Sensory Approach to Manual Therapy
Sensory Approach to Manual Therapy
Harnessing Placebos for Enhanced Recovery
Can a simple therapeutic interaction release powerful chemicals in your brain like endorphins and oxytocin? Discover how the relationship between a therapist and client can turn an ordinary manual therapy session into a powerful healing experience. Join us as we sit down with Luana Colloca, professor at the University of Maryland and director of the Placebo Beyond Opinion Center, to unravel the profound effects of placebos in manual therapy. Luana takes us through the myriad ways trust, warmth, and competence in the therapist-client relationship can significantly enhance therapeutic outcomes.
Ever wondered how your expectations can shape your recovery? We dive deep into the impact of patient expectations and expectancy on therapeutic success. Learn how managing expectations through honest dialogue and realistic goal-setting can prevent disappointment and bolster treatment efficacy. Luana shares compelling insights into the subconscious mechanisms of expectancy and how therapists can utilize cognitive-behavioral techniques to harness these for better patient outcomes. We also uncover fascinating studies on post-operative pain management, illustrating how patient awareness of treatment can dramatically influence its effectiveness.
In our exploration of subtle cues and future directions, we touch on everything from the influence of environmental factors in therapy to the revolutionary concept of open-label placebos. Luana recounts her journey from skepticism to belief in the placebo effect, inspired by groundbreaking research. Look ahead to the future of placebo therapy as we discuss reversing impaired inner pharmacy mechanisms and personalizing treatment plans. Whether you're a therapist or simply curious about the mind-body connection, this episode promises to expand your understanding of the powerful interplay between psychology and treatment outcomes.
Please download her free manual on Placebo Effects Through the Lens of Translational Research: https://academic.oup.com/book/54240
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Welcome everybody to another podcast for the Sensory Approach to Manual Therapy. Today, my guest is Luana Kuloka, and she is a professor at the University of Maryland. She is also the director of the Placebo Beyond Opinion Center and I'm really grateful to have her as a guest today. For those of you who listened to my most recent podcast with sarah marshall, we talked a lot about placebos and he actually told me to reach out to you, and so I was very happy to attend one of the isp's webinars on placebos and see that you were the one running it. So thanks for having me, thanks for joining me today thank you very much for having me.
Speaker 2:it is a great pleasure to work with you, troy, and I look forward to this conversation.
Speaker 1:Yeah. So for my followers, for the listeners who already do a lot of placebo stuff that I talk about, I'm teaching a class coming up in June called I Am Placebo Positive and the main premise that I have behind placebos in manual therapy since I'm a massage therapist and a lot of my listeners are manual therapists the main premise that I have is that when people seek out treatment, be it any version of intervention but I'm going to stick with the idea of manual therapy, manual therapy when they seek out intervention, they get better sometimes. And when they do get better, every therapist has a theory about why they got better. Oh, it's because we did stretching, it's because we did exercise, it's because you, we changed your posture, it's because we changed how you move, and xyz, all these reasons. But before any of those reasons happen, I have this theory that there's this kind of universal underlying rule around the human body and experience, um, and it has a lot to do with allostasis and threshold.
Speaker 1:And the more I start learning about placebos, the more I'm thinking this may play into that, in that placebos seem to be variable, that transition through any one of these interventions and seem to offer a result. So my theory is that we don't know why people get better, but that any interaction we have with the client has a component that pushes them over the threshold where they feel better, and I think placebos are part of that, that threshold and I wanted to get your feedback on whether or not you thought placebo is played into the intervention process.
Speaker 2:I'm sorry, but I think placebo play a huge role because the interaction between the provider or, in this case you know, physiotherapist manual therapy, becomes so relevant to create this connection. That is the trigger to release endogenous substances, including endorphin oxytocin, because there is touching and we know that touching releases endogenous oxytocin and other factors like endocannabinoids and so on. All this cocktail of endogenous neuropeptides becomes so critical in the visiting of this placebo because sometimes it's massive, very strong.
Speaker 1:So that makes me wonder, then, at the interaction between. There's this component of interaction between the client and the therapist, and in one of the papers that you had written about you talked about it was the opioid mechanism behind the interaction between patient and therapist, and I wonder if you could talk about that a little bit more, because it seems that it plays into less in what we do with our hands, which is a very hard thing for a lot of manual therapists to wrap their brain around, because we go to school and we're taught what we do with our hands is valuable and it's also the tool of intervention, and it sounds like from some of the stuff that I hear talking about with placebos that there's this shift that what you do with your hands actually is valuable but might not be as valuable as we thought, and just how you interact is where the value lies.
Speaker 2:Well, definitely the manual component that's activated the skin receptors and there is a huge line of research demonstrating that specific receptors in the skin have an analgesic effect, in part by cuddling or by caressing, and some specific frequencies of caressing, massaging cancels have become therapeutic. But beyond that, this psychosocial context, the interaction with the persona, becomes very relevant because the words we use, the eye contact and this feeling of trust, empathy that we can infuse in the setting becomes very relevant. And I would suggest, even before using our words, to truly connect with a person intellectually, with my content, because this can become the idea setting to start the therapy, in this case the manual therapy.
Speaker 1:So it makes me wonder if the trust component to it, the interaction component, becomes so vital that for me and I haven't come across any studies across this, and I've asked other therapists, both who belong to the Massage Therapy Research Foundation and other massage therapists who have PhDs and all these things and look into the research, and we haven't come across this and I'm wondering if you've ever heard of it across this, and I'm wondering if you've ever heard of it. I would be interested in knowing is if the client doesn't trust the massage therapist or if the interaction isn't present, do we see the same results or are the results only present with that level of interaction where there's rapport and safety and trust created?
Speaker 2:Whenever we have this interaction with our patients, trust becomes relevant as well as the perception of warmth and competence. So trust, warmth, competence, expectation are cognitive factors that can play a role in placebo effects. There is literally in the literature, disentangled the role of trust versus desire and stress, expectations versus the perception of warmth or competence of the provider. So and often we realize that the expectation and you have an expectation of this physician who will help you, this therapist will help you when we trust a person. So the level of trust is definitely important.
Speaker 2:Our language, body language, not only our words, become relevant. This element have an impact on trust, perception of confidence, perception of empathy and warmth, as well as expectations. So we form an expectation about a treatment or an optical outcome based on the trust we have into the provider. So I wish we had more science to support this statement, but maybe the fact that we don't have so much science is somehow because there are so many elements like the contextual, the body language, the way the provider or the therapist talks to to the patient, that becomes overwhelmingly important.
Speaker 1:you know much more than trust, for example, so then, with that, expectation pathways are something that I actually had a question about, because when I was reading your paper on placebo and painkillers, I came across that term, expectation pathways. And I mean, I'm not an expert in neuroscience by any means, but I've been reading about it for at least 10 years now and I've been getting into some of the nitty gritty of it, and this was actually the first time I'd come across the term expectation pathways. So I was surprised by that, because I you know not that I've heard everything by any means whatsoever, but it was a new term that I thought would have been something that I'd have been familiar with. Could you sound a little bit on expectation pathways and then how they're either being satisfied or not satisfied, where the placebo is interacting with our feel-good sensations?
Speaker 2:Yes.
Speaker 2:So today we separate the concept of expectations versus expectancy. So expectation is when we ask a participant in the lab or a patient how much do you expect to improve from this intervention? From 0 to 10 or 0 to 100? 0, not at all. 100 alone maximum improvement. On the other hand, there is something that we can't quantify, and this is the expectancy. The expectancy is rather a sort of a chat LGBT of our brain, so it puts together all we see around the tools, creates an inference. I think this treatment is going to work, because Dr Troy Levine was an expert and I trust that this can happen.
Speaker 2:All this process can be so complex that we can't truly measure with one number, you know. And so the expectancy is a predictive process of a future event that cannot occur. Without even putting our mind into that, we predict a future event. In that sense, you understand that expectations can be very complex, also in terms of a neurobiological mechanism. At the neuronal level. We know that somehow to have an expectation, to be able to rate, you don't have to have a life deficit. If we ask a patient with a bad Alzheimer's, how much do we expect? We will not get an answer. To a bird's Alzheimer's, how much do we expect? We will not get an answer. And or if we ask the pet, how much do you expect? We don't get an answer. So expectation is more of a cognitive process, so putting together a desire of improvement or a sort of self-professing. On the other hand, expectancy is something that we can observe in animals without even asking, like if every day we feed an animal, that day at the same time is beyond our door, try to attract our attention and that is the predictive model. He or she knows that at that time we pivot and that creates a expectancy of an event. And this is also true in a bee, you know, sugar, a funnel or a flower. In that sense, expectancy is more powerful because it bypasses our belief system and actually becomes a prediction of a future event.
Speaker 2:And to go back to manual therapy, a patient, while driving there, while entering the door of the clinic, already has a prediction, already has an expectancy. That is beyond our ability to ask okay, welcome to my clinic. How much do you expect to recover today? That is beyond our ability to ask okay, welcome to my clinic. How much do you expect to recover today? That is the expectation. But the process of coming to see you. The process of sitting on the bed receiving the therapy first creates this level of expectancy that we can't necessarily verbalize. That is so powerful because it becomes predictive of what we call an outcome improvement.
Speaker 2:And you mentioned another concept that is so relevant, and I would love to comment on the violation of expectations, or I would prefer to say expectancy. Let's assume a patient comes to the clinic expecting to be able to solve completely the problem after the first session of the treatment. That is an unrealistic expectation and that somehow becomes a problem because when patients have such unrealistic expectations, the perception of the benefit from the intervention the manual therapy in our case creates a sort of violation between the achievable outcome and what they had anticipated. This violation sometimes abolishes completely the effects of placebo responses, but also tends to jeopardize the response to the internet, reversing what they would expect.
Speaker 1:That's why, yeah, and even if they get a positive outcome, it won't be If it's 99% but it wasn't 100%. They would still see it as failure because their expectancy was 100%.
Speaker 2:That is why I truly believe that therapists should have a conversation before starting, you know. So tell me what do you expect from this series of sessions with you? Can you elaborate on your wishes and then negotiating with them? And this is a concept that I learned from Serge Marchand and I think we demonstrate in the lab the work. But you know part of the brain that become active when we have a discrepancy between what we expect and what we perceive. So we can even explain patients that our brain, when somehow see a violation between what we can achieve and what we wish, somehow create something that is not necessarily therapeutic.
Speaker 2:So having an honest conversation where we say, well, that is the outcome that I wish to, but let's negotiate what is the outcome that will make still in your, what is the outcome that will make still you act. Let's say we can have today 10% recover, to be followed by a 20% and slow. By the end of this eight-week treatment you will resume, let's say, a range, you know, from 40 to 60% of your ability to have this performance with your leg, with your arm or with your body. So eventually that will allow to avoid this violation of expectation, for such expectancy to be completely independent, to be able to walk to bike or pain-free, and what I see is that patients are more and more interested in learning about the brain, the placebo phenomenon, the expectation phenomenon. Eventually, I think there is room to educate them.
Speaker 1:Does that mean when we're I mean like if we speak to our clients and we ask them about expectations? You just said a couple seconds ago that the expectation is valuable we want to ask those questions and get that feedback but that it is less potent than expectancy, which is bypassing the conscious part of everything, part of everything. So is there a way, have we seen a way, to tap into the expectancy? Or is that more beyond our control? Because if I as a therapist you know, like as a salesperson, as a marketing person, I could see how that would be beneficial, but as a therapist, I could also see how it's beneficial to tap into their expectancy. For example, I'm a male. If I have a client who comes in female and they have an expectancy as a male therapist or a female therapist that they might have a natural bias toward ones or the other, and if that can be used to our benefit in therapy, would that not that don't give us a greater chance of results for a pain-free lifestyle?
Speaker 2:Exactly. That is a very complex question because, while we know that, you know, you can negotiate expectations. You can ask how much do you have to improve from 0 to 100, but expectancy is a tough part because sometimes it's not necessarily accessible in a conscious way, you know, despite.
Speaker 1:Yeah, it's not knowledge that they have available to them.
Speaker 2:Yes, so there is always this predictive machine in the brain that somehow creates an interference about what they may expect. I mean, that is a little bit what we do with CBT, you know. So now we reshape patients' is a little bit what we do with CBT, you know. So now we reshape patients' ability to see the world around them and in the same way we can try to shape expectation, hoping to impact also this subconscious process of anticipation about them while they drive to the clinic, while they're sitting there, while they smell the other you know senses in the room. So absolutely true, and conversation about expectation, we can also influence expectancy.
Speaker 1:So something we can do then as therapists to help enhance what our hands are doing is to have that conversation on session one and, I imagine, every session thereafter, in case their expectations have changed. But something we can do is create an environment where expectations are clearly understood, not only from the client but for the client and the therapist together, and that would help, in theory, the effect of placebos be more powerful only because it's giving the client more of a sense that this is someone who hears me, understands me. I can trust them. They're going to stay within my comfort zone, my boundaries, all those unsaid components to healthy care.
Speaker 1:But beyond the expectations, the effect of the placebo taking place in the brain, like with not only the expectation pathways as one but even the opioid mechanism, the phenomenons in the brain. How does that play into it? Because there's the component of expectation which I think most people, whether they're neuroscience or not friendly, they can understand. I trust this person. Therefore, obviously I'll have more faith in their work. But there's actually a component it sounds like from a lot of the stuff I'm reading that there's a component in the brain where you actually help, and I think the one that surprised me the most was in your guys's paper. You talked about post-operative pain where the placebo was affected as effective as six to eight milligrams of morphine, and that was mind-blowing can you tell about that a little bit absolutely so.
Speaker 2:the paradigm that you have to is called open-hidden or cover-over. What we did. We changed our method. So patients were in the post-operative window. They received surgery to remove lung cancer and they suffered from neuropathic and musculoskeletal pain post surgery. It is quite difficult. The way we administer four different drugs from our own buprenorphine and non-opioid treatment was to either use a pump of infusion or where we say okay, eventually you will get your treatment as a therapist at the bedside, now we are going to treat you so once they learn from the therapist for this trust and say for such a contest around the therapy, we were able to amplify the benefits up to 50%. It is also true of the opposite. If we tell them now we stop the therapy for the pain therapeutic, their pain immediately goes up, and it is also interesting that it has been demonstrated despite continuing infusion of remfentanil or another opioid.
Speaker 1:if we mislead them and say, now stop the treatment, they feel pain and this somehow reverses the action of an opioid that means if, if the doctor is next to them, by the bedside, saying we're about to give you medicine, it's more effective, whereas it's just injected, without the patient being aware of it, it tends not to be as effective, even though it's the same medication given in the same dosage, same time, all that kind of stuff.
Speaker 1:But the same goes for if you say you're taking it away, and if you say you're taking it away versus it's taken away without them knowing. When you say it's being taken away, their pain intensifies comparatively to it being removed without their knowledge.
Speaker 2:Right.
Speaker 1:That is amazing.
Speaker 1:So that means if my client and if I translate what you're talking about and I know there's no papers on this, so it's a leap in logic to go from opioid injection medication to hands-on therapy, because they're not the same by any means whatsoever. But if I were to leap in logic and say to my client, if they're unconscious on my table and they're asleep and I offer treatment, treatment and I'm not telling them what's going on, what I think their injury is, if I'm not telling them what I'm doing to help them get better, versus they're conscious on my table and I'm explaining to them this is the muscle tissue I'm working, this is the fascia, this is what I'm feeling, this is why I think it's going to get better. All those things, would it? Would it be an interesting idea to think that perhaps the same thing is occurring? That if they're conscious of what treatment is being offered, in theory it should offer a more positive outcome?
Speaker 2:Absolutely. I think this is not only true in the post-operative setting, but any treatment we provide. That is why working on expectation and aspects like we mentioned can become very relevant, because definitely we can play a role in helping, you know, the expectancy network in the brain amplify the effects of any treatment.
Speaker 1:That's so interesting. One of the things I teach in my classes often is I teach students that their clients shouldn't fall asleep on the table for a multitude of reasons, but I've never correlated it to an actual potential mechanism in the brain where we correlated in the past to learning and habituation and sensitization, some other neuroplasticity concepts and concepts and behavioral neuroscience, but I never correlated to a potentially a process in the brain where the treatment is more effective, only because you've been told it's being administered, even though they're feeling the treatment, which is really interesting. Um, so does that fall into the realm of the conditioning? Because we've talked about expectation and placebo.
Speaker 1:But there's another component of the contextualization and the conditioning around it and one of the things that often people you know they walk into a spa and they'll hear, you know music, they'll see light, low lights, like my environment is not that you can see. This is my office. It's much, there's a lot more lights, it's much more therapeutic environment. But even there that therapy gives a conditioned response. They walk in, they eat with their eyes first. The first thing they see are medical charts and athletes, photos and things. So they they're conditioned to see something and have a response to it. But one of the things that you had mentioned was condition, the conditioning in humans around placebos, which I want to talk about. But the other part that was interesting was if they're conscious in the absence of consciousness. Does that mean and I didn't have a chance to look into the other papers on that but does that mean that you guys have they've done studies on people like in a coma to see if that absence of consciousness or how did that thought process come to manifestation?
Speaker 2:Well, this is an interesting question and there are two aspects A few, but only a few, studied, explored conditioning. For people who don't know what conditioning is, Conditioning is a form of learning where we associate a stimulus that can be active, like the administration of morphine with a syringe or with a scent or with the color of the world around us. So there is always conditioning stimulus and unconditioning stimulus. So some things truly work independently of the associations. So by merely associating several times, you know that injection with that active treatment producing analgesia, the master of perception of analgesia creates a condition of the response. Even when we have patients in coma, we observe this sort of conditioning defense. That is so true that sometimes, to reverse coma, people invite the relatives to sing or to recall this memory, because conditioning creates very strong memories.
Speaker 2:So how can we study conditioning and consciousness? One possibility is the extreme to study people who actually were in coma. Another possibility can be to use what we call masking effects. So we present some stimuli in a way that is so fast, milliseconds in a way that we associate in a laboratory setting painful stimuli with masking effects, where there are like two stimulus but one masking the other one so fast that our eyes can't consciously perceive that. Despite this unconscious perception, there are studies show that unconscious mechanism, layer or inconditioning determining strong placid defects. So why is that relevant?
Speaker 2:Because it suggests that we don't need only verbal suggestion or intentional conditioning, where we put a cream color blue and we reduce the intensity of the pain to create the experience of analgesia. So there are some subtle cues around us that continue to retrieve. Probably one of the best examples are what currently are called open-label placebo. Open-label placebo or placebo given like this you know, with a label, this is a placebo, there is nothing that is inside and still people respond. So one of the theories why this can happen is because our body, through our therapeutic encounter taking ginseng, taking Governalication, taking Vitalin somehow as an image of a therapeutic outcome when we take a pill and in fact a pill is much more precious in the US than in Asia, where a middling is much more powerful Based on that, we know that sub-doctor condition mechanisms may rule.
Speaker 2:Now I would like to go back to the manual therapy. The clinic, the setting is full of use. You know probably use some cream. If the cream has a smell, if there is a candle, light, phone, or even sometimes we perceive the smell of the person in front of us, that can be over the bathroom, or can be the soap or the detergent which is typical that this person always uses. All this becomes triggers for positive effects.
Speaker 1:Which almost makes it complicated. Because now, for example, I use a lot of therapeutic creams in my office that have the smell of sports environments and things like that, and so if somebody finishes a session and they walk out my door and they smell like that and the next person is waiting to come in, they're going to smell it instantly. Now if that person associates that to therapy and positive outcomes, hey, all the better. I've set myself up for success. But if that same person smells those and has a negative connection to them and goes, I don't like that. That's not what I'm looking for. I've created an environment where now I have a hurdle to surpass to get them to have more trust and more expectation. That's met. Would that also be accurate?
Speaker 1:absolutely so any placebo is a possible nocebo which we've known. You know that that's well known, but here it's even the shirt I'm wearing. If somebody's averse to the color blue, you know like in theory it could be that subtle. But anything I'm doing, from being shaved one day to unshaven the next day, to being bald or having hair like it, becomes this thing where it's almost uncontrollable. And and then how do we use those contextualized environments to enhance treatment and not necessarily taking them away? Are there any cues or guides that we've seen that really create more of a neutral environment or an enhanced environment?
Speaker 2:Some people tend to prefer more neutral environment and probably the color we use in the hospital. The majority of the hospitals are boring weight, but if we go into a children's hospital where obviously you know the joyful, playful component has become part of the target, in that case we know that definitely that color has an effect on kids. So while with kids it has been somehow easier to understand that, in others we miss that because we don't realize that in reality it's very important to have this intentional cue to somehow create relaxation and we will have a blue range of colors or, if we want something that is exciting, we will have a red red, brown color. So we don't do too much research on that as health providers, physician doctors, therapists, but those people who do marketing, they know a lot about them.
Speaker 1:There's a reason why red, white and blue are on all the ads.
Speaker 2:Exactly. They know which color they have to do the box of our cereals, they know which color a wonderful women cream has to be and they pay attention, they conduct study to somehow have this implicit association and to condition and improve the chance that we choose to that product.
Speaker 1:So that's easily understood in regards to marketing, because I think people become it's almost colloquial in our language that people understand that there's that subtle nature to what we're looking at, what's going to attract our eye. But in regards to when it comes to helping a client get better or not, it sounds like there's just a large variety of unknowns and that creating expectations consciously help limit the unknown very expectancies help limit the unknown very expectancies where there's all these unconscious expectancies that we may or may not be meeting. But the expectations also isolate onto a given field.
Speaker 2:Absolutely. The way you frame it is perfectly in line with what I'm telling you. That's become part of the therapeutic process right and very critical.
Speaker 1:So then my next question would be with what's going on with placebos and things like that, have you found a unique story in your study of placebos that for you stands out as one of the more?
Speaker 1:It can be funny or and really anything where you like. You know that's something we really didn't expect with a placebo, Because I think for me the one that stands out the most there was one that was done, that there's a foot one that I really like, but there's also which I've already talked about in my other podcast, so I want to talk about a new one that I came across, which was they had three pieces of chocolate chips on a table and one had a $1 sign to it, one had a $2 sign and one had a $3 sign, and people were asked to eat the chocolate and tell them which one was the best, and obviously everybody chose the $3 sign piece of chocolate as though it was the best chocolate, even though they all came from the same bag. And to me that was interesting because it just meant that people associated the more expensive price with higher quality, which is by far no means reality. It doesn't necessarily correlate to what's going on, but it was interesting to see that marketing-wise, they've done that. So that was a story that, for me, was unique and interesting. Have you come across any that you're like? You know it's a placebo. That was a really different expectation than we'd received or we'd predicted.
Speaker 2:There is a strong placebo response in this situation, and sometimes we can anticipate this kind of impact, mostly through experience. And that is true for any therapist too. You know, we know that some therapists are extremely good people I would use the word charismatic. So this charismatic therapist tends to utilize and attract much more patients and other people. So the same in the when we describe the placebo. Why it's so appealing, why it's so great to learn about this phenomenon, is because we have a tool to learn more about the brain functions. So resources inside our brain that are still unexplored as scientists, but also personally speaking, is something that we can somehow experience without needing a prescription. You don't have to take a psychedelic to experience a placebo response you know, it's something that belongs to our brain.
Speaker 2:Our brain, as an inner pharmacy, has some mechanism of self-healing and we know, sometimes, when we feel so good, this can be triggered by a variety of things and situations. We know that this feeling of good somehow is creating a release of endogenous substances in the brain, with this sense of well-being, with this sense of happiness, somehow, the placebo phenomenon is a way to understand more in depth the healing processes that somehow ask us to be an active component. You know intention to be intentional about healing. We can choose to be overwhelmed by the negative outcome or we can choose to be part of healing the process. Again, I'm working with Troy to get there. But if I'm thinking, oh, I'm so sad, I'm so sick and none can help me, troy, oh, I'm so sad, I'm so sick, and then I can't help it, oh, I can't, and so that's become a sub-proposal for no-sickness. On the contrary, if we exploit all this mechanism of healing that belongs to all of us, we are in tension about that.
Speaker 1:I love that. I think that's one of my favorite ways that I've ever heard anybody talk about placebos and that it's placebos because of the pharmacological processes in the brain. It gives us the opportunity to be action-driven in our healing and not passive in the healing, which is something that many individuals in manual therapy and complementary alternative medicine talk about is that we have to be active exercise, exercise therapy, eat better, you know, be outside in the sun more, like it's. It's a component of a lot of interesting health care, um, and so it's. It's really wonderful to hear it from this point of view as well. My last question before I let you go is going to be about where do you think the future is going with placebos? Because when you talk about placebos in the world, I will be honest your name comes up quite often. You had the chance to study with Benaziti. You've had the opportunity to spend a lot of time really in this world for a while.
Speaker 2:I wish to tell a little bit about myself before answering this question. I started researching the placebo phenomenon with so much skepticism. I had finished my medical degree, I had gotten my license to practice and when I enrolled in the PhD program in neuroscience I told my mentor I'm not a psychologist, I wish to do something that is valuable for patients and I don't believe in placebo. I have to see to believe so because you know there were many manipulations or deceptions that I disliked or things that are in the lab and I didn't see the translational value. So I think that level of somehow skepticism helped me to appreciate this phenomenon. So my former mentor sent me an introvert to the room. The question was super challenging Does a placebo in fact change the firing of neurons in the brain?
Speaker 2:We were studying the patient with Parkinson's and I was sitting on one side of the surgical team with the functional surgeon, the nurse and the neuropysiologist and eventually we conditioned patients three days before the surgery with papomorphine that is an open-ended agonist for some out-of-use tremor, the bradykinesia, the rigidity, and the other one was okay.
Speaker 2:Between, you know, one hole in the skull and the other arm, the patient was receiving the deep brain stimulation that's consistent with truly the brulian filling of the scalp, inserting an ear up to the base of the lung there, and every time you do the operation in one side you can start to do the other side. Everyone's to develop a very loose position. So we were giving selling solution after having exposed them to apomorphin. So we started cleaning the skin, the arm, and do the subcutaneous injection this time not apomorphin but saline solution, possibly treat the tumor, and we were recording hundreds of the cells spiking and truly, even without counting, when patients were improving, there was a reduction of the firing, as if we had given them a homorphine. That was my thing. That was an epiphany in my career. Being a skeptical person who didn't believe in placebo had to change mind.
Speaker 1:Skeptics become the best believers.
Speaker 2:Yes, through that I wanted to learn more. I wanted to have something quantifiable, but also to translate to patients. It was not enough just to study the mechanism despite. I wanted so badly to learn how the placebo effects work. But also the goal is, how can we empower patients with that? The placebo effects is in our brain, it's part of who we are. So, if that is the case, how can we improve the management? How can we improve chemo can we impose chemo? Therapy? Related the symptoms. How can we improve many of the symptoms or longer call it, or chronic fatigues that continue to become a challenge for many people? So that is why, somehow, I'm very optimistic that the science is moving forward in a direction that is unbiased and also more tangible. Somehow we put a lot of effort to understand the mechanism, but also there is a big question how this knowledge can change the way providers, therapists, offer their treatments, but also for a patient, they can go, they can read, and what I mean.
Speaker 2:Before this call, I was talking with a patient in my office and they said, actually I brought him on the TV for an interview because he was using or overusing opioids after a surgical procedure, and by you know experience that he said, dr Koloka, I was able to quit, I was able to stop completely the opioids. That to me sounded like fuck, this is a lot. It was not the goal of our study. I'm like fuck, this is a lot, it was not the goal of our study. And he actually opened up with the reporter before even sharing it with us, because we were looking only to pay a reduction. So if somehow we can discover new potential of this intentional healing and apply it to our behaviors, quitting opioids go with no pharmacology and therapy, but that's something that belonged to us, belonged to us as therapists, belonged to us as patients, and you know that sounds like a pretty beautiful place where you wanted to go.
Speaker 1:The way I remember describing it to Salish was man, if my brain really could heal my body, how wizard would that be, how magical, right like, how mythical and mysterious and straight out of a science fiction film would it be if I had the power to heal myself just with my mind? And it sounds like there's a component of that that we can do, not that we can do all of it, but it sounds like there's a percentage where the brain has the ability to help us in the healing process, beyond just thinking positive but actually biochemically creating changes.
Speaker 2:Dr. It's also forcing us to change behaviors. This comes from someone who suffered from chronic pain. I mean I become a chronic pain patient recently due to some disease. So there is a neurobiology of pain and we don't want to say that pharmacological treatments are unnecessary. On the contrary, pharmacological treatment can't be the only solution. So today, when I suffer from pain excruciatingly, very intense, I have a choice. You know, I take medication or I go to swim. So my first approach is to go to swim or to bike. So by doing that, I mean this comes from someone who knows what suffering feels. You know because I experienced by myself I level of pain. So I'm not selling to people something.
Speaker 2:Today Our science is great and it's just on scientific publications. Now it's beyond that. It's truly a way we can change our behaviors, get to know our body better and understanding that opioids treatment is not the solution. Even when we are excruciating the pain, pharmacological treatment can't be the solution. We are championing to make people aware of that. So while sometimes pharmacological treatments are needed to become critical, the encouragement is never to rely only on pharmacological treatment are needed to become critical. The encouragement is never to rely only on pharmacological treatment and try to regain this ability to control our symptoms that sometimes can be largely due to our mind.
Speaker 1:I love that. I love that. Is that what you call the psychoopsychobiological or the psychobiological phenomenon?
Speaker 2:Exactly.
Speaker 1:That's fantastic. I love that. So then, where do you see placebos going? There's two components there's the clinical and then there's the research going. There's two components there's the clinical and then there's the research. So I know that for a lot of people in research, placebos they don't like. They would rather they be removed, which obviously we can't do. But then I look at it as a clinician who loves research but who is primarily a clinician, and I sit there and say I love placebos If that is the percentage, if the placebo influence is the influence that helps my client get better, why on earth would I take that away from them? But in research it's almost the exact opposite. In research you want to know is my intervention effective or not? So that's where we are today. Where do you see the future going, both research-wise and clinical?
Speaker 2:I hope the future will help us to understand those people who are likely to benefit from placebo or not. And somehow, if we can quantify and let's assume we study 1,000 patients, that's actually the number that we've complete studying in the lab if we plot all the placebo response in a very rigorous way, there are some who are super responders. These are the people who heal by just coming to your clinic, get worse. So I envision a future where somehow we can predict those people compared to us who are super responders, and so then we can tailor our treatment For this patient. This inner pharmacy somehow is impaired, doesn't help to reach this level of benefit that we want. So now the question is can we reverse that? Can we treat? Can we even have treatments to help to heal this mechanism that are impairing some patients? That? I think we need much more science, but at least today the direction is to be able to classify patients, clusterize them.
Speaker 2:Okay, this person belongs to this pool of people that are likely to respond.
Speaker 2:This belongs to this pool of people who are likely to not respond, and these are an average of the responders.
Speaker 2:Once we gain this knowledge, you can have personalized treatment in a clinical setting, but also in a trial, you make sure that you have a balanced stratified group. In the same way, we want 50% of women, 50% of men, we want 50% of moderate responders and 50% of good responders, and maybe we will never come to the extremes. You know those people who get anguished Sometimes in the clinical trial research, a run-in phase study and many other studies that withdraw those people so they don't enroll those corresponding to a placebo, and that is some state, because those people are also those corresponding to a treatment. So eventually, by learning more about the mechanisms, we will be able to have a better design for drug or intervention development, but also precision medicine at the bedside, where you know that a certain therapeutic paradigm or it's not for some people or can be perfect for some other issues I, I love, I love how you brought the clinic and the research back together, as though they're not separate.
Speaker 1:Like that, if we can do it, if we can categorize these individuals where we have high responders, moderate responders, no responders, you can tailor your treatment so it serves a research purpose and it serves a clinical purpose.
Speaker 1:I love that.
Speaker 1:And it brings me to the question of those high responders, because we see the same thing If they respond well to placebo, they tend to respond well to hypnosis.
Speaker 1:But we also see that there was a correlation between people who respond well to placebo and hypnosis and people who spend more money unnecessarily on random things, of these things in the world where it's like, okay, xyz, miracle whatever sticker patch, necklace, bracelet, magnet, uh, chew, insole sentence phrase, smell, candle, whatever I mean any gimmick that we can possibly imagine as a marketing strategy to help people move away from chronic pain has been invented and created and sold, and so the question is for those individuals who are the highly susceptible ones, one they may or may not be getting results from those things.
Speaker 1:So if they spent, I was telling clients mine today, just before this podcast, we were talking about this and I said it's simple If I sell you a product or a service and you get better, it's not a scam. Whether it's a placebo or not doesn't matter, but if I sell you that same product and you don't get better, it's a scam. So the question is for those high responders are we seeing that they tend to be getting better even though they're responding, or is their discomfort progressing and they return to the mean averaged out with the others?
Speaker 2:Good question. We don't have the answer yet, in the sense that we don't know how much we can endorse and shift a responder, know a responder into an unresponder, or we are working in that direction in the lab to try to understand what can we do, somehow reverse an unresponder to become a responder, or how much is consistent? Let's say we start with participants today and then six months later or three years later, and the people of them is constantly responding. So the point is what we do with this. You know percentage of people who somehow were responding and then they don't respond or were not responding and then respond. So we have also these people. So that is to say that in in terms of. So that is to say that in terms of his placebo trait or you know, the status is still an open question. I want to think that is something that doesn't make sense as question, because the same way, a patient can be sick today and then healed. So I wish to hope that there is a process of restoring and healing, you know.
Speaker 1:That sounds like a really good goal to be able to try to get to that. I wish you all the best luck. I'm so thankful that you joined me today. I'm really glad that this worked out, and so easily. I mean, I reached out to you just a couple weeks ago and this was pretty fast. It was was really wonderful, and so thank you for that. But is there anything you'd like to wrap up with from your side, anything like? I know that you're with the IASP, I know that you're doing research right now. Is there anything that you want to send out to the listeners and say, hey, if you have a question or if you have interest, or if you have funding or if you have you know anything that you can do to help support some of your work as well, because I find it really interesting also absolutely and thank you for the opportunity.
Speaker 2:First, if you wish to learn more about the placebo effects in terms of mechanism, anthropology, clinical aspects, future, we wrote a book that is open access, so that means everyone can download the PDF and read for free. I think reading about this phenomenon can empower patients and therapist providers to learn more, to become more thoughtful in their interaction with patients and patients in their interaction with therapists because, as we say, it's a mutual process of healing, and also for those people who wish to donate. We create this placebo beyond opinion center, where we are very cautious with use of resources and all this. You know science, that we have been generating this through the national institute of Health, but you know any help will somehow provide additional resources to support students, trainees who are willing to step down from the remedy training or other training, to come to the lab and learn for a certain period, so everyone can help. Thank you very much.
Speaker 1:Thank you as well. Thank you so much and have a great day.
Speaker 2:Fantastic, thank you.