The placebo effect is real – but are clinical trials designed to understand it, or suppress it?
Dr Balázs Szigeti joins Paige Leacey to explain how the placebo effect shapes clinical trials, antidepressant research and psychedelic therapy. They explore why pharmaceutical companies try to minimise placebo responses, how patients can work out whether they received the active drug, and whether the apparent success of psychedelic medicine has been overstated.
Balázs is a clinical data scientist at the UCSF Translational Psychedelic Research Program and a leading researcher on placebo effects, expectancy, blinding and psychedelic medicine. He has a physics degree from Imperial College London and earned a PhD in computational neuroscience from the University of Edinburgh.
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In this conversation:
💕 What the placebo effect actually is – and why it is not “fake”
💕 How expectation can produce genuine biological and psychological changes
💕 Whether placebo-controlled trials answer the questions patients actually care about
💕 Why psychedelic studies may make psilocybin appear more effective than antidepressants
💕 What ketamine research reveals about active versus inactive placebos
💕 The limitations of psychedelic-assisted therapy
💕 Why depression and anxiety cannot always be treated as purely biological problems
💕 Microdosing, suggestibility, nocebo effects and patient expectations
💕 The relationship between psychedelics, community, rave culture and meaning
💕 Why scientific hype often rises before the evidence catches up
This discussion challenges the assumption that beating a placebo is always the most useful measure of whether a treatment helps patients. It also examines the tension between scientific research, pharmaceutical incentives and the real-world experience of people seeking relief from depression, anxiety and other mental-health conditions.
YOUTUBE + TRANSCRIPT:
(00:00) Dr Balázs Szigeti, welcome to the show. >> Thank you for having me. >> I want to talk to you about the placebo effect. Let’s get a definition on the table of what that actually is before we launch into unpacking it, whether or not it can be considered the same as fake. Yeah.
(00:17) Like whether uh there’s a deeper meaning to it than maybe what the public might who don’t do science might think. So yeah, what is the placebo effect? So there’s not like a single unified definition of it but the one that I think most people would go by it is that uh is the effect that are associated with an expectation of a benefit. So it’s kind of like a self-fulfilling prophecy kind of thing that you are doing something where you’re expecting something good to happen and lo and behold it is going to happen and uh you know the same is also happening with the
(00:43) u negative effects. uh the the evil brother of placebo effects are called the noibo effects which are sort of like the the negative side of the same coin that uh where we are telling patients that certain side effects are going to happen with the drug. Those side effects are going to happen even though if it is not really caused physiologically um by the drug itself.
(01:02) When it comes to like you know the fakeness of the placebo effect like you know there is a lot of like um a negative connotation around placebo effect that is just like a mantric and it’s not a real effect. So there is a biological basis to the to the placebo effect. It’s not just um kind of like a psychological effect. There is a real biological uh basis to it.
(01:22) But how exactly that’s work and and and the nuances of that I would say that’s very much uh research in progress. >> Okay. Can you say anything more about that that that the biological mechanism of the placebo effect? >> So the reason why this is a complicated topic is because the placebo effect works in different context. So for example I mentioned uh pain um in the last uh I just mentioned pain but like that’s one area where the placebo effect is working but that is a different mechanism for example when we are using the placebo effect let’s say in uh
(01:50) depression studies and it’s not about pain and it is about mood or the same with anxiety disorders and OCD all of these in all of these disorders we are observing placebo effects but these conditions have a different biological basis yet we are observing a placebo response in all of these conditions. Again, there is an element of like a a learning effect there with the placebo effect that uh you know in your past in your p in your past you went and visited and you know suh somebody in a white coat and you know many many times you
(02:21) felt better after it. It’s a learned response. You learn that like you know seeing people in white coat and you know when they are prescribing you something is going to make you feel better. there’s an an element of learning with the with the placebo effect and the placebo response is this broader effect that is everything that is happening in the placebo arms and um when it comes to placebo effects and the placebo response it is two different things and in the clinical trials we mostly care about the placebo response that contains all of
(02:46) the changes that are happening >> so you have the placebo effect and which is different from the placebo response but the placebo effect can be part of the placebo response >> correct >> are that good so Okay, cool. And then is that the bi like the biological thing or just the expectation the mind thing? >> You could phrase it that way.
(03:07) Like as I said like it is not like um there’s not a lot of research in this area. So it’s like hard to say whether that is the biological effect and like as I said like there is not like a universally accepted definition of what is the placebo effect and what are the placebo mechanisms. So that’s why it is difficult to um answer this but like you know that’s one way to phrase it is that the uh that like you know if there is a biological mechanism that could be you could identified it as the mechanisms of placebo and label it as the placebo
(03:33) effect and the placebo response is everything else but again this is like you know somewhat of a gray zone in the research because this is not something that is like um >> very well studied which is weird to me because like in a strange sense like you know the placebo effect is the most wellstudied condition or like you know the most studied intervention in medicine because both trials have a placebo control condition.
(03:53) So like you know we are having a lot of lot of data on it. There is strangely little research on the placebo response in itself like you know the placebo response is always there like that’s always that’s that’s what we are evaluating our drugs against yet we don’t really study like what is going on in the uh placebo arms in these trials.
(04:11) Yeah, that’s wild to me because it feels like there’s so much in that that we could discover like not just the um you know how we design better uh clinical trials for drugs but also that it kind of like it it represents this really big unknown in medicine about the the mind body connection.
(04:31) Um, I know you said that there is a biological uh piece to the placebo effect, but also when you mentioned about walking in to see the doctor and then they’re in a white coat and they give you some sort of answer to a problem that you haven’t been able to solve by yourself, that in and of itself has an effect on you because you you know when you feel you feel better about not being so alone in whatever you’re struggling with, that is also part of that placebo response.
(04:52) You know, at least maybe I’m coming at this from a biased perspective because I’m really interested in the the idea that your mind can influence matter. Sounds to me like that’s really kind of like an underlying question of how this placebo thing works. Is that fair to say? >> When you’re running a clinical study like you, you know, you’re a medical doctor and you have a drug that you believe it’s working, you’re testing it in these placebo control trials and you need to show that you’re better than placebo. So kind of like the placebo is
(05:18) the enemy. We need to show that we are better than it. There is like this negative association with it. And I think you know right now because of like you know the I’m sure we’re going to talk about psychedelics in a second but >> the issue with psychedelic medicine of course is that like you can’t really run those studies in a blinded manner and blinded is the medical term that you don’t know what you are taking.
(05:39) So you know the double blind in the double blind placebo control studies means is that neither the patient nor the the trial staff knows what um what what drug is going to be administered. And if there’s a drug that has like very strong subjective drug effects, then this model breaks down.
(05:56) And with psychedelics, it’s pretty easy to distinguish let’s say 200 micrograms of LSD from placebo. Like that’s why, you know, you can’t really run blinded studies with it. So this opened up this like this questions of that if you can’t like you know do these studies in a blinded manner then then what is the role really of the placebo effect when we are treating actual patients you know in a real life in a setting then the placebo effect is your ally.
(06:20) If you’re a good doctor, you are going to try to lean into the placebo response and elicit the biggest possible placebo response. You know what we should actually study is how to maximize the placebo response because typically what drug companies are doing, they’re trying to minimize the placebo response which makes sense from their perspective because what the regulators want them to show that their drug is better than the placebo response.
(06:42) So therefore, it is in their best interest to minimize the placebo. like drug companies have spent a lot of money figuring out how to lower the placebo response. They have like these personality questionnaires and they are screening out the placebo responders from a study and then therefore when you’re running a clinical trial like you know sometimes what they do is that they administer this personality test or like you know there’s some other tricks that people can do and they are screening them out therefore lowering the placebo response
(07:07) therefore making it easier for the drug to be better than the uh than the placebo response. And what you want to do in real life is exactly the opposite. You want to lean into it and you want to maximize the placebo response, not minimize it. >> Wow, that sounds so dodgy. like that they would be that the science uh scientists or I know researchers or you know would be screening out people that would be more likely to respond to a placebo to show that the drug had a greater effect so that the drug could get funded and then a pharmaceutical
(07:41) company could make money off the drug. That’s just like blows my mind. What what I’m interested to know though what kind of personality is more susceptible to the placebo response. So like you know suggestability and you know kind like absorption like those are the two big trades that are coming up like over and over again.
(08:00) A lot of this is research is done in the private sector. So like you know of course they’re not sharing their trade secrets. But I would say like you know suggestability and absorption those are the the two big ones that uh is kind of like out there in the literature. But you know as a lot of these things nowadays like you know a lot of the the way that these are developed is that they are just like throwing a lot of questions at people and they use some sort of machine learning algorithm to figure out like you know what combination of responses
(08:25) to those questions is predictive to perceive response and um and I would like and I need to say that you know at this point is that like you know these predictive algorithms how good they are like you know it is not like they’re better than random like that’s for sure but they’re not very good either like you know even though we have thrown a lot of resources at problem but we’re not very good at screening out who are going to be uh placebo respondents.
(08:48) It is the same with like who is going to respond to medications and in particular psychiatry has a really bad track record of um you know figuring out who is going to respond to what drug. So for example with traditional anti-depressants that they have been around for decades at this point we have spent I don’t know how many millions of dollars in finding biological signatures of who is going to respond to this SS SSRI versus that SSRI and there’s nothing that we’re really using in practice like there is this whole movement of biological psychiatry
(09:21) but in reality in real life practice we are not using any of this research in in in kind of like real world treatment It never happens that let’s say I have depression and then my psychiatrist sends me to a brain scan or like you know an EEG whatever and based on that they’re going to prescribe me a different medication and we have spent a lot of money in trying to make this work who’s with the placebo response and who’s with the drugs who is going to um respond to which again there’s a lot more research on who is going to respond
(09:52) to drugs but there’s nothing that has been consistent like typically the way it goes is that you run a study and then you are going to find some biological signature in the sample in which you have tested it. But as soon as like you know you test it in another population in another trial like that’s you know that the signal is gone and there’s like a gazillion of papers about hey you find a biological signature responding to a drug based on whatever biioarker.
(10:17) >> So how are we like what is the best way to design um drug trials to actually figure out what what works? >> Yeah. Yeah. That’s a very good question and a lot of people are thinking about this at this point. I would like to go back to a little bit to what we talked about before and that is like this screening out of placebo responders and you said I think that you know that sounds dodgy when it is dodgy but here is the reason why people are allowing it because for example if you’re running a cardiovascular trial like you know like
(10:45) some blood pressure medication yes there is a placebo response but the the gap between the typical placebo response and the drug response is much smaller in psychiatry than with other areas of medicine and that is because there is this um that the outcomes are subjective. we are in this like weird position where what we are doing I think many people recognize that it’s clearly not working but on the other hand we can’t like just say that oopsie we were wrong and like you know this like past like you know 60 years of research like
(11:12) you know it is kind of like invalid and I think that would be totally overblown but like you know we there would be an admission of guilt that like you know we have been running placebo control research for decades and actually maybe it’s not the best idea >> yeah it’s a real like battle of the egos kind of thing of like how do we maintain the fact that we have actually found out some really important things that have moved the the needle in medicine whilst also admitting that maybe we didn’t find out about them in the most efficacious
(11:39) way. >> You know, one thing that I think it’s important to recognize here is that um when you are going to a doctor with whatever medical condition, you typically have two questions and one of them is that am I better off waiting for this condition just to get better on its own or should I take medication A? That’s your first question.
(11:59) And the second question is that should I take uh medication A over medication B? Am I better off taking this drug not knowing whether I take the drug or placebo relative to taking placebo not knowing whether I take the drug or the placebo? That is what the placeboc controlled research answers. And I think it is clearly scientifically an important question that like hey is your treatment better than placebo like you know is it something that like genuinely like provides more than what is possible to do without the um the administration of
(12:29) the active drug component but this is not a patient facing question like this is something that is interesting to me like you know somebody who’s in science and is like a data geek and and I don’t want to undermine that but we need to recognize that that patients are not interested in this question.
(12:44) Um I have never seen a patient who has got better from the placebo response and they complained about it. Typically patients don’t care about whether their back pain has been uh healed by a placebo response or an active drug. They are just happy that there is that they have no there’s no back pain uh anymore. >> I’m sure that people would like the the option of not having to take a drug because drugs have side effects.
(13:08) I think most people would actually still prefer to take the drug because that’s like the real thing like you know that’s what kind of like how um you know we’ve been kind of like brought up like you know I I understand your point about the side effect but my subjective feeling is that like you know most people would still prefer to uh to do the active drug even though they’re like side effects but then there is like this oh then there’s like a like a real drug effect like you know it’s doing something like you know
(13:32) it is it cannot be fixed like you know this this this uh uh mind body division that I think that’s how most people are still um operating and this is something that I’ve been arguing for in the literature and whenever I talk publicly that instead of placebo controlled research maybe we should switch to weightless controlled research.
(13:50) like the the effect the the the sorry the the response in this weightless control trials is going to be less than the placebo response that you’re controlling for less things that is going on but it is much cheaper to do and also it is going to answer a question which is relevant to patients and if uh you know if medicine is about helping patients then we should try to answer questions that are relevant to them the whole placebo control thing like that is something that is for scientists and regulators and I don’t
(14:19) want to dismiss that. But I do feel that like, you know, we should also increase the um the the patient centricness. I’m not sure if that’s the word, but I think you know what I mean. The patient centricness of of medical research. >> Okay. So, just so I’m clear on what the weightless control is, is it kind of like a similar thing to uh place like you’re you are figuring out if there is a placebo quote unquote response to people knowing that they are on a wait list for a drug.
(14:51) Is is that kind of >> help is on the way. Help is on the way. >> Help is on the way. >> Help is on the way. And the other other part is is that like it’s just like this this this this regression to the mean effect because it is well known which I said earlier that most people sign up for a clinical trials where their symptoms are the worst.
(15:07) So it controls for like you know some of that that that that positive expectation effect that like health is on the way and it controls for just this like hey like you know just life is just like happens is sometimes up sometimes down and it controls for those things. When I hear that, I think, well, would that necessarily be appropriate for all medical conditions across the board? Are we still talking about just within the realm of psychiatric and mental health conditions? Because for some people um you know on clinical trials that they’re
(15:37) at the point where they probably don’t have any time >> you know most of these that I shared about like you know trials they are applicable to to psychiatric trials and mental health research. But let’s let’s just say that because like you know that’s broader than than psychiat and and really again the distinguishing feature is that in other areas of medicine you can actually beat the placebo response but it turns out that in mental health research is it’s very very difficult.
(16:02) So that’s why it requires that kind of like special treatment within um within medicine. And and the other point which I think is important to point out and this is this whole issue that psychedelics have opened up that typically in uh for mental health drugs like you know whether we are talking about like you know some uh benzo or traditional anti-depressants they have very strong subjective effects.
(16:27) We’re trying to help a subjective condition in mental health by definition and therefore a lot of these drugs have this very noticeable effect. And what that means is that if I am let’s say you’re enrolled in a placebo control trial and then I’m giving you the drug but of course I don’t tell you whether it’s placebo or the real thing but from the side effects of the drugs like it’s often pretty easy to figure it out and psyched are the poster boy for this problem and the technical term for this is functional and blinding. So as I said blinding is
(16:56) that you don’t know what you’re taking and then functional blinding is that even though we the research team have not told you what you’re getting but functionally you gain that knowledge just through the the experience of going through that trial. >> So what do we do what what are like what’s a better way to research psychedelic medicine if not placebo control double blind.
(17:17) So I think you know so the one thing which is important to say here is that like the regulators like the FDA at this point it looks like that they are happy to play this game like you know I do not see that there is any like movement from the regulators to change how things are uh going to be done.
(17:33) So you have a placebo control a double blind placebo control trial which is the gold standard in um medical research including um psych uh psychiatric um and mental health research and that is where you’re giving the you the the participants of the trial and then also the researchers of the trial don’t know who is getting the placebo and who is getting the pharmacological intervention.
(17:58) Um and you were saying previously that in any sort of clinical trial that is testing subjective experience that placebo is always going to be the placebo effect is always going to be larger because people have that hope that expectation that kind of um that suggestability or I guess like the the yeah the suggestability.
(18:22) Why is this a major or becoming more of a problem now that we’re getting into psychedelic research? Because the placebo is harder to ignore or just Yeah. Can you catch me up to speed on that bit? >> The issue is the functional unblinding that even when we are not telling patients what drug they are getting, it’s just super easy to figure it out.
(18:40) >> Even with a micro do, >> even with micro doing, yes, like you know, again, like it’s going to have like a dose response relationship. The smaller the dose, the less likely it is to happen. At the end of a trial, let’s say it’s like we are testing placebo versus LSD. And then we are asking you the patient to take a guess.
(18:56) Hey, what do you think you got? Placebo or LSD. And if you’re just guessing randomly, then the patient should get it right about 50% of the time. With psychedelic trials with the large doses, it’s somewhere around 90 to 95% of the time patients get it twice. The correct guess, it’s not 50%, it’s 95%. Which means that out of a 100 patients 95 correctly knew what they are getting.
(19:20) With micro doing like depending on the dose it’s kind of like in that 70 in the lower 70% range >> and with traditional anti-depressants it’s about 60%. So, so and that would mean that if we were going to if we were just going to do uh like stick our head in the sand and continue to ignore the fact that there was this functional unblinding, which means that the placebo thing is kind of like just like almost this thread hanging on to the the uh research trial that is flailing around and not really doing anything. It
(19:52) would mean that we would become more certain about the fact that psychedelics worked better than placebo because you wouldn’t have a strong enough placebo. You wouldn’t have strong enough data around the placebo because you know people know whether they did or didn’t get the psychedelic. Is that kind of am I understanding that correctly? >> It just defeats the purpose of doing placebo control studies because then you know if you know that what you’re getting then of course like you know like everybody people will know that. So
(20:19) when this issue put on the map and actually one of my earlier studies on micro doing I think that was one of the papers that started to talk about it and in in in the context of micro doing and at that time everybody was thinking that if you know that you have taken the psychedelics then you are going that’s going to activate like positive expectation effect like you know next time you’re going to a cocktail party you are going to be that interesting person that like you know I’ve been in a psychedelic violent you know it’s like
(20:48) cool and jazz and whatever like you know and and what we thought is that functional blinding is going to have a bias in the treatment arms that patients are reporting you know sort of like more positive effect but now we actually do know I would not know that’s overstating it but there’s a lot of circumstantial evidence and I think this is interesting that what is actually happening is that the placebo response is much much smaller in psychedelic trials than in other kind of uh mental health interventions The issue is that the
(21:20) patients who are in the placebo are they are disappointed and uh I don’t patient yeah I’m I’m a data scientist like I don’t treat patients but when I talk to the therapist in our team like they often say that like you know patients express um disappointment and sometimes even frustration when they know that uh you know they’ve been you know kind of screwed over but like you know like nobody is signing up for a trial wanting to be in the placebo arm right like you know that just >> so interesting. I was I was literally
(21:50) going to say that before. I was I was like, I don’t know if this is appropriate, but if I was in a clinical trial, I would be pissed off that I got a placebo. And then if I had the knowledge that you had about how, you know, this potentially this like placebo control double blind study is not the best way to do the science, then I would be even more annoyed that I’d been strung along like this like, you know, arm of the research effort that didn’t really even, you know, like need to be there. to it happened with one of my
(22:20) friend who visited Portugal and wanted to buy some weed and it turned out that he spent €40 on a gram of I believe it was oregano or like you know just some like you know like green stuff like you know it was like fake weed it feels a little bit like that that like you know you sign up for these trials and >> you know participating in these trials is it’s a lot of effort like you need to come into the clinic a number of times do all of the questionnaires yada yada yada like it’s not like It takes effort.
(22:49) That’s the point that I want to make. The best example of this is actually coming from um ketamine. I think this is worth going through because it’s just like really really cool. So ketamine it’s also psychoactive just like psychedelics. So if you are testing it against an inactive placebo then this functional blinding is a big issue for the same reasons as with psychedelics.
(23:08) It’s a strongly psychoactive drug. It’s easy to distinguish it from place. that if you’re using a drug called Midallazam, which is another uh anesthetic >> as your control condition, then you can actually run studies that functional blinding is much less of an issue. It’s still not perfect, but you have significantly decreased how different middleosm feels relative to ketamine um compared to like ketamine versus placebo.
(23:37) So I’m going to simplify it a little bit but it is uh not far from reality that if you’re testing ketamine against an inactive placebo then there is functional blinding. If you’re testing ketamine against middleosm there is no functional blind. If you’re looking at the trials that use middleosm this active drug as a placebo control uh condition then the placebo responses it’s looking normal.
(24:00) So the difference in a blinded study and in a functionally a blinded study, it’s not in the treatment terms of these studies, it is in the control arm. And this is something where I spend a lot of my time now like trying to gather like evidence for it and like how how general is this phenomena, but it seems to be that this whole issue of functional and blinding patients figuring out which group they belong to, it does not biases the treatment box.
(24:25) So to give you a specific example with traditional anti-depressants I told you that the placebo response is about eight points on this Hamilton depression scale and the the treatment response is about 10 to 11 points. So the specific treatment effect this treatment versus control difference is two to three points. >> Mhm.
(24:46) Well, can you can you um for for people that aren’t used to like the point scale um that you’re referring to like what would be a layman’s a layman’s way to understand that? So like one way is like for example if I’m asking you that like you know um how how how well have you slept in the past month then like you know that two point is sort of like going from neutral to sleeping very good like typically these are measured on uh something that’s called a liker scale the two points difference is actually not not that big of an effect I told you that like regulator or the the
(25:19) placebo control trios and for example the FDA is approving a new drug they’re looking purely at this treatment versus control difference. That’s an oversimplification. That’s not entirely true. But for the purposes of a podcast, I stand by this statement. We are looking at like how much better is treatment relative to control.
(25:38) And if you’re looking up the literature, this is what most trials are reporting as well. Like this is the whole biomedical literature is focusing on this metric. How much better is your drug relative to placebo? um psychedelic studies started to come out then people have noticed that this specific treatment effect so this treatment versus control difference is six to seven points on the aforementioned Hamilton depression scale again it was two to three points with traditional anti-depressants and this is why psychedelics have generated so much
(26:08) hype that hey look the specific treatment effects is two to three times larger than with psychedelics therefore these are much better drugs with psychedelic drugs I told you that the placebo response is about half of with traditional anti-depressants. It’s about four points. Um on the hemot depression scale, the specific treatment effect is six to seven points.
(26:31) But that means that the patient improvement is just the sum of these two. It’s about 10 to 11 points. Again, that is exactly the same as with traditional anti-depressants. The the treatment response, how much patients doing better in the treatment arm, that is about the same. It’s just that this treatment versus conco is much larger with psychedelics, but that’s not because patients are doing much better in the treatment arms.
(26:55) It’s just because patients are doing much less well in the placebo control condition of psychedelics. >> So then what about if people were going to take what this like some of the science and then just go do what they’ve already been doing, which is like going to their local drug dealer and buying a couple of grams of mushrooms and being like, “Well, the science like says that it works, so I’ll just do it by myself.
(27:14) “ I know that’s dangerous, especially if we’re getting into those bigger doses, but like I I just think, you know, that’s what people are going to do. >> Oh, yeah. It’s happening. And like, you know, what you’re referring to is called like, you know, the naturalistic views. And there’s definitely like, you know, some some research on it.
(27:29) And I think, you know, that is kind of like um like then there’s a very wide spectrum of like how people are doing it. Like I’m a big proponent of it that if you are like you know with a few good friends and I don’t know you go to like a nice weekend house in the middle of the forest and then you know like doing some mushrooms or whatever that’s probably going to have mental health benefits like you know laughing six hours with your friends that’s probably pretty good medication >> big time. So I have I have no issue with
(27:55) that. But it’s very different especially if you’re like a new user and let’s say you go to a festival or a concert like you know big crowd and then you lose your friends and like you know suddenly you find yourself alone. That’s where like you know things can uh go wrong and you know you can get to a dark place quickly.
(28:12) >> Yeah. But I think that they like you’re saying that your job as a data scientist is to bring down the hype and the media is like really really hyping up psycho psychop therapy assisted or psycho psychedelic assisted psychotherapy. It’s like being really really hyped up at the moment.
(28:28) And that’s probably what people are going to do is they’re going to think that they can just take these substances wherever and it’s going to have a benefit. And if they end up at a festival like yeah, you know, I’ve been there. It’s it’s not good to be in the wrong set and setting when you’re on psychedelics and you’re not in a good place.
(28:44) >> Yeah. Yeah. And I think you know what’s important here is that like you know there is this emphasis of kind of like the the integration of the psychedelic experience and and I I don’t know I don’t like the word integration but I don’t have a better one but like you know kind of like the point is is that like you know often psychedelics like you know you kind of like see um a path forward in your life like you know or like you realize that like you know what is like one issue that you need to fix like you know maybe hey like you know
(29:09) and you need to fix that relationship with your mom or like you know call up that old friend and like you know um work things out but then you still need to do it like I have seen it so many times in sort of like you know my circle of friends that like you know you go to this psychedelic experience and then the following day you’re very motiv motivated to to follow that that like you know that that vision that you had but then you go back home and then like you know Monday 11:00 a.m.
(29:37) you still have that meeting with the boss who don’t like and just get back like you know to that to the same old patterns and I kind of feel like you know that the psychedelic therapy container like you know the medical use because it’s kind of like serious and you need to like set aside time for it that provides this extra motivation to follow through like you know what you have been experiencing or what is that vision for your life that you have done I think like in um recreational context like you know that’s where get like most easier
(30:05) is just like you know the the followup and and I think you know this is where like the the role of therapy comes in that like you know if you are meeting with somebody you know that creates a a sense of accountability and I would say at this point we just have to like you know for more data to accumulate that how like you know how effective are psychedelics without the therapy component like you know some of those trials are already happening and and they are going to happen and like what is the best model for scalability for
(30:32) psychedelics because what we do and you know I work at UC CSF and we are running these files and but like you know what we do I don’t see that this happen that happening in the real life simply because it is it’s just too inexpensive. >> Yeah. I I I I actually read something interesting about Compass that they were trying to patent the um like they were trying to patent all these like different facets of the psychotherrapeutic experience because you know and I’m sure that it’s very nuance that the reasons behind them
(31:00) doing that are are um more complex than I’m able to articulate in this pod podcast but um yeah they were trying to patent like parts of the therapeutic interaction with the um participant because they’re a big company and they have to be seen to h have some sort of exclusivity over what they’re doing in order to actually get the funding to then scale like you say and it’s just it it feels like it gets very it all gets very messy.
(31:29) Um and if you’re also saying that maybe we’ve overhyped what like the what psychedelics can actually do. Um so not yeah not only have we overhyped what they can do but they’re kind of inaccessible to a lot of people. Um and even when they are accessible to a lot of people potentially the effects are not going to be longlasting if if you’re not having integration for years and years and years um after the fact like what is the better option you know like what is a better option for treating depression or anxiety and like what’s a better option for doing science
(32:03) >> I think I like the keys is that like of course like you know like uh depression it’s not um it’s not a purely biological condition it’s not like you know you somebody coughed at you on the bus and you got the depression virus like you know it’s not like you know that there is a a bug in your system.
(32:20) It’s a lot of it is um adaptation to our personal life circumstances. >> Like if you are somebody who is struggling financially like you know have a hard time like you know paying the bills at the rent and whatnot then uh of course like you know you’re going to be probably depressed and and anxious but like you know that’s that’s not that’s that’s a social problem.
(32:40) That’s not like a a biological or a drug problem. If you think about it, we know that depression and anxiety have much more like these social roots rather than biological roots, but we are treating them as if they would be a biological problem because that way we can avoid a much more inconvenient social questions.
(32:58) A lot of people are u struggling you know financially and otherwise. But those are much bigger questions. So, let’s just pretend it’s a biological question and give researchers like, you know, some, you know, tax taxpayer money and and and I pretend that it’s going to solve. >> No, I’m starting to realize I I like that you said that and I’m starting to realize that the role of a good data scientist is to be the kind of like sayer of truth and the the kind of, you know, Yeah.
(33:27) Um, you said before bringing down the hype, but like it really is just pointing out the the blind spots and pointing out where we’re we’re pretending that something’s going to fix a problem because we don’t want to actually look in the face what the problem is. >> And don’t get me wrong, like you know, we psychedelics.
(33:43) I do feel that like there definitely benefits to them. And there are many like life circumstances where like you know that that that altered perception of a problem of your life circumstances can can can really change it or like you know can can make it better but like you know the big to me it feels like you know that is like sometimes that is helpful sometimes it’s not and um actually one more thing that I think at this point it might be good to talk about is that and the distribution of how much patients are improving with various mental health
(34:12) treatments. If you’re looking at traditional anti-depressants, it’s kind of like a flat distribution. It’s like your your typical like bal like everybody is kind of like improving more or less the same. >> With psychedelics, it seems to be much more like a biodal distribution. There’s a big batch of people who don’t improve much or at all.
(34:33) And there’s another batch of people who who have improved a lot. With psychedelics, the response is it’s um a lot more all or nothing. While with traditional anti-depressants, it’s sort of like everybody improves roughly the same amount. It’s a little bit of an oversimplification. But the point that I wanted to make is that like you know there seems to be kind of like this like thing that like psychedelics people patients who improve they tend to improve you know like a lot but there are also people who don’t improve at all. And again that is in
(35:00) contrast with traditional anti-depressants where it’s much more like kind of like everybody improves some. >> Interesting. I want to go back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back back in your life to the beginning of your science career um you studied physics and I’m guessing I mean
(35:17) well actually I’m not going to guess I’m going to ask was the thing about physics that was really interesting to you the math bit and is that kind of the connection to data science for you now >> yeah I mean like you know I’ve been just always like math as a kid like you know I was always like really good at it and then like you know what to study at university like you know you’re good at maths let’s do physics like that can take you some places.
(35:37) To be honest, that was it. I just ended up here through like, you know, a set of life circumstances, but uh you know, I’m glad that life took me here overall. >> Yeah. Yeah. It’s a fun one. Psychedelic research is a fun one. Um I also read that you were really interested in um rave culture and that was kind of why the psychedelic switching over to to psychedelics as an area of research was interesting to to you.
(36:00) And I’m just I’m wondering if like we connect all those dots. The undergraduate in um physics, interest in maths, PhD in computational neuroscience, interest in rape culture and psychedelics. Like you you must have some sort of opinion on the nature of consciousness like this this awareness that we have of um our existence that seems quite unique to humans.
(36:24) Do you have any personal theories about like how that works? what that actually is that that unique quality. Um the way like you know I think a lot of people are thinking about it in those is kind of like you know like hierarchical organizations like you know if you’re somebody who’s like a materialistic a reductionist like you know so like the hierarchy like goes like you know from top to the bottom all the way like know to the atoms to quantum fields yada yada yada that’s where you find that like that is like your your foundational
(36:50) reality and then like you know for people who are like much more let’s say like you know team consciousness who are like looking at consciousness as like more the um you know the primary legs like you know working the other way around. But I’m kind of like I’m I’m sus very suspicious of like you know this like hierarchical structure to reality like you know to me and I’m like not sure if like you know if I can express it well right now but it’s just like um it looks much more kind of like flat like I don’t believe that and like you
(37:17) know it’s not I’m not going to like this is just like what I think but it’s not like I have like a killer argument for it but I just like deeply suspicious of there would be like you know one fundamental theory of reality that just like doesn’t seem to be like realistic for me.
(37:33) I think you know there is like not like you know this like very foundational real reality. I think you know we have like just different like um you know windows into it and different perspectives but it’s not like you know that there’s like this ultimate reality at the end of the day. And so like you know to me kind of like this like culture war of like team consciousness versus team physics like you know it just like doesn’t it just doesn’t really work.
(37:56) And again I think you know it is a lot of it is just like trying to fight for that uh prime spot like you know in our in our intellectual uh culture um uh about about like you know what is what is real and and frankly just everybody wants to be the smartest and like you know if you’re somebody consciousness then of course like you know you’re going to be uh uh making that argument.
(38:16) I often feel like you know that people know the answer in their heart of heart and then they work backwards from uh from there. The reason why I became interested and uh in rave culture not just interested but like you really became a fan of it because like you know rave culture is not just about the parties and about the drugs but there is a community there like you know typically you don’t go to rave alone you go with with friends and then you meet the friends of those friends and it kind of like creates this sort of like I like
(38:46) to call it like the midsize social layer in your life as I said like you know for most adult people you have friends but tends to be like isolated and you tend to meet with them one on- one. when you go to rave like it’s often like you know it’s like 20 people going because again like you know friends of friends are joining you and I believe that like you know this is a something that a lot of people are craving and missing from their life this sort of like this you know the the tribe where not everybody is your best friend but you have some
(39:14) connection with everybody and it also creates this like flow of new people into your life you know and especially if you’re somebody who’s like you know looking for a new partner in life this is also really good because this is how you meet new people I think most people don’t like you know once you start working it’s extremely difficult to meet new people like you know in college like you know you meet with your friends you go to parties together it’s easy to meet new people there’s like a new there’s a flow of new people into your life and uh
(39:42) you know that’s also good for creating friendship and you know you find romantic partners and I think you know that is lost for most people like you know after um you know going to college or starting the PhD that was my experience that I lost that And uh and I miss that because I’m a very very social person.
(40:01) And when I started to go to raves, I realized that like you know that that that that’s where I have found it again that like you know this sort of like this like larger social group where I’m not best friends with everybody but I know a lot of people and like I’m genuinely happy to see them even if like you know we meet once or twice a year at the rave.
(40:18) It doesn’t mean that it’s a superficial connection. It just means that like you know we are like raving buddies but it it has created like you know this this circle this larger circle that goes beyond my family and my high school friends and and I feel that like you know this is kind of like the I think this is something that’s often get lost like you know discussing psychedelics that whether you’re somebody that is coming through psychedelics through wave culture or you go to like Iawaska circles or whatnot but it’s it’s a very social thing
(40:45) generally altering your state of consciousness taking drugs tends to be a social thing. And it’s not like people don’t smoke weed at home, but typically, you know, you invite your friends over and or you know, you go to and then um >> or or like, you know, especially like, you know, to to to the raves if you’re doing some MDMA or something that you typically do that with other people.
(41:05) So, it creates like, you know, these communities, these social circles, and I find that to be the isolation and loneliness. I think, you know, that’s the number one social problem. And I think, you know, rape culture like, you know, creates a a way out of that. So that’s why I like you know became interested in in uh in rape culture at that point in my life.
(41:26) Again when I was just coming out of school and again getting married which again like you know decrease the motivation to go out but I find myself lonely and and um and and and rather the way out of that. >> Yeah. Yeah. Yeah. No, I totally agree. I um I’m big fan of of uh a festival. I don’t know um if there’s a major difference between a festival and a rave but like Yeah.
(41:49) I I totally agree with that. I have I guess there is also, you know, nuance to that and and there is nuance to everything, but in my life at least, like I have um had festival friends that were, you know, fun and silly to like bump into when you’re out and about and you’re um socializing and altering your your consciousness and you can have a joke and a laugh with them and stuff.
(42:10) But I do think that some of those um relationships do actually end up being superficial. And like it can be a little bit of a um a trap to get like super involved in those communities and trick yourself into thinking that those are the people that are going to show up when a family member dies or those are the people that are going to show up when you are having trouble parenting.
(42:30) And like maybe the case is that some of those people do end up being the ones in your life that show up. But I know that there’s like yeah there’s the balance that has to be held between your friends, your um friends that you party with and um the like level to which you can rely on them for like deep long-term friendship and the level to which you’re just like I actually you know you need to be realistic with the bucket that they fall into.
(42:56) >> Yeah. I kind of feel like this is a little bit like scientific ideas like you know you have um much more than typically what you have time to work on and just kind like have to sort through them a little bit of like you know you just got to know people and some of them you just like hey this is like how deep it’s going to go and it’s 100% fine >> but like you know through that process of like meeting new people you’re going to find a few gems where like you know you really feel like that hey like this could be like a really meaningful
(43:22) friendship same with scientific ideas like you know time is a limited resource in all of our lives. So you have to be selective of where you are spending it. That’s true for uh you know scientific ideas and friendships. >> Yeah. Yeah. Yeah. No and and I do think as well like on the back on the other side of that is that you know the the rave culture and the festival culture and the consciousness altering culture can really accelerate the relationships with with um people that are actually going to stick around. Like that’s, you
(43:51) know, my my boyfriend and I got together like fairly quickly and I think that that is um because we he gave me a lift to a festival and we ended up partying at that festival together for 3 or 4 days and then after that we were like we’re in love and you know we’re still together 3 years later.
(44:07) I have also had that similar experience, you know, and this is maybe why I hold so much nuance in this realm is like I have also had a similar experience where I’ve gone to a festival, met a guy and like partied with them for 3 days and then been like we’re in love and a week or two weeks or a month later been like this is what no like absolutely this is not this is not the love of my life.
(44:28) So I think yeah, you know, it’s just it’s it’s something to keep in mind and really like the whole the the a recurring theme in this conversation has just been that there is so much hype around um around these substances and they need to be that hype needs to be approached with like a little bit more um trepidation or like a little bit more realism >> and and like you know one thing that I think it’s important kind like historical context.
(44:58) So um really for most mental health conditions we just give SSRIs or SNRIs and uh those medications have been around since the second half of the 80s so for about 40 years and since then like you know there hasn’t okay so ketamine has recently became more popular and some RTMS treatments are becoming more widely available but it’s been kind of like um there hasn’t been a lot of development in this area since like you know when it comes to like mental health related drug treatments.
(45:28) It’s not like there is like 10 to 15 different new classes of drugs and we are like developing them in parallel and see what is happening. No, this has been an area where there has been a starvation of novelty. So that’s why also this is like you know sort of like the whole field has jumped onto them because oh like there is something you know that is new here and of course like you know a big part of it is that like you know with psychedelics like you know just sort of like a cultural history there’s like something cool and interesting about them like a lot of
(45:56) interesting people have taken them yada yada yada like it it adds that element which is like very unusual for a mental health treatment like you know when SS like nobody’s doing SSRI recreationally like it’s not a cool thing to deal, right? Like, you know, nobody is going to a party and going to take some uh banzos or um you know, this is >> unfortunately that is happening.
(46:20) Um but that’s a whole >> Yeah, I think it’s like that’s definitely happening, but that’s a problematic thing. Yeah. In a um Yeah, you shouldn’t be going to parties and taking those kinds of drugs. They they’re Yep. Um that’s like addiction. we’re getting into like addiction territory when we when we talk about th those drugs being taken recreationally.
(46:40) >> Yeah. But like you know the the the the point is is that um like you know there is something kind of like unique about psychedelics that attracts a lot of people here because they are kind of psychedelic experience is like you know we can we’re researching their medical value and whatnot.
(46:54) But one thing that’s undeniable is that they are interesting like you know that is at least that you can u say about them and I do feel that like you know when it goes like you know going back to like hype and whatnot like you know this is just kind of like the natural progression of like new technologies that like there is that >> curve that I’m sure you have seen that like you know for most technologies like you know initially like you know in the early days there’s like a lot of promise and then hit a peak and then they are coming back a little bit and then
(47:18) there’s sort of like this plateau of productivity like things like you know can like eventually normal iz like >> yeah I wonder if like the that that it’s a sign of the times as well is um magic mushrooms um can they they make all these connections these like they help with meaningful connections like you mentioned earlier uh about how you can do a trip and then the insight is like oh I actually need to call my mom and talk to her about this thing and then that can be what’s blocking you in your life you do that you take that action
(47:50) and things kind of solve themselves. Um, it’s almost like magic mushrooms are really helpful for any sort of like meaning crisis that we have and we are in the midst of a more like like we’re in the midst of a meaning crisis broadly in a kind of like global meaning crisis. That’s why so many people are going back to organized religions.
(48:10) And so psilocybin and and psychedelics are kind of like the the right medicine for the time. And maybe back in the day, like after when when things became more industrialized and people were coming back from the wars, like the right medication were the right medications were SSRIs. And I wonder if like in 20 years time when your daughters are in their 30s, there’ll be a different sort of global um malaise.
(48:34) And so we’ll have to find a different kind of medicine that can um be new and interesting and work in conjunction with that actual kind of like cultural cultural issue >> and and yeah they definitely like resonant with like you know where we are in culture right now and uh yeah like you know who knows where it is going to go like you know uh here with like you know AI like you know of course like a lot of people are worried about their jobs because of that like you know how that meeting crisis is going to look like where I don’t know like 70% of the
(49:03) jobs are lost. I’m not sure if that’s going to happen. I’m not saying it’s going to happen, but like we are uh certainly living in a time where things are changing very very rapidly and it’s just impossible to calculate where it’s going to um end up and then what is going to be then the the need of the people in response to those circumstances.
(49:21) >> Yeah. Yeah. Yeah. Yeah. I mean maybe that’s kind of what I was getting to is that um psych uh psychedelics are powerful for making meaning or like reorganizing the meaning that you’ve already made and like people are having to shift and pivot. so fast at the moment because of the the rapid evolution of technology.
(49:37) That being able to like make meaning out of uh things that are uncomfortable in a way that helps you positively move forward is seems like a really important thing for people to be able to do at the moment. and maybe like the widespread availability of psilocybin um as a medicine, psychedelics more broadly as a medicine is good for this particular time, but uh after that’s all said and done and you know we’re all on some weird UBI or like you know an AI is doing our jobs and I don’t know like everyone’s got a a chip in their head
(50:05) then there’ll be some other crisis and we’ll need some other we’ll need some other thing to help us with it and who knows what that will be. Well Balage thank you so much for your time. This has been a really interesting conversation. Where can people find your work if they want to keep up to date with your research and um any talks or lectures that you’re putting out there? >> Uh so to be honest, I tend to post just on Twitter or X nowadays and it is cy like B S Y B A L A Zs.
(50:35) Uh I always I always put the the latest out there like in terms of like scientific work and also uh talks and and and and podcasts. That’s probably the best place. Okay, cool. Well, yeah, thanks again for your time. I really appreciate it. Um, and yeah, good luck with the the next lot of research that you’re doing. >> Thank you for having me.
