TODAY'S GUEST: Dr. Luana Colloca, placebo studies expert

I'm extremely happy to welcome Dr. Luana Colloca to Hard Conversations!

Dr. Luana Colloca has conducted pioneering ground-breaking studies that have advanced scientific understanding of the psychoneurobiological bases of endogenous systems for pain modulation in humans. As a result, Dr. Colloca has developed an international reputation as a leading scientist for advancing knowledge of the neurobiological mechanisms of placebo and nocebo effects with an integrative approach including psychopharmacological, neurobiological and behavioral approaches. Her research has been published in top-ranked international journals including Biological Psychiatry, Pain, JAMA, NEJM and Lancet Neurology. The impact of her innovative work is clear from her impressive citation rate and more than 130 invited lectures. Her research has been also featured on The National Geographic, The New Scientist, Washington Post, Science daily, Boston Globe, The New Yorker Time, Nature, The Guardian, The Wall Street Journal, News and World Reports, COSMOS (Australia), The Australian, and USA Today. Dr. Colloca has been honored with prestigious awards such as the 2017 Wall Patrick International Award from the International Association for Study of Pain and the Dubner Award among others.

• Social Media:

• Twitter - @CollocaLuana

• WEBSITE:

  https://www.nursing.umaryland.edu/directory/luana-colloca/

YOU'LL LEARN

• The placebo and nocebo effects

• How the placebo effect is similar to erectile non-cooperation

• Tips on PDE-5 Inhibitors like Viagra, Cialis, and Levitra

• How the placebo effect is similar to aspects of chronic pain

• Practical tips for partners of guys struggling with erectile dysfunction

• The benefits of online sex therapy

• And more!

THANK YOU FOR LISTENING to my male sexuality and sex therapy podcast!

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About the Show

Introducing Hard Conversations, a podcast about male sexuality, and all things erectile, from the latest natural erectile dysfunction treatment to the best ed medical treatment. Therapist Tim Norton expands the conversation about male sexuality, adds context to why we struggle as a society to have hard conversations and breaks down how in a sex-positive environment there really is no room for taboos, judgment, or shame when it comes to penises.

YOUR online sex therapy and couple’s therapy HOST:

Tim Norton is a sex positive sex therapist working in private practice. He offers online therapy, online sex therapy, online sex coaching, and therapy and coaching for somatic symptom disorder.

Tim obtained his bachelor’s and master’s degrees from the University of Southern California. Tim is a proud member of American Association of Sex Counselors, Educators, and Therapists (AASECT), the Los Angeles Sexological Association, and works part-time with the Pain Psychology Center in Beverly Hills.

Hard Conversations Podcast Transcript

Luana Colloca

[00:00:00] Tim Norton: Hello, and welcome to hard conversations. So very excited for my next guest, Dr. Luana Colloca is a national Institute of health funded faculty at the university of Maryland school of nursing. Dr. Colca holds an MD a master's degree in bioethics and a PhD in neuroscience and completed a postdoc training at the Karolinska Institute in Stockholm, Sweden, and a senior research fellowship at the national institutes of health in Bethesda.

Over the last 17 years, Dr. Colloca has conducted pioneering groundbreaking studies that have advanced scientific understanding of the psycho neuro-biological bases of endogenous systems for pain, modulation and humans, including the discovery that the vassal prescence system is involved in the enhancement of placebo effects with a dimorphic effect.

Currently her team conducts basic and translational research on genomics of oral facial, chronic [00:01:00] pain brain mechanisms of expectancy and observationally induced, hyperalgesia, SIA, and an immersive virtual reality. As a result, Dr.  Colloca has developed an international reputation as a leading scientist for advancing knowledge of the neuro biological mechanisms of descending pain, modulation, placebo, and nocebo effects with an integrative approach, including psychopharmacological neuro-biological and behavioral approaches.

The impact of her innovative work is clear from our outstanding publications citation rate and numerous invited lectures worldwide. Her research has also been featured on the national geographic, new scientists, Washington post science, daily, Boston globe, new Yorker nature, the guardian wall street journal and USA today.

Dr. Colloca has been recently honored with prestigious awards, including the 2016 Wal Patrick international war for basic research on pain mechanisms by the international association for the study of pain. [00:02:00] Wow. That is quite a bio right there. Thank you so much for appearing on hard conversation. 

Luana Colloca: Thank you very much.

Tim Norton: You're welcome. So. I started learning about placebos. I think we all learn about placebos in like an intro to psychology class. And I think it's. It's probably the most fascinating thing that we learn in all of college, but, but it's just like one day we're where you tell a bunch of freshmen, Hey, this happens with some empty pills and it changes the way people feel and, and, and, and in a really effective way, but Oh, but we don't really know much about it.

So let's go on to the next chapter and that's, that's all we ever think of it. And everybody knows. Everybody will say something like, Oh, that's just the placebo effect. I think that's a weird thing to say because the placebo effect is [00:03:00] incredible. So, and you, you know, a lot about placebos? 

Luana Colloca: Well, my original idea, when I finished your mind training us of this issue to learn more about.

Our brain and, um, I love, uh, cognitive neuroscience. So I started a PhD in neuroscience and, um, my mentor, Fabrizio Benedetti, um, is one of the world's expert on this phenomenon. So when I actually started my PhD, I told them I'm a physician. I would like to do something. Cause I just relate to medicine. So I had the sort of a bias that the placebo effect was more, a psychological phenomenon somehow related to biases, but not necessarily relevant in medicine.

And I add them. I have to be funny when I'm finally, I was studying the placebo effects in the surgical room with a Parkinsonian patients. We were recording. [00:04:00] Yeah. I have a single neutrons from the  region and. I was, uh, according to this neurons were for the team neurosurgeons, neurologists neurophysiologists.

And when I started to seeing our neurons can change this fight. And some other characteristics, um, very much neurophysiological characteristics of the brain because patients feeling better after Tanya's injection of placebo morphine, I felt like I ended up letting him know more about this phenomenon.

So it wasn't definitely not something that I had planned to do, but, uh, In this first encounter with brain and, uh, eh, neuron, Allah discharge make me in three and a very curious about why the brain change at the level of single neurons, the [00:05:00] charge or the characteristic of the neuronal activity. When we believe that the treatment is real and can produce some benefits.

Tim Norton: Yeah. So that. I think I've read about that research. It was with Parkinson's patients and they, they felt better. Why, well, why did they receive some kind of a placebo? This 

Luana Colloca: were very severe patients with Parkinson disease. Eh, they don't respond anymore to the pharmacological treatment. There is, uh, a surgical procedure.

So the implantation of a DP brain stimulation. So we target some area over the basal ganglia in the brain where an electrode is implanted to stimulate and somehow help to recover from rigidity, bradykinesia tremor. And there's all of us to try to relieve this patient. During the longer they have a surgical procedure that's can range from eight [00:06:00] hours to 14 hours to implant in the brain electrodes.

In this particular context, we decided to study the placebo effect. Was an open question for us as a neurophysiologist, but also patients can have this sort of relief when you are on a surgical room for many, many hours, and you can't inject apomorphine because this will change the surgical procedure. So there was this doula, scopes, and mouse benefit to the patients then put out really.

During the operation, but also for us to try to understand, can we do observe some change at the level of a neuronal discharge? When patients receive a ABC book while they are undergoing the deep brain stimulation surgical procedure, we conducted a study where we decided to have different outcomes of [00:07:00] objective outcomes, a blind.

Neurologist was coming to the surgical room and, uh, was assessing the patient and to see if there is any, you're not changing the neuro logic or symptoms, but also we ask patients, how do you feel now? And they were telling us. Their perception and their feeling after receiving this super cutaneous injection of the pornography, that was merely a placebo selling solution.

And on the other side, that there was a, you know, the computer connected to the electrodes recording. Neuronal discharge. So you can imagine in front of the monitor spikes, some spikes that are the electrical activity of the neurons, and this kind of spike was then, you know, big and processed, analyzed. And we recorded many, many cells from the brain, and these are no us to this act.

Change the level of neuronal discharge in the vein [00:08:00] that's for me, it was, you know, I used to say my epiphany because I do like to study brain functions related to behaviors. So 

Tim Norton: yeah, that's, that's just so fascinating. And, and how long has there been follow-ups to that research? 

Luana Colloca: There are some, uh, in particular from a universe story to, and, uh, there are some other groups in particular in Canada that haven't been continued as rhino researcher with the texting, a placebo with bets in patients with Parkinson's disease.

That's  though, we haven't been thought of yet the thing, when we wants to understand that the neurophysiological makes any smoking. The placebo effect. We are now much more a turnover for the mechanism of, from lab. So I says to hear no pain in particular, that has been [00:09:00] the most important theory of research for placebo mechanism, but also many other disease from the other problem, the pressure and say the such a phobia and, um, Immunological and, you know, also erectile dysfunctions where there are some studies that have been funded with placebo.

Tim Norton: Right. And what are some of the more interesting results that you've heard or you've seen in the journals or some of your colleagues have done? What are some really interesting placebo effects that you've seen? 

Luana Colloca: Well, uh, my lab does, I'm a researcher on the placebo effects in pain and the world explore pain with a health participant where there is even some experimental, painful stimulations to understand our brain can process nociception, where we have an expectation of [00:10:00] feeling less pain, but also we have, um, I've been studying placebo in a chronic pain patient patients who suffer from a temporomandibular.

Pain disorder, there's TMJ patients, but also patients who suffer from fibromyalgia back pain and IBS associated with pleasure pain and, uh, the most, um,  so that the patients respond as well as pain, free people to placebo effects. They are able to get to the stronger adduction of their own pain when they believe that they can feel better.

And sometimes I win the appeal to trigger this. It's not enough to say, you know, you can feel better if we have this ability to empower you to change your mindset. So sometimes I would have words that are not so strong as merely taking a pill. So we try to understand the throne. Neuro-physiological [00:11:00] point of view, why taking a pill can trigger this kind of change in perception of symptoms.

Chronic pain. For example, also we study learning a mechanism and we expose people to, uh, segments of positive outcomes. Panter live better, live better, live several times, somehow the brain and the body learned to create this experience of reduction of the pain. So I would have goal is to understand the why some people respond so well.

And reach out to the mechanism. Can we trigger and empower patients to use this kind of brain functioning to reduce their own pain, but sort of, so we know that a lot of patients that no matter what they can get real real for sugar pill, ed English circle, uh, you know, reshaping of their expectations doesn't answer the anything.

Now what our goal is to try to understand that this variety of, um, you know, [00:12:00] responses when it comes to placebo effects, people that can't reduce their pain and experience very strong benefits in some other moderately can feel better. Some others cannot have an experience of a placebo effects. 

So in my lab  now the main question is to try to understand in real world setting, can we harness placebo effects and the mechanism of placebo effects to help patients manage their pain better.  And why don’t people respond and some other people do not respond. How can we predict this in advance and tailor the treatment to their needs?

Tim Norton: Yeah, I bet you have a ton of theories because it you're starting with this belief. These people have a belief that they either they can be out of pain or that nothing's really wrong with them or that you guys know how to help them. [00:13:00] And then in a laboratory you give that, is it usually a pill or do you do buzzers or do you do other kinds of things?

Luana Colloca: Well, it is interesting that you mentioned that many times chronic pain patients do not have any beliefs because they have so many, eh, you know, negative experiences, but what we start to do with listening to them, realize that in this time, that's usually limits each patient with the consenting or collection over the medical history I know this, - they say my physician doesn't listen to me. There’s nothing special. I do my procedure as a scientist. They come to the lab before I search, but I listen to them. That is part of. Any informed consent process. You're supposed to explain things to answer questions. And of course in this process, they start to tell their stories, their pain, [00:14:00] and the first encounter that I think make a difference is coming to a laboratory setting where we all wear white coats and listen to them.

The second step  would be our procedure that we arrange from a sugar pills, placebo pills which we provide in an open fashion, what we call “open label placebo.” They know that we use placebo and we tell them in the lab that, you know, we are interested in to see how merely taking a pill because of, you know, about, I told the mechanism from classical conditioning can trigger a response in their body.

 And they say, you know, I want to try it. I try many things, so why not?  So they take the placebo pill, usually that is a label placebo. I have some fields here around, but no [00:15:00] deception. And I think that is one of the main, uh, you know, changing shifts because deceptive placebos ever been used since ever it's the Eastern medicine.

And we know that, uh, you know, charismatic physicians, Shamani and many other, you know, therapists know the power of this interaction when you create this connection with your patient and you use whatever - can be a rock, can be a sugar pill, or needling patients. This can create a very strong context to release substances in the brain and making this perception of healing, this natural healing.

And the challenge was okay, we wanted to use this in that ethical way. Can we tell patients, this is just a placebo, that means sugar pills, ______ pills, saline solution. And, um, you don't have to [00:16:00] believe. So that is why the learning mechanism is this kind and some other theories that were developed at around open label placebo can be so relevant because merely the act of taking something can trigger a change. And that is the same, uh, you know, somehow placebo effects that we see when people feel so good after taking the Viagra pill or after taking a pill for another symptom like anxiety or, okay or this speech and, um, if I take a pill before that, I feel more relaxed, things like that. 

Yeah. So,fortunately I mean, the placebo doesn't have to have a specific sugar pill for each different kind of symptom. There is something common that we call placebo component that is merely part of any [00:17:00] active treatment, no matter if we use opioids, antibiotics, or, you know, antidepressant there is always a placebo component. 

And this sort of placebo component has a special role in pharmacology, because when the drug is very active, it can produce a very small placebo part, but if whatever drug that merely work, the placebo components can be so large that of course, can produce this wonderful outcome, but not because of the real ingredient of the treatment, rather the placebo component that is still real.

Tim Norton: Very very real. You mentioned a minute ago that the act of taking a pill involves classical conditioning. And by [00:18:00] that I think that you mean that as we grow up, we,  take pills from a young age and, and we, we get this message from our parents that this is going to make you better. And, and this vitamin is gonna make you stronger. And sometimes you take a Tylenol and you actually feel a little better. And once you do that for years, some people are prepared, physiologically to heal from the act of taking a pill. 

Luana Colloca: I'm glad that that's you mentioned that the cultural component is extremely relevant when we study placebo effects.  We had this anthropologist, one in particular of Mormon from university of Michigan, put out a couple of years ago, beautiful pieces on how placebo responses and placebo effects can vary across cultures.

For example, if we provide injections as painkillers for Europeans, they tended to respond much better [00:19:00] than receiving a pill because injections have power, but even surgical procedures are the strongest trigger of placebo effect.  So ________ , somehow treat larger placebo responses. But if we move it to Americans, a pill works much better than for example, an injection. So there is this switch how merely the way we administer a drug can change a placebo responsiveness. The cultural component is becoming, you know, definitively relevant although we didn't study enough, I feel our cultural component and, you know, different approach to medicine, the can change placebo responsiveness.  

Some people recently  published some research where placebo responses [00:20:00] across trials for neuropathic pain are larger when the trial is conducted in the United States as compared to other countries like Asia or Europe, and probably we thought the authors, Jeff McGill, and some other people thought that maybe the advertising, the way we advertise about the drug on TV can produce a larger placebo effect.

Tim Norton: yes, well that would be a nice, um, A lot of people, especially a lot of people from other countries criticized the United States for advertising, for drugs. They think that's just a ridiculous thing to do. So it would be nice to know, well, at least there's one upside to that, that people respond better to them.

Luana Colloca: Exactly. And so I offer this kind of intersection between the marketing and, cultural component and placebo effects. And the effects can be a little bit [00:21:00] reconsidered because this affects our daily life. The way we choose products, the way we believe we need it to perform and that's going to be very relevant.

Tim Norton: So, but the things that you're talking about - how cultural messages could influence this and are, you know, that Americans respond better to pills than injections - We're raised to believe that it's the actual chemicals in these pills, or it's the actual treatments that are making us better. And so if it's not them, but our ideas are our beliefs are our culture actually makes such a difference. What's going on in our body or what's going on in our brain that's making us feel better?

Luana Colloca: Exactly. That is the main mechanism that what we study from a neuroscience point of view, the expectation. a chain of events [00:22:00] in the brain.

So when we believe we have an anticipation that can be conscious or sometimes even subconscious, I expect something, our brain initiates a process of predicting an outcome or a future event. So, and we have this ability to put together elements from the context around us, from our internal world, what we believe, the way we grow up, we process things and we create this very complex expectancy that can be around the treatment and an expectancy around an outcome.

I'm going to take morphine because it's very strong and this belief is so strong that even if you take a placebo and you don't know that is a sham morphine, you respond. 

So there's sort of the ability to put together elements and process and create a sort of prediction of a [00:23:00] future event is a mechanism that is a basic learning mechanism in our brain? We learn since we were children to anticipate the event by having this ability to combine our internal experience, extend that experience and create our own ability to process events and predict future events. This kind of a mechanism of anticipation of future events triggers a chain of a mechanism in the brain, starting with our cognitive area of the brain where somehow have this complex ability to create desires, beliefs, expectations, but then eventually that part of the brain communicates with many other parts of our brain to grow to the sort of inhibitory mechanism. 

But it's so powerful for example, for pain, we can send some input from top down [00:24:00] to the periphery of the brain and then to the body, inhibit the nociceptive signaling or changing our experience of the pain and the same, not exactly the same brain circles, but very similar mechanism of prediction, expectation, and modulation of outcomes can be translated to other aspects of medicine and symptoms, especially when we have a conscious perception of a symptom.

For example, if we consider something that for us, we don't have a tangible experience. If I tell you “Tim now your levels of cortisol are going to increase,” but unless you have an experience of what is an increased level of, so you can't make a difference with your expectations. But if I tell someone now your ability [00:25:00] to feel less pain and we know what that means or your ability to feel less anxious, less depressed, less tremors if we talk about Parkinson’s patient.  

Any symptom that we can have an experience of can be a modulated by this mechanism over prediction and interference with the way we experienced symptoms.   

Tim Norton: Predictions and expectations.

When I'm thinking of what this podcast deals with a lot, which is erectile issues. You know, when people want erections and they can't get them or pelvic pain, there's a lot of expectation involved in that. Like, there's a there's an expectation by my clients by a lot of men that they're not going to be able to get an erection or that they are going to have pelvic pain every [00:26:00] day, all day long. 

Luana Colloca: Yes. And that is extremely important because I feel like both of the placebo and nocebo effects the body placebo component, that is a negative expectation. If a patient, as you mentioned, can have this negative expectation that there is no chance to have an erection, this creates a sort of block per se, the strong negative expectation that can come from failure in the past, or, you know, somehow this self-prophecy convincing himself that he can't perform as he would like to in part, as I mentioned for pain or any other symptoms, the results. So the outcome, and this case the erection.

So when we talk about that, Probably that is, um, similar to pain, a very [00:27:00] complex situation where internal and external factors play a role. And the beliefs, the desires sometimes can create this violation of expectations. So somehow if you expect to do so well and you can't, there is a sort of violation of expectation that block completely placebo responses.

We studied this in the brain that essentially with brain imaging. So anytime, wherever an expectation of a variable doubts comes and we experience something that is completely different than our expectation we block totally your ability to produce placebo effects. 

Tim Norton: And when you say block, is, is that something measurable, have you seen - 

Luana Colloca:  Yes we measure it in the brain.  We can see which part of the brain can modulate this element of the placebo response. So there are several parts of the brain that [00:28:00] contribute to make people feel better. So somehow a negative expectation or the certain violation of expectancy expectation of something good -  you expect to see something, you expect to experience something, but the reality is completely different than your expectation - creates this sort of a mismatch and then the expectation blocks the ability to experience a placebo response. 

This mechanism that we explore in pain is likely to translate also for sexual dysfunctions, unless there are anatomical problems. I mean, we are talking about patients who can perform, can have an erection. They don't have anatomical [issues] or disease.

So let's talk about the situation where patients are pain-free in our case, they come to the lab, we have them in the scan, we produce a sort of a psychological test [00:29:00] and neurophysiological exploration of the brain changes. And we can see that this migration of expectancy is reflected in the brain parallel from a neurophysiological point of view by changes in specific parts of the brain then they experience no benefit. So again, this mechanism that can be studied and is part of brain functioning probably can be translated in other contexts, including, as you mentioned, patients who can’t have an erection or their expectation is somehow not in line with their experience and this could be. 

Tim Norton: So when that happens from a placebo standpoint, What advice would you give? So, so let's say guy comes [00:30:00] to therapy, let's do it without Viagra comes to therapy and we do 10 sessions of CBT in a row. And he goes, um, to his, his, his girlfriend's house and it's it's sex night, and he has this expectation. And, and it doesn't happen. What, what are some things that we could do even from a laboratory standpoint that might enhance that treatment? 

Luana Colloca: Here I talk based on my experience with placebo research and neurophysiology and not as a therapists that we know that cues are very important.

Tim Norton: Cues.

Luana Colloca: You do the CBT in a room. The patient is with you. You do this 8, 10 sessions of CBT and then the patient goes back to the bedroom. 

Tim Norton: I've got to do the therapy at his bedroom. Okay. 

Luana Colloca: There are many, you know, [00:31:00] consistent cues that trigger something, not to mention the relationship that is so important with the partner.

I mean, we don't know. I mean among the two people, what is there a way to see this moment of intimacy? And again, they may have some different cultural, uh, media and, uh, influences and their expectations can be different. And somehow the way we perceive the other person. That there's another very interesting part of the neurophysiology, even the peri-space around us, you know, can somehow create some positive context, but also  negative triggers that somehow interfere with this complexity of creating an expectation of an outcome and eventual experiencing some other triggers/cues [00:32:00] internally and externally. So when we talk about the final outcome in this case, it’s a complexity of co-factors - within the vision, with the partner and in the context of where they are.

Tim Norton: So I imagine that the cues involving the partner - therapists would be wise to make sure that if we're going to call the partner a “cue” or the other partners gaze, or affect, or how they are carrying themselves cues, that we want to make sure that before the guy goes home and tries this, that, that there isn't something about their partner that is really triggering that, that, that is going to block this response.

We almost have to reshape those cues.  

Luana Colloca: Exactly.  We’re talking about two [00:33:00] people and not just the patient, you know, and it is also important, at least in our experience with being patient, ___________ stories, somehow the history of factors that effect expectations: prior failures stereotypes, example models from the media, TV, show us a little bit like I mentioned - the advertising makes neuropathic trials have larger placebo effects in the States. The same, we are bombarded daily with expectation about sexual performance, sex life. So this can per se affect, you know, this internal combination of their own experience, including the negative experience that, that are dramatic when we talk about placebo effects, [00:34:00] external cues and relationship components are extremely important when we study patients.

I mean, if I try to do a placebo response of someone who doesn't like me, it's better that I leave the room and I let someone on my team talk to that patient.  There are many factors that I would summarize with prior negative failure and experience and the treatment in the patient - external cues, where you are, the context and importantly, the relational cues,  how  there's two people or three, or I don't know how many can interact together and somehow in a way that we don't have a violation of expectations. 

And we know that when it comes to intimacy or sexual life and  [00:35:00] aware of different stereotypes, different expectations, different cultural beliefs, backgrounds that can interfere with this final outcome, because in the brain when we process all this cocktail of cues, eventually this sort of math process that our brain does to predict something can be biased, everybody’s If there is something that's interfering in a negative way. So the trick is to try to understand the words and which factors drive the negative expectation or the violation of expectations.

You want something so badly? You don't do this violation. You never agreed to that That's going to be so relevant.

Tim Norton: Hmm. So I'm thinking about this holistic treatment. And for first of all, this makes me feel much better about doing Zoom therapy, because then they're actually, they can [00:36:00] be in their bedroom. Um, well, while we're talking positively about, uh, positive sexual experiences, so.

It's also made me feel strongly that I should try to have the partner in as often as possible. And then I was already there, but even from a research standpoint, observing what cues may be coming from the partner could be really helpful. Um, and I'm also hearing, I should probably be assigning them a lot of sex-positive videos and TV.

Luana Colloca: I don’t know.  We studied social learning - observing video and TV. Some time observing too much video and TV you are going to create an expectation that can not necessarily match with their want, but something I would ask “what to do you expect?” And try to start from a very beginning where you learn about your patients and [00:37:00] the partners, patients about some of their expectations from where they come from and eventually also where they wants to go. 

Sometimes there is this mismatch of cultural components, beliefs, expectations. Find out if they expect what their partner expects because sometimes it's really, difficult to fulfill the patient's expectation or the partner’s expectation. And show - 

We study social learning in the lab as a main mechanism of a placebo effect.  What is social learning?  People see a video, a patient sees a video of someone else feeling better and they experience relief, no pain. And the way we were wondering what is this, what is happening in the brain, [00:38:00] is this a bias? Again by doing brain imaging we identify some neuronal changes in networks in the brain and the way some parts of the brain communicate.

There's a lot that our prefrontal cortex communicating with some other area of the brain - again, with this part of the brain that is so relevant to create expectations - So when we show something through a video, somehow we impose a model. So it's important to understand that you don't create a mismatch between what they reach and what their expectancy is, and eventually you needed to have some educational tools that match their expectation. Otherwise you may create more factors that will be processed by the brain in a way that's not necessarily good for the patient. 

Tim Norton: You know, I know that to be [00:39:00] true from anecdotal experience, I once was working with a guy with chronic back pain and he was watching this TV show. And there was a scene where somebody, somebody didn't even experience a pain relief, but he called his back pain “psychosomatic” in the show. And, and my, my client had relief for like five, six days after that in a way that he hadn't had in a really long time, just from that show. And I went and I found the show and I recorded it and, and he watched it again and it didn't have the same effect. It was just that one day. 

Luana Colloca: Absolutely, that is a very nice example of a placebo response. When there is this sort of abrupt improvement that we know from a physiological point of view, if you take a medication or if you do something, this improvement occurred even before [00:40:00] we metabolized the medication, even taking a Viagra pill and immediately having the defects, you understand that there's more a placebo effect than on the action of the drug. Eventually, ithis timing doesn't match with the pharmacokinetics of the drug, but this is the power of placebo effects.  People improve. Dramatically. And they can have this sort of improvement lasting for days, weeks, and eventually when they understand that they can do that, you can work the patients to this empowerment and this discovery of their brain’s natural pharmacy this ability to release in the brain something that makes us feel differently, a benefit at any level - pain or sexual dysfunctions. 

But this sort of click, it's not so easy to be produced because as I [00:41:00] mentioned, some patients evolve the ability to somehow trigger this mechanism in the brain. Some other patients we don't know as therapists or physicians how we can somehow get them to do that.

And prior negative experience plays a huge role. What they expect is so important. So I like to somehow frame the placebo phenomenon as a sort of predictive model where prior experience, prior learning, mechanisms,  trauma or positive outcome to consolidation and mechanism in this combination of current expectations that can be dynamically changed can somehow create this anticipation of the next event and we are going to experience placebo effects.

Tim Norton: It really is all about the [00:42:00] expectation. Isn't it? The predicting brain. Did you read Lisa Feldman Barrett's book on emotions? 

Luana Colloca: Yes. I love that book. 

Tim Norton: She really nails it, doesn't she, with the predictions?

Luana Colloca: it is a basic mechanism in our brain and it makes sense. We learn through trials, tests and trials.

Tim Norton: Tests and trials. Yeah, that's what you were saying. 

Luana Colloca: Sometimes the mechanism can go back because it's so pushed in a negative direction and then the less we bring back this ability to reshape expectations, changing mindsets, and the focus on the positive experience.

I mean, once we shift to that level of  brain engagement, this can produce positive [00:43:00] outcomes, but so many there’s a long history of failure.  There is failure with medication, failure with psychotherapies. And negative expectation, rumination, catastrophizing, all creates  the sort of Nocebo.

Tim Norton: NOCEBO, Yeah. And that's kind of, no, CBO is, uh, an expectation that something's not going to work. 

Luana Colloca: Exactly. And we study in the lab why this sort of expectation works so well. It's so difficult sometimes to create a positive expectation, but one word is enough to create a negative expectation and that negative outcome.  You are going to feel a big stick, you are going to feel a huge amount of pain, and telling this information for patients can make him or her feel more pain, even without prior experience of the pain. So if we say [00:44:00] we will feel the pain, but also this anesthetic will numb the area and you will feel much more relief - if we somehow use this framing ability to combine positive and negative components. 

Tim Norton: I like your phrase we have an internal pharmacy. It sounds like we have a really big one. It sounds like we have a much bigger pharmacy than, than a lot of people really give ourselves credit for. The gaps that you guys are experiencing between people who don't respond very well to placebos and the ones that do  - what are the theories that are, is it that some people just don't have very big pharmacies or is there a way to build up those pharmacies? Is it more neurological? Is it more digestive? 

[00:45:00] Luana Colloca: Placebo as we know today is a psychosocial, neurobiological phenomenon is not onlu about brain changes. The brain changes are related to our behaviors. So we have this natural pharmacy, that is the ability of the brain to release endogenous substances.

Unfortunately, we don't have a lot of investigation of this powerful function or the brain. And somehow I feel as scientists that we have been exploring that from a psychological point of view, social point of view, neurophysiological point of view, and that unless we try to integrate this - because our brain is a little different than other organs.

If we talk about a kidney, it’s okay to talk about the physiology of the kidney. But when we talk about [00:46:00] the physiology of the brain, it's much more complex. We can't remember the psychological component and that is what we have been doing for years. Somehow we tended to see some of behaviors as the results of our thoughts and some other things as the result our brain mechanism.  That is not the reality at all, they both go together.

But I think that is coming along with - especially in this area of research where we understand how our expectations that we can frame as a cognitive psychological mechanism - is embedded in brain responses. That is why we we talk about the brain’s natural pharmacy - this ability to expect something while we take a [00:47:00] treatment or we receive some encouraging words, some change in the brain release of endogenous substance from opioids, cannabinoids, what we call endocannabinoid endorphins. Why? Because they belong to the ability of the brain to release substances. 

Tim Norton: a little Latin lesson there for the listeners on a endo happening internally.

What I'm picturing there is, you know, the, the old Cartesian dualism being solved right there. This is, we are mind/body creatures and whatever. One way I've tried to explain this to clients is when you have a thought there actually is a chemical [00:48:00] occurrence that is happening that, and I don't even really understand it. I don't know if, you know, obviously a stressful thought triggers cortisol would be, you know, something, I think I've read a few times and then that's going, the cortisol is going to flow down through your veins and your organs in it. So it's kind of baffling, I think most neuroscientists would understand that.

And most doctors would understand that it's kind of baffling why they've always been so separate when they happen in concert. 

Luana Colloca: Absolutely.  And we know that's consistent level of high cortisol effects many organs in the body, cardiovascular disease, metabolic disease, and so on. So we realize how important it is to still go back to this holistic approach where they will begin as not merely, you know, something that we can't reduce to a value from our, [00:49:00] _______________there is much more than that. 

When we talk about well-being of patients, we need to consider this sort of a balance where, for example when we talk about stress, when we engage in mechanisms that produces stress, - exercise daily life mechanism to relieve stress, so that we can have an impact on metabolic disease, cardiovascular problems, and so on.

I hope that one day, you know, we realize that, eh, the interdisciplinary approach to medicine or psychotherapy is really relevant. 

Tim Norton: And my cardiologist should tell me, sure, take a, take a drug that a lower cholesterol, but if you are stress driving and [00:50:00] have road rage for five hours a day. Yep. They might cancel each other out or that, that, that cortisol drug might not work as well. You might have heart problems. 

Luana Colloca: It is the way we interpret again - we go back to the prediction model. There are many people that conduct a very apparently stressful life, but the way they approach to the routine is enjoyable.  And for them, that kind of life become not too stressful. And you may not even see high levels of cortisol in these kinds of people. Some other people get distressed with much less so the point is the way again, we interpret, we expect, we process events in this beautiful prediction model that is our brain.

Tim Norton: Hmm. That's really helpful because yeah, that, that's the annoying thing for a lot of people. When they see others around them [00:51:00] who are very busy and then they're doing a lot

Luana Colloca: this will influence the way we somehow perceive ourselves because there is this influence and by social media and TV and society imposed some stereotypes that can be not necessarily beneficial.

Tim Norton: Is there a danger in - let's say, let's say this podcast makes it to hundreds of millions of people and everybody, and we become very famous and everybody is just talking about placebos at coffee shops and restaurants.

Luana Colloca: This is happening.  People talk about placebo effects. When we interview patients, they know about placebo sometimes more [00:52:00] than their physician or their therapists. It is a kind of a topic tht is becoming approachable to a wider audiene.

Tim Norton: But you, because even when we're telling people about the effect, it's still effective, you, you don't think that as people learn about it more that it, it will become less effective. 

Luana Colloca: Absolutely not. It is the same way that if you go to your cardiologist and he explains how your heart processes valves, processes the blood.  Even if you learn about how this happens, eventually you can pay more attention to your lifestyle to make sure that you know, you do the things that make you her heart pump better  from exercising, diet and so on. 

So learning [00:53:00] about the placebo is a little bit like learning about the function of any other organs in the body. So the brain is one of the main organs.  Of course we affect our knowledge the way we process things at the level of the brain but the open label placebo where you tell patients this placebo - you can talk openly, there is no need for deception. 

Tim Norton: Okay, good. And one last thing that I wanted to ask you, I think the way I discovered you, you were quoted in this book about honestly, about placebo-style interventions, and you know, it was, uh, there was a chapter on acupuncture. There was a chapter on cults. And I think you said something about allergies. In you, and maybe you, did you tell a personal story though, [00:54:00] that like you, were you able to get rid of your own allergies at some point? 

Luana Colloca: Yes. And yes, I was talking with a reporter and she asked me, did you have any experience with accupuncture? And my experience was that I was having a severe allergic reaction due to some kind of herbs growing in Italy where I come from. In the States, we don't have this kind of plant. 

So I’m allergic, but when I go back, I still have this allergic reaction and the more I am in touch with the allergens, my body responds to it eventually with asthma. And I was using the treatment of steroids, uh, you know, [00:55:00] broncial-dilators, and so on in the classical asthma treatment.

And a colleague of mine, actually an oncologist say Luana - we were having dinner, do you mind if I needle you? I say, what are you talking about? And she's like why don’t you try acupuncture? And I said sure, why not, I don't believe that this kind of thing will works for me, but I was feeling so bad I was not able to exercise, do stairs from asthma.

So she started putting needles and she said you have to stop cortiosteroids for two weeks. I said no I can’t, I can’t breathe, I can’t walk.  She said no, you have to do it.  

Ok fair enough. I trust my colleague physician and I led this acupuncture sessions and after three/four sessions I was feeling much better.

And since then I while I was in Italy, I come back every [00:56:00] June to do my sessions of acupuncture, to treat to my asthma. And I didn't believe that it was going to work. I mean, but I didn't stay on steroids anymore. Mostly because I don't have the exposure to the allergens that are typical there, but I felt like probably was a mix of acupuncture action plus placebo responses and there was an unbelievably high benefit.  I 

Tim Norton: That's, that's great. And we could spend a whole nother hour talking about acupuncture and all the different ways that this effect is playing out. Do you, do you have, do you, is there anything in your life that you do because you know, About placebos that you view any habits that you just make sure that you, [00:57:00] 

Luana Colloca: there are some, I try to use this subconscious, um, paving of cues, you know, like, um, 

Tim Norton: subconscious, what of cues?

Luana Colloca: Like combine things, even if some food, you know, I, I know that if I have some combination I feel better.  

Tim Norton: What would be a combination of food that would make you feel better? 

Luana Colloca: Well I don't like to take a lot of painkillers, but I suffer from migraines and other problems related to pain. And I minimize my intake of painkillers by - if I take a painkiller, I try to pair it with something resilient, like a mint that I swirl in my mouth.  The next time I don’t take Advil or a painkiller  [00:58:00] but take the mint with a vitamin, and somehow I try to trick my brain. Hmm. 

Tim Norton: So Advil plus mint, and then you're teaching your brain that mint is, is a healer, is, is, um, okay. Iike that 

Luana Colloca: So I tried to trick my brain to this association that the mint can trigger the analgesic effects that was related to the true painkiller. So some other examples, if I needed to work - I don't stay caffeine or tea - but seeing or smelling something like caffeine can help me without even taking the caffeine that eventually can interfere with my eight hours of sleep. [00:59:00] So things like that, where I try to use what we study in the lab - learning, associations and teach my body to respond. And there  isn't this question because I know what I'm doing.

Tim Norton:  Yeah. Well, right. There's that. But yeah, you could put out a whole little book or app of just little ways - I like that. The smell of coffee. You do it like right before, did you say work or workout? 

Luana Colloca: Both 

Tim Norton: both. Yeah. A little smell of coffee. Um, cause I know I've noticed before that I perk up 20 minutes before I have coffee.  I'm so excited for that. I'm already very energized and sometimes I, I think I could probably just skip it. I never do though. I always, I always give my body what it's expecting.  

Luana Colloca: patients who are listening to us reframing negative experiences [01:00:00] as learning experiences and see the positive aspects in daily life, or somehow try to avoid this mechanism of avoiding negative expectations where you try to reshape your way to see things in a way that can empower the positive components.

Tim Norton: And that's. You know, I think a lot of self-help people would, would say, okay, yeah, you always have to reframe things, but I love hearing it from you because that's coming from a very well-established scientific researcher and doctor, and that you are absolutely playing to the strengths of your brain's natural ability to heal itself in our very natural pharmacy and when you reframe something like that, and then you're teaching your brain to expect. 

Luana Colloca: Medication sometimes. I mean, myself [01:01:00] is suffering from some form of a chronic pain, there are times that's you need a painkiller.   

Tim Norton: Definitely and sometimes a mint we'll we'll do plenty. All right. Well, thank you so much.  Luana do you have any place on, um, online or where people can follow your work or, or anything you would like to promote? And if you're on social media or anything like that? 

Luana Colloca: Well, we are on social media as the Colloca Lab and also as Luana Colloca. So we try to update our website and Twitter also we used as a tool to make public our scientific results.  So those people would have getting tested to see what we publish, can follow me on Twitter. 

Tim Norton: Okay. Great. So you can follow her on Twitter and her website is the same as her name, which you will see in the notes. Luana Colloca thank you very much for this interview. I really appreciate it.