:11.120 artificially changing the formulation of an established drug to include 0:18:11.280 --> 0:18:16.280 mild side effects to increase treatment expectations. However, while research 0:18:16.359 --> 0:18:19.840 on open label placebo provides the idea that this effect 0:18:19.920 --> 0:18:23.560 could be used without deception, great care would be necessary 0:18:23.600 --> 0:18:27.840 to avoid any unintended harm. So I don't know. To 0:18:27.880 --> 0:18:30.640 stick with the capsaosm theme, maybe you like you smear 0:18:30.760 --> 0:18:33.320 all pills with ghost pepper juice to make sure they 0:18:33.320 --> 0:18:34.640 burn a little bit going down. 0:18:35.080 --> 0:18:38.520 Yeah, yeah, I mean I was thinking along these lines 0:18:38.560 --> 0:18:40.760 as well, but I guess, yeah, it raises a number 0:18:40.760 --> 0:18:43.840 of questions, like what if by doing this or something 0:18:44.000 --> 0:18:48.240 like this, this actually made the individual a little less 0:18:48.480 --> 0:18:50.720 likely to take the medicine or a little more likely 0:18:50.760 --> 0:18:53.560 to reject the medicine. Yeah, you know that could be 0:18:53.560 --> 0:18:56.160 a factor. Also, It's like anytime you add any substance 0:18:56.200 --> 0:19:01.560 to a medication, that open potentially opens up the space 0:19:01.640 --> 0:19:05.280 for various other health scenarios to come into play, allergies 0:19:05.320 --> 0:19:06.640 and so forth, right, exactly. 0:19:06.800 --> 0:19:11.639 Yeah, So the authors acknowledge that is a very controversial suggestion, 0:19:12.240 --> 0:19:16.040 and it would be it would face strong ethical considerations. 0:19:16.080 --> 0:19:18.560 You'd really have to think about what are the costs 0:19:18.600 --> 0:19:21.280 and benefits of doing something like that, And of course 0:19:21.280 --> 0:19:24.400 they acknowledge, like you couldn't do that secretly, Like you'd 0:19:24.400 --> 0:19:27.199 have to find a way of being transparent about the 0:19:27.240 --> 0:19:30.080 fact that like there, yeah, there's some spicy juice on 0:19:30.119 --> 0:19:34.120 this pill or something without it destroying the placebo effect 0:19:34.400 --> 0:19:38.560 benefit that you would get from it. Yeah, it's kind 0:19:38.600 --> 0:19:40.320 of hard to work out how you would balance that. 0:19:40.640 --> 0:19:41.080 Yeah. 0:19:41.200 --> 0:19:43.600 The authors also point out that there are probably limits 0:19:43.640 --> 0:19:46.359 as to how severe the side effects could be to 0:19:46.440 --> 0:19:49.440 trigger this effect, Like we don't know because it hasn't 0:19:49.480 --> 0:19:53.480 been tested yet, but like extreme pain and discomfort would 0:19:53.560 --> 0:19:56.200 likely not produce the same outcomes. In addition to being 0:19:56.320 --> 0:19:59.600 undesirable in the first place, there's probably like a sweet 0:19:59.640 --> 0:20:03.520 spot of some kind of I don't know, mildly irritating 0:20:03.600 --> 0:20:06.200 side effect that really makes it feel like the drug 0:20:06.240 --> 0:20:09.760 is more powerful, makes you feel subjectively better overall, but 0:20:09.920 --> 0:20:14.080 is not annoying or painful enough on its own to 0:20:14.280 --> 0:20:18.040 counteract that. Maybe something in the mild tingling zone. 0:20:19.400 --> 0:20:21.200 Now I don't think they got into this, but it 0:20:21.240 --> 0:20:22.840 does make me wonder about like just sort of like 0:20:22.880 --> 0:20:25.560 the bitter taste of a pill, you know, yeah, like 0:20:25.560 --> 0:20:28.200 like something that simple as sort of reminding you, oh, yeah, 0:20:28.200 --> 0:20:29.320 this is medicine I'm taking. 0:20:29.560 --> 0:20:34.440 Yeah. However, they offer so you know, the author, the 0:20:34.520 --> 0:20:37.120 original authors, and the people in the commentary piece, they're 0:20:37.119 --> 0:20:40.200 all saying, like, Okay, that idea is a little bit wild. 0:20:40.200 --> 0:20:43.520 That's kind of controversial to say you would intentionally increase 0:20:43.600 --> 0:20:48.159 mild negative side effects to make the placebo aspects of 0:20:48.200 --> 0:20:51.840 a treatment better. So they offer a different idea, which 0:20:51.920 --> 0:20:55.840 is you could potentially capitalize on this discovery by saying, 0:20:56.560 --> 0:21:00.760 when side effects are already present in a drug, doctors 0:21:00.800 --> 0:21:05.800 could try to increase the positive salience of known side effects, 0:21:06.200 --> 0:21:10.240 unavoidable known side effects instead of trying to decrease the 0:21:10.280 --> 0:21:12.520 salience of those side effects. So, you know, we talked 0:21:12.560 --> 0:21:15.760 at the beginning about how a lot of doctors know 0:21:15.880 --> 0:21:19.400 about no cebo effects, and so they will often try 0:21:19.440 --> 0:21:23.080 to frame the possibility of negative side effects in a 0:21:23.160 --> 0:21:26.159 delicate way to try to prevent them from you know, 0:21:26.240 --> 0:21:29.720 prevent them from over manifesting due to no sebo expectations. 0:21:30.160 --> 0:21:32.080 The authors here are saying, well, what if you kind 0:21:32.080 --> 0:21:35.640 of do the opposite, maybe kind of elevate the salience 0:21:35.800 --> 0:21:40.000 of mild, known unavoidable side effects of drugs, but you 0:21:40.119 --> 0:21:42.720 frame them in a positive way instead of a negative way. 0:21:43.000 --> 0:21:46.680 So you frame unavoidable pre existing side effects of drugs 0:21:46.720 --> 0:21:48.600 as a sign that it's working. 0:21:50.000 --> 0:21:51.960 All right, all right, I can I can see. This 0:21:52.160 --> 0:21:55.640 is just more about the messaging and turning the potential 0:21:55.680 --> 0:21:56.359 negative into. 0:21:56.240 --> 0:21:59.119 A positive exactly. Yeah, So being honest about what the 0:21:59.119 --> 0:22:02.080 side effects are, but framing it in a way that 0:22:02.280 --> 0:22:06.280 emphasizes these positive placebo effects, you would get from those 0:22:06.320 --> 0:22:10.760 side effects. Yeah, However, all the authors involved here clearly 0:22:10.760 --> 0:22:15.520 acknowledge that this is a delicate, tricky subject area because, 0:22:15.800 --> 0:22:18.600 as the authors of the commentary piece right quote, the 0:22:18.640 --> 0:22:22.280 framing of side effects must respect ethical standards and should 0:22:22.280 --> 0:22:27.440 not jeopardize patient autonomy and the patient practitioner relationship. It's 0:22:27.480 --> 0:22:31.119 therefore crucial for patients and practitioners to engage in joint 0:22:31.160 --> 0:22:35.160 decision making about the use of positive framing as part 0:22:35.200 --> 0:22:38.800 of the treatment. So, you know, they're saying there, like, 0:22:38.840 --> 0:22:42.679 you want to be as transparent as possible while doing 0:22:42.720 --> 0:22:46.560 this because if the patient, I mean, for one thing, 0:22:46.800 --> 0:22:50.080 that's just like baseline what a doctor should do. But 0:22:50.200 --> 0:22:53.639 also if the patient gets the feeling that they're being 0:22:53.680 --> 0:22:56.560 manipulated or the doctor is not being honest with them, 0:22:57.040 --> 0:22:59.960 then also this could lead to more negative treatment outcomes 0:23:00.080 --> 0:23:03.040 and everything. So, like, I don't know, it's a difficult 0:23:03.040 --> 0:23:05.879 thing to work out here because there the placebo effect, 0:23:06.000 --> 0:23:09.879 no cebo effect. It all necessarily relies on some amount 0:23:10.000 --> 0:23:15.159 of illusion. But you can't let that manifest as dishonesty 0:23:15.240 --> 0:23:17.600 in the clinical setting or any kind of lack of 0:23:17.640 --> 0:23:19.440 trust between the doctor and the patient. 0:23:19.760 --> 0:23:22.159 Yeah, that's a great point because you're you're you're in 0:23:22.160 --> 0:23:24.320 this realm where on one hand, you have you know, 0:23:24.440 --> 0:23:29.400 pretty hard lines concerning you know, ethical medicine and doing 0:23:29.440 --> 0:23:33.040 no harm and being transparent. But then also you were 0:23:33.080 --> 0:23:36.160