MR. KOJO NNAMDIFrom WAMU 88.5 at American University in Washington, welcome to "The Kojo Nnamdi Show," connecting your neighborhood with the world. Let's say you got horrible pain in your knee. Your doctor prescribes arthroscopic surgery, preps you, goes through the motions, but doesn't actually perform the surgery. Still, your knee feels much better. Or what if doctors gave you a bottle of pills clearly marked placebo? You take them and your pain goes away. Magic? Maybe not.

MR. KOJO NNAMDIThe long puzzling placebo effect is the subject of new scientific scrutiny and researchers are discovering biological and chemical explanations for how it works. They say the simple expectation of healing can prop the brain to release endorphins that actually help us feel better. The findings could have huge implications for how we deliver medical care, but skeptics say there's a big difference between reducing pain and curing disease. Joining us in studio to talk about this is Wayne Jonas, president and CEO of the Samueli Institute. He's the former director of the Office of Alternative Medicine at the National Institutes of Health. Wayne Jonas, thank you for joining us.

MR. WAYNE JONASMy pleasure.

NNAMDIAnd joining us from studios at Harvard University is Ted Kaptchuk, professor of medicine at the Harvard Medical School and director of the Program in Placebo Studies and Therapeutic Encounter at Beth Israel Deaconess Medical Center at Harvard Medical School. Ted Kaptchuk, thank you for joining us.

MR. TED KAPTCHUKThank you for inviting me. Hi, Wayne.

JONASHey, Ted.

NNAMDIYou can all feel free to join this conversation by calling us at 800-433-8850 or by sending email to kojo@wamu.org. Have you ever experienced the placebo effect knowingly or unknowingly. You can also send us a tweet @kojoshow or email to kojo@wamu.org. Ted Kaptchuk, you studied Chinese medicine and spent two decades as an acupuncturist, though you stopped 20 years ago. How did that experience sparked your interest in Placebo research?

KAPTCHUKWhen I was practicing in China, I watched -- I was trained in socializing and practicing in China. And patients presented certain kinds of complaints. They expected certain kinds of things of me. They evaluated what happened to them after I treated them. And when I came back to the States, I found that patients expected different things from me. They talk differently. They talk about psychological complaints.

KAPTCHUKThey talk about feelings more. They expected different results from the therapy that I gave them. They had different expectations. And what I realized over time is that a significant component of what my practice of acupuncture was or any medical practice is the thick embeddedness that we have when we practice medicine, embeddedness in culture and expectations and a narrative of what people expect and experience from that encounter.

KAPTCHUKAnd at some point, when I was invited to join the faculty at Harvard Medical School and they asked to research medicine, I sort of switched over and said, I'd like to look at -- because I kept saying, well, it's all about -- they think that acupuncture is a placebo effect. And I said, so what is that? And when I got very brief and not clear answers, I said maybe it's more important to study the placebo effect in Chinese medicine for me as a researcher. And I switched careers at that point.

NNAMDIWayne Jonas, you're a family practice physician and you still see patients at Walter Reed National Military Medical Center. How did you get interested in the placebo effect and the way that it plays out in medicine?

JONASWell, as a practicing physician in the military for over 20 years, I always thought that what I did was producing the healing. And then when I began to look into the research in the area and discovered that actually there were a lot of other things separate from what I thought was producing the healing, the chemical or the drug or the surgery. And it was actually stimulating it. That got me more interested in the art of medicine and how the context and the communication and the delivery components of what I was doing were contributing to that healing. So, as a researcher then, I began investigating that area and started to dig into that black box.

NNAMDILet's start with some definitions. I know there's some confusion about the terms placebo and placebo effect. Can you define them both for us?

JONASWell, the word placebo is most often used to refer to, and a treatment, usually a pill that companies or drug study where the chemical component of the drug is not part of the pill. And so, that's often used as a placebo, is called the placebo. And it's used to try to separate what is sometimes then called the placebo effect, which is the response from having given in our treatment with all the bells and whistles of a normal treatment. So those are the general conceptions.

NNAMDITed, what role -- and I'd like to hear your definitions also, Ted, if you're willing to.

KAPTCHUKOh, I'm a very compliant guest. I think that the placebo pill is just a sugar pill. And it's the -- and we think sometimes that that's what we're talking about. But in fact, the pill is embedded in an elaborate context. It's embedded in the act of just caring. It's embedded in medical rituals and symbols. It's embedded in doctor-patient relationship. It's carrying a lot of imagination, trust and hope. And all those factors are what I would call the placebo effect. And to do it more elegantly, I would say that the placebo effect is the outcome of the therapeutic imagination and the body's intelligence. So it's my definition.

NNAMDIWhen you say the therapeutic imagination, what role do a patient's expectations play in how well he or she responds to a drug or a treatment, whether it's a placebo or not?

KAPTCHUKI'll start, Wayne, then please take over for me. I think that expectations is one of the psychological models that researchers have for explaining placebo effects. Some people think that placebo effects are exclusive expectations. I think that expectations -- at this point, I think the evidence is that expectation plays a role in some situations. But I think things like meaning, conditioning also play a role in the psychological level -- projection of anxiety, feeling comfortable play a role. Expectation is not, I think, the exclusive mechanism involved in most placebo effects.

NNAMDIWayne Jonas?

JONASYes. I think expectations clearly are one component of this black box we call placebo. People often believe that by expectations you mean you have to somehow consciously believe in the effect and that, therefore, that's what's producing a sort of a mind over matter type of thing. And yet it's a lot more complicated than that. The things that generate our own expectancies have to do with the rituals that we go through, the number of pills we take, the location in which we actually take the pill or receive the shot.

JONASThe message that the physician gives along with it, whether it's positive or negative, and what the culture believes about -- you know, in our culture, often higher priced things are thought to be more valuable. And if you put a higher price on a medication, it generally has a bigger effect.

NNAMDIGive us some examples of studies that demonstrate the strength of the placebo effect. Talk about arthroscopic surgery for knee pain.

JONASWell, I can do that, Ted, if you don't mind. I'll start with that.

KAPTCHUKWell, I was hoping you'd start.

JONASSo one of the first studies really trying to disentangle in a surgical procedure like arthroscopic surgery, where a person has arthritis of the knee, for example, and they stick a scope into the knee was done by Dr. Moseley. And at the NIH back in 1989 we featured his pilot study and he subsequently followed it up with a larger study in which he then did the arthroscopic surgery or he simply washed the knee out, didn't actually do the surgery or simply made a cut over the knee as if the surgery was done, didn't even stick the scope in.

JONASAnd he followed patients for their function and their pain for over two years and showed that if you simply went through the ritual of talking to your surgeon, getting prepared for surgery and have a little cut over your knee, your pain was relieved to the same extent that doing the surgery produced. And that was a real eye opener for the community and other studies since then that have sort of verified that type of approach.

NNAMDIWe're talking about the future of placebos in medical care. I'm taking your calls at 800-433-8850. Wayne Jonas is president and CEO of the Samueli Institute. He's a former director of the Office of Alternative Medicine at the National Institutes of Health. He joins us in studio. Joining us from studios of Harvard University is Ted Kaptchuk. He's a professor of medicine at Harvard Medical School and director of the Program in Placebo Studies and Therapeutic Encounter at Beth Israel Deaconess Medical Center at Harvard Medical School.

NNAMDI800-433-8850. Do you think the way your doctor talks to you and his or her optimism about your treatment affects your recovery? Call us, 800-433-8850. Ted Kaptchuk, one of the big concerns of placebo research is the role of deception. Does the placebo effect only work if patients believe they're taking a real drug? You've looked at what happens if you remove the deception and tell people they're getting a placebo. What did you find?

KAPTCHUKWell, one of the conventional wisdoms in the medical community has been that you -- in order for a placebo to work, there has to be deception or concealment. The patient has to think there's a possibility or think that they're receiving the active therapy. As a person who does a lot of placebo research, I saw that -- it's clear to me that if we're ever going to move placebo studies into clinical arena that we have to figure out ways of using placebos or placebo effects without deception.

KAPTCHUKAnd our team took a chance and we decided to, based on -- there's a lot of qualitative studies we have done and we decided to randomize 80 people with irritable bowel syndrome either to open label placebo, that was we told them that we're giving them placebo and told them it was microcrystalline cellulose inside. The bottle said placebo. When they called up and told them it's a bottle of placebos, we randomize them to three weeks 40 people with irritable bowel for three weeks to receive placebos or half of them, another 40 people were randomized to just white list control, no treatment so we can see if the improvement was really in placebo effect or it's just waxing and waning the natural fluctuations of disease.

KAPTCHUKAnd we found that in fact the people on placebo did significantly better, as good as any drug has ever been tested for irritable bowel and they had no problem recruiting them. And they had a very pleasant experience and many of them asked, where can we get more? Our study was very small. It was -- we consider it a pilot study, but it puts on the table the concept of can we use placebos openly with full consent and transparency with patients.

KAPTCHUKAnd, of course, our team, and I hope other teams are going to try to pursue this line of investigation to verify whether it's true or not, to find out how long it lasts and what illnesses it can apply or not apply to. We actually have two studies in two other diseases ongoing that we'll finish very soon, whether this strategy has any possibility of actually becoming something to consider therapeutic.

NNAMDIAnd, Wayne Jonas, how do you explain the fact that people seem to think more is better when it comes to medicine? In studies of placebos, people reported that two pills made them feel better than one and that the color of the pill had an impact on how well it work even when all the pills were sugar candies.

JONASYes. The number of times you take the pill, the location that you take it in, who gives it to you, the message that Ted just referred and the ritual they take, almost converge into producing what we call this expectation. Although as we said, it's not entirely expectation and there's other factors, but these healing effects, these effects that stimulate healing. Every physician sort of knows this. They use this every day in their practice.

JONASAn example of the communication is that study done by KB Thomas a number of years ago showed that you simply give a positive message with your treatment, you can markedly improve the likelihood that people will feel better and that their primary condition will go away, given certain kinds of conditions obviously that are more responsive to that. KB Thomas, back in 1987, published a study in which simply telling doctors to give a positive message along with a pill, such as I think this is going to work for you, if you have any more problems, let me know, compared to a negative message, where they said, well, I don't know what you have and I'm not sure if it's going to work, that simple communication device would increase the responsiveness from 40 percent to 60 percent almost an additional third on top of that.

JONASSo simple types of things can converge to make those -- if you put them altogether, you could probably create an optimal healing environment and delivery system.

NNAMDIGotta take a short break. When we come back, we will continue our conversation on the future of placebos in medical care. Have you ever wondered if your doctor was giving you a medication that was intended to calm your fears more than to cure your condition? And how did that work for you? 800-433-8850. Go to our website, kojoshow.org, send us a tweet @kojoshow or email to kojo@wamu.org. I'm Kojo Nnamdi.

NNAMDIWe're talking placebos and the future of placebos in medical care with Ted Kaptchuk, professor of medicine at Harvard Medical School and director of the program in placebo studies and therapeutic encounter at Beth Israel Deaconess Medical Center at Harvard Medical School. And Wayne Jonas, president and CEO of the Samueli Institute, he's a former Director of the Office of Alternative Medicine at the National Institutes of Health. I'd like to go directly to the phones. Here is Lisa in Leesburg, Va. Lisa, you're on the air. Go ahead, please.

LISAHi, yes, I was an athlete and then a mom and spent a lot of time with people who've been injured and, you know, were hurt or sick or whatever, and have had to just, you know, dispense regular helpful advice and things that have worked for me. And the thing that I noticed that I absolutely believe in the placebo effect, is that if you are absolutely convinced that this has worked for you, and they believe it, then it's gonna work for them. But what I notice is really what it gives people is they seem to sleep better, and they rest better, and when I had back surgery, I was told by my back surgeon that you heal while you're sleeping, so the most important thing you do – one of the most important components of an effective recuperation or even an effective procedure, is your ability to rest.

LISAAnd I'm wondering if there's been any study about how the placebo effect particularly is effective either through rest or if it affects rest in any way.

NNAMDIYou've got me wondering the same thing. Let's ask Ted Kaptchuk.

KAPTCHUKWell, I think it's very interesting. I think that anxiety reduction is a significant component of the placebo effect, and I think that reducing anxiety has – cascades into a whole bunch of other effects, like being more relaxed, being able to sleep better, being less tense, which would lead to benefits that you're describing. So I think what you've seen is, from my perspective, an accurate description of what's possible.

NNAMDIThank you very much for your call, Lisa. I was surprised to read that a recent survey of internists and rheumatologists in the U.S. found that half of them prescribed medications they don’t think have any specific effect on a patient's condition. The doctors used these solely as placebos. What do you think of those numbers and that practice, Wayne Jonas?

JONASWell, when I was starting in medical school over 30 years ago, they had in the pharmacy something called placebo spelled backward, which you could write a prescription for if you wanted to actually give a placebo, and the pharmacist would know that they could give a sugar pill, write the indication on it. Now that's gone out of favor nowadays, so that's no longer felt to be ethical to do that. And yet, physicians need ways of delivering treatments in some way to indicate that they're helping the patient in some way, and so now, the placebos tend to have some kind of active ingredient in it, even if it doesn't work for the specific condition they're doing.

JONASSo, for example, most physicians nowadays in that survey that you mentioned would prescribe antibiotics even when they knew it was a virus and not effective, or a vitamin pill, even when there was no evidence that it was going to benefit them specifically.

NNAMDISo that's an example of how placebos are used today, as opposed to simply writing the word backward.

JONASThat's correct. (laugh)

NNAMDITed, one of your goals is to use rigorous scientific research to examine the placebo effect, and that means looking at the biology of what happens. What's the relationship between endorphins and the placebo effect?

JONASWell, in 1978, Gordon Levine published in The Lancet an eye-opening article where they were able – they had patients that had placebo responses and then they gave them Naloxone, which is an antagonist for endogenous opioids, and it blocks the receptors, and what they found was that if a person was injected with a Naloxone, they didn't get a placebo pain relief, and – the implication, the inference was that the placebo effect was in some way directly related to the body's release of endogenous opioid-like substances that relieve pain. That study has been confirmed many times.

JONASAnd subsequently, many other neurotransmitters have been linked to placebo effects. For example, in 2008, de la Fuente in Science demonstrated that Parkinson's patients, when they were injected with saline solution, which they thought was a real drug for Parkinson's disease, a dopamine-like drug, the striatum of the brain released a significant amount of dopamine that had the same curative effects as if they would have gotten an injection of dopamine. Meaning that that's been implicated. Very, very recently a team in Italy, (unintelligible) team in Nature Medicine demonstrated that CP1 cannabinoids are implicated in some kinds of placebo responses.

JONASSo we're getting the development of a rich cornucopia of neurotransmitters that are linked with, and are implicated in placebo effects, at the same time, there's been a blossoming of neuroscience studies of placebo effects, and there have been over a dozen that have clearly demonstrated that certain areas of the brain, like the anterior insula or the rustle anterior cingulated, which modulate perceptions of sensations and bridge cognition and sensations, are activated during times when people are given placebos and get a placebo response. So there's a neurotransmitter biology behind it.

JONASI think that this kind of neuroscientific neurobiology has given placebo researchers who do clinical research more confidence that is this real, or is this just the imagination? Well, it may be the imagination, but it also has a biological correlate, and I think there's a lot more research that needs to go on here, because the more we understand the mechanism, the more we'll be able to hopefully translate that into strategies and techniques it the clinical situations.

NNAMDIAnd so neuroimaging expands our ability to understand this phenomenon?

JONASYes.

NNAMDIOK, on to Marilyn in Fairfax, Va. Marilyn, you're on the air, go ahead please.

MARILYNHi, Kojo, thank you. I have been a chiropractor for over 30 years, I work with Joe Jacobs, before Wayne was in OAM, he headed it up and did a number of panels together. And I'm kind of curious because one of the things that the medical profession held out as a negative side of chiropractic is their claim that chiropractic is a placebo. And I'm not hearing any of the research dealing with any of the physical sides of medicine, either physical therapy, chiropractic, physiatry, any types of manipulations. And I’m wondering if there's any research going in that direction, or if it's only sticking with chemicals or possibly, in Ted's case, the effect of acupuncture?

NNAMDIWell, indeed...

MARILYNOr anything with either hands on, and I love the fact that, you know, you're talking about hands on healing, and the body's innate intelligence, which is what it's called in chiropractic, but the fact that the body knows how to heal itself, which has been a premise in chiropractic all along, and I've never heard that come from a medical profession, so it's kind of nice to hear that.

NNAMDIWell, Marilyn, you're right about one thing, as head of the NIH's Office of Alternative Medicine, Wayne Jonas heard a lot of people dismiss things like homeopathy or chiropractic treatments, as the placebo effect. Do we know enough about how homeopathy works or chiropractic works to agree or disagree?

JONASWell, one of the first meetings that we had at the NIH when I ran the Office of Alternative Medicine was to look at the role of placebo in what's called complementary and alternative medicine, like acupuncture, chiropractic, as Marilyn is talking about, herbs and this type of thing. Many of those types of therapies have evolved out of cultures over hundreds, even thousands of years, back before we had science that could dissect the specific effects that were going on. And so it's logical to assume that they made use of the art of medicine, and developed rituals for delivering healing that maximized some of these components that we're talking about in terms of expectation and delivery and ritual and that type of thing.

JONASSo we were very interested in what contribution those types of things had in facilitating healing and stimulating those areas. And so it became an area that the NIH and the subsequent, after the Office of Alternative Medicine, the National Complimentary Medicine Center that exists now, has funded studies in those areas to try to understand how those therapies actually do produce these kinds of innate healing processes.

NNAMDIMarilyn, thank you very much for your call. We move on to Daphne in Kensington, Md. Daphne, you're on the air, go ahead please.

DAPHNEHi, thank you so much, and I'm so glad to be speaking after Marilyn, because she mentioned hands on healing, and that's the kind of work that I do as well. And what I've discovered, I have a lot of clients come to me, I do something called Healing Touch and somatic experiencing. They come to me with issues like depression, anxiety, I have a lot of clients who come because they can't breathe, and they've had all the medical tests and all the drugs and everything, and the anxiety is still there. And so I started looking into these medicines, because I thought, you know, they've come to hands on healing, which is not covered by insurance, you know, at last, when they've tried everything else.

DAPHNEAnd I started looking at these antidepressants and anti-anxiety medicines, and they perform barely better than placebo. I'm sure your guests can talk about that. So my question is, why is the American Medical Association so opposed to using placebo, or placebo spelled backwards, as Wayne said, you know, as a first line of defense, because so many of the conditions in our culture right now are stress related. So why don't we use placebo first, doctors, and also encourage them to use other kinds of healing, and if that doesn’t work, then give them the powerful drugs which have so many powerful side effects, like weight gain, diabetes, etcetera?

NNAMDITed Kaptchuk?

KAPTCHUKWell, it's a really good question. First of all, you have to remember, the placebo effect was really, the placebo control was invented as a way of establishing legitimacy and authenticity. A drug had to be more than a placebo effect in order to be a real drug, whether it had a big effect or a small effect. So there's a kind of attribution that a placebo effect is really bad. The AMA's rule, code of conduct 206, does not say you can't use a placebo effect, you can't use a placebo – you can't use a placebo, it says that you can't use it deceptively. And in fact, if you use it transparently, I see no ethical reason not to do it, as long as you have informed consent.

KAPTCHUKIt does – the AMA's code of conduct does suggest that doctors use an enhanced doctor/patient relationship to build on something that might be called a placebo effect, so I think that I agree with you that it would be nicer to use more benign methods of healing before we use more potentially – forms of healing that have more side effects, but I think ultimately the question is for any situation, is what's the risk benefits of using whatever intervention you're doing. How effective is this therapy going to be, and what are the risks that it involve, what's the outcome of this illness without this kind of intervention.

KAPTCHUKSo it's a complex question, but I think that the research being done in placebo studies is about how do we foreground what has been in the background? The act of caring, the act of – the doctor/patient, doctor/practitioner encounter, how do we use that more prominently, more effectively, more optimally? So that's where I think it's going.

NNAMDIThank you very much for your call, Daphne, I'm glad that Ted Kaptchuk brought that up, Wayne Jonas, so you can talk about what you call the meaning response. How do patients attach meaning to things like a doctor's manner, and doctor's language, even the white coat? And how do these meanings affect the outcome of the treatment?

JONASI think ultimately, all these components in this black box we call placebo are transmitted through meaning, both consciously and unconsciously. The culture sets up those expectations, we learn them from when we're little, and the authority of the practitioner then adds on to that, delivers and changes the expectation, then the ritual of the treatment itself conditions, and your body actually learns how to respond to that, and there's some fascinating studies showing that you can teach the immune system how to change, up and down, simply by attaching a ritual, such as a smell or a taste, to a drug, then removing the drug, giving the smell and the taste, and producing the immune modulation that you would get with the drug.

JONASSo that's called conditioning, and learning, that is. So those kinds of things are the components. And I think if we understood those and we taught doctors how to combine them optimally, we could, you know, do away with deception. We wouldn't need to do away with deception. But there's another reason that's it's important to study these rigorously, to answer Daphne's question, also, besides deception. And that is, frequently, if the ritual is producing most of the effect, then the question is, why don't you just teach people how to do that.

JONASOne of our investigators, Shaminy Jane (sp?), studied the exact type of hands-on healing that she mentioned to look at its effect in cancer patients' fatigue, the fatigue that follows a lot of cancer treatments, and showed the hands-on healing produced significant improvements, but so did a sham procedure, just waving the hands in a similar way, people got significantly better in those areas. And so how should we deal with that? Should we pay for that? Do we need to train people in it? What are the costs of doing that?

JONASHow should the system deliver it? And can a physician just incorporate those types of rituals and hands-on healing as a key component? Every physician knows that if you touch the patient, that often has a therapeutic effect and so simply incorporating that into normal healthcare and medical care would be one of the ways you could incorporate this knowledge into medicine.

KAPTCHUKCould I...

NNAMDIPlease go ahead.

KAPTCHUK...add to Wayne's comment? Because I really like what Wayne just said. And one of the things that strikes me is that we're talking about how to incorporate this, quote, "placebo effect," but, in fact, it's there all the time and the real question is how to optimalize (sic) it. Well, physicians touch their patients. They encourage their patients. They attentively listen, ask, what did you say. They think hard. They work really hard to take care of their patients, in most cases.

KAPTCHUKAnd what it is, is I think that just making -- bringing what this kind of normal behavior that we have in healthcare, making it more self aware for the physicians, patients are demanding it and trying to figure out how to optimize it is what we're talking about in terms of placebo studies. Because when Wayne said physicians do touch, but, you know, knowing that touch is important probably charges that touch a little bit more. It would be interesting to do an experiment like that and see if that's true. But I just wanted to say that.

JONASAnd this is embedded in all therapies, complimentary therapies, conventional therapies and so we should be teaching all practitioners about those components.

NNAMDIAnd how early does this conditioning start? Let's go to Jim in Baltimore, Md. Jim, you're on the air. Go ahead, please.

JIMHi. Thanks for taking my call. Like, my question is, you know, when we were small and we fell down and we brought our skinned-up knee to our mom and she said, I'll kiss it and I'll make it better, and that was the placebo effect from very early on. And as we developed, we seem to need to be -- our minds have -- everything has become -- the faith out of everything is taken out, and so we need something that has a side effect to make us better, and is there a -- when we had the placebo effect, do the cells actually go to that injury or that illness to combat it or back it better, to heal, or...

NNAMDIWell, that's one of the things we're discussing right now, the extent to which one assists and the other assists and trying to figure out exactly how much of one and how much of the other. But Ted Kaptchuk, is Jim, in fact, correct? Is that when the therapeutic encounters begin?

KAPTCHUKWith the mom kissing the boo-boo?

NNAMDIYes.

KAPTCHUKAbsolutely. I think so.

NNAMDIYeah.

KAPTCHUKAnd I think the caller asked another interesting question. If you treat -- does the placebo effect affect one particular area of the body versus the whole body? And there are two or three experiments on this, so it's still premature to make a clear inference, but some studies have shown that if you treat one knee with -- or one elbow with a placebo cream and not the other elbow, and both elbows had pain, that it actually selectively affects the one that you're treating. And that's a complicated question because endorphins are centrally released. And how does it work in the periphery? I think we still don't know.

KAPTCHUKSo it's a really complicated -- a lot of complicated questions still there, but bottom line, I think kissing boo-boos is an important part of who we are as people.

JONASI would just add to that, and to answer Jim's question, is that you don't have to be conscious of this to actually produce the effect. The kissing the boo-boo aspect of it is a learned condition response that we talked about before, and that has been clearly demonstrated in research in animals where you simply teach the animal to respond to a particular signal or ritual or a touch, et cetera, and then their body responds to that even down to the cellular level, even down to the different receptors that turn on and turn off, sometimes in a positive way as we've talked about to relieve pain, but also sometimes in a negative way.

JONASYou can have a communication or a condition that can increase your sensitivity to pain and increase pain, so you have to be careful with the message that's delivered.

NNAMDIGot to take a short break, but we will be continuing our conversation on the future of placebos in medical care. If the phone lines are busy, send us a tweet @kojoshow with your question or comments, email to kojo@wamu.org. Given the biological evidence supporting the placebo effect, do you think there's ever a case to be made for giving a patient a placebo and not telling him or her? 800-433-8850. I'm Kojo Nnamdi.

NNAMDIWelcome back. We're talking with Ted Kaptchuk. He's a professor of medicine at Harvard Medical School, and director of the Program in Placebo Studies and Therapeutic Encounter at Beth Israel Deaconess Medical Center at Harvard Medical School. Wayne Jonas is president and CEO of the Samueli Institute. He's a former director of the Office of Alternative Medicine at the National Institutes of Health.

NNAMDIWhat goes on in our brains when we listen to a doctor talking about the pain we have and the treatment he or she recommends? How do the very words that the doctor uses activate different parts of our brain, Wayne Jonas?

JONASWell, I think there are different parts of the brain that are responsible for dealing with different types of signals, physical signals for example, and there are other parts of the brain that deal with emotions and the anxiety, and there are other parts that deal with movement and interaction with the immune system. So for example, if you were to stick a needle in a person's hand, you would light up parts of the brain that feel the needle and register the pain.

JONASIf the person was anxious about it, then the emotional part might light up. If you were then to, however, a person with pain, stick the needle, tell them that it's a therapy, let's say it's an acupuncture therapy, stick the needle in the same point, you'd light up all those same physical areas in the brain that register the needle, but you'd also light up areas of the brain that begin to turn on pain therapeutic effect where the endogenous opioids and these other kinds of pain killers in the brain get turned on that are not turned on if you simply stick the needle in by itself. So the words then turn on different parts of the brain, interact with the needle in a way that induces the pain relieving effect.

NNAMDIWe got an email from Michael, Ted Kaptchuk. "Are particular types of people known to benefit from placebo treatments? Is it like hypnosis where a few people are easily hypnotized, a few are resistant to it, and the majority somewhat susceptible to hypnotic suggestion? Putting my question another way, are gullible, open or trusting people more likely to benefit from placebos than skeptical, rigid or hard-headed people?"

KAPTCHUKRight now, there's no consensus in the data looking at is there someone that's more prone to respond to placebo versus less prone to respond to placebo treatment, is equivocal. And I think there's methodological problems. Our team is working very hard to -- because we have a lot of blood of people who have responded and not responded to placebo looking for genetic and other biological markers for responding to placebo.

KAPTCHUKBut right now, I think we can't say there is someone that's typically a placebo responder. People have -- and in terms of hypnotizability, there isn't an overlap between people who are hypnotizable and respond to placebo in the studies that have done that. Suggestibility scales have not predicted placebo responders consistently either. So right now, we're still at a mystery point on that question in my opinion. I'll defer to Wayne if he has another opinion on the data.

JONASI think that's right. I think we don't know exactly. There's clearly people that respond to the ritual to the components of this placebo effect more vigorously than those that don't, but we haven't really figured out exactly are there certain characteristics, and it's probably a combination of different things, prior learning experience, anxiety, perhaps some genetic effects as well as some of the receptivity issues and the environment that they're in.

NNAMDIWayne, how do you separate the benefits of healing from the benefits of curing a disease? Can one exist without the other?

JONASAbsolutely. Healing and curing are sort of interlaced and overlapping, but not the same. Everyone knows someone who has been cured of their disease but they're not healed. They continue to suffer from that, and we know individuals even at the end of life that can feel healed, be whole, come to a resolution even though their disease can't be healed. So they intersect with each other inducing and maximizing the healing responses using some of the components that we've been talking about in the placebo effect can enhance those healing responses, and sometimes that results in a cure of a disease, and sometimes it doesn't.

JONASBut it always can, if properly used, result in improved well being, improved function, and relief of pain and suffering.

NNAMDITed Kaptchuk.

KAPTCHUKKojo...

NNAMDIGo ahead, please.

KAPTCHUK...could I add to that a drop?

NNAMDIPlease do.

KAPTCHUKWe published a study in the New England Journal this summer that addressed that question very directly. We gave 40 people with asthma. We took them off the drugs 12 different times. Each patient was treated 12 different times, and of those 12 times, three of them with a bronchial dilator, a regular drug. Three of the times were fake bronchial dilator, three of those times was fake acupuncture, and three of those times they just sat there for two-and-a-half hours, and we wanted to see if just sitting there and doing nothing would make them better anyway.

KAPTCHUKAnd we found that when we measured the air in the lungs, how much expiration they were -- actually was expired, a biological measurement, that the real medication, the real bronchial dilator significantly improved their condition. The placebo Albuterol, the placebo inhalator and the placebo acupuncture improved their breathing a little bit, but also, just sitting there and doing nothing improved their asthma just a little bit.

KAPTCHUKAnd in fact, there was no placebo effect because there was no difference between the fake inhalator, the fake acupuncture, and the fake -- and just sitting. We actually didn't have a placebo effect. We were very saddened that all that work didn't lead anywhere, and luckily I said pull out the subjective outcomes immediately. And our statistician crunched those numbers quickly and what we found was very interesting.

KAPTCHUKWhen we asked patients how much they feel better, how much did they feel their lungs improved in each one of these 12 sessions, the Albuterol, the real drug, the bronchial dilator made them feel much better. The fake inhalator made them feel much better equally. The fake acupuncture made them feel much better equally and the no treatment, just sitting there, didn't make them feel better. And in fact, there was no difference between the real drug and the two different placebos.

KAPTCHUKThere was no drug effect when you measuring people's experience, how they felt. And what we concluded, at least in this particular condition and this particular model that the placebo doesn't necessarily change underlying biology, but can have a very big positive effect on how a person feels. Whether that's true of other conditions, I can't say, and I think that sometimes just feeling better, I'm not sure if it's true of asthma, but say if you feel better about your knees, just walking may reduce inflammation. But there is a disjunct between to what extent placebo, ritual, symbols affects real biology, and to what extend placebos, rituals, and symbols affects the experience of illness.

KAPTCHUKDoes it cure or does it make you feel better and heal? Sometimes they don't, as Wayne said, those two concepts don't necessarily overlap. Both of them are very important, I think, when people go to doctors, go to practitioners and ask for help.

NNAMDIWayne?

JONASI'd just like to add. I take a little bit of issue with you here, Ted. I think...

KAPTCHUKOh, good.

KAPTCHUKI think that the disjunct is because the field is so new in understanding what these components are, that we really don't know where the boundaries are and where the barrier is between what these kinds of ritual and healing effects can produce. And so I think it's premature to say that it doesn't have an effect on real biology. I think there's emerging evidence that indicates that it could have effect on real biology immune system, healing of physical ulcers, this type of thing. And I think we just haven't done the research to try to find out how those parameters can be impacted by these approaches.

NNAMDIWhat does the term...

KAPTCHUKI'll take that criticism positively. I think it's correct. Thank you.

NNAMDIWhat does the term nocebo refer to and how does it factor into your research, Ted?

KAPTCHUKNocebo, the word comes from, in a clinical trial, when you're comparing an active intervention, a drug or -- a drug, for example, with a placebo, you have a placebo effect. Some people get better anyways. But what's also true is that many people who are taking the placebo have a negative effect. They get the nausea, they get the vomiting, they get the dizziness, they get the headaches that the real drug causes, but they're on sugar pills. That's called the nocebo effect.

KAPTCHUKSo there is actually the rituals that we perform, the doctor-patient relationship sometimes can be very positive, and sometimes it's possible, clearly from the evidence we have in randomized controlled trials, that can make you worse in the same way that I suppose healers in earlier preliterate cultures were always -- people went to them to get cured and get healed, but they were also leery, maybe they're going to do something bad. So I think that we have to be careful we're not only studying something benign, and if something's only benign, it probably doesn't have much effect anyways.

NNAMDIOnto the telephones. Here now is Jack in Columbia Heights in Washington. Jack, you're on the air. Go ahead, please. Hi Jack, are you there? Well, Jack -- we seem to have lost Jack for a second so I will move on then to Henry. Uh-oh, Jack, you're gonna have to call us back. I think I just cut you off. Here now is Henry in Annapolis, Md. Henry, you're on the air. Go ahead, please.

HENRYHey. Okay. So I have a great story for you guys. In fact, you guys have been awesome the last two days. I've been like, oh, I need to call in. Like the Tebow thing, I was like, gotta call, and then yesterday with the band that you had in, I just released an album digitally and I was like, oh, I gotta call. And then today, I was like, that's it, I'm calling.

NNAMDIYesterday, Fugazi, the day before Tim Tebow. But go ahead, please.

HENRYOkay, yeah. So this has to do with just like how, like, touch can heal. I was meditating one day and my wife came in and she was like, oh, my upper back hurts, can you come rub my shoulders? And I was like, sure, okay. So I go over and I'm, you know, I'm in this just like, you know, I've been meditating for a while and I'm just very in tune with myself. And she lies down and I see over her sciatic nerve this red dot, and, I mean, I feel like this is something like what reiki is. I don't know, though. I've never done reiki.

HENRYI know somebody who did it, but I didn't really talk to him about it. But I saw this dot and I was intrigued and I was like, wow, okay, so I just like started kind of like poking and prodding at it, and this red dot became bigger over her sciatic nerve. And she was like, I don't know what you're doing, but that's -- like, it's tickling and it kind of makes me feel uncomfortable. And I was like oh, well, sorry, and the dot got bigger. And then I was like, well, maybe I can try to make this thing go away. Maybe this is...

NNAMDIWe're running out of time very quickly, did it work?

HENRYYes. I made it go away and I didn't even touch her upper back. But she said that I fixed whatever was going on with her upper back and I didn't even touch it. It was her sciatic nerve that was bothering her.

NNAMDII don't know. Is there any explanation that you can offer for that, Wayne Jonas?

JONASWell, I think the point Henry touched on at the beginning is that this is not just isolated expectation of an individual, that there is indeed a duo that goes on when two people interact and their belief interchanges. And we're buried within a culture, and the culture has certain beliefs and expectations, and so when the culture believes in a certain thing, perhaps money or astrology, then if you're delivering something with those components as a major aspect then you'll get greater effects.

JONASDrug companies know this. That's why they brand and try to brand their medications. A great study done in Switzerland several years ago has shown that aspirin works for headaches, but if you brand it Bayer aspirin that you'll get an even better effect. And so the label and what the culture believes influence the individual responses of healing in this area.

NNAMDIHenry, thank you very much for your call. Ted, we only have about 30 seconds left, but your team is looking now at whether the genes of people who respond well to placebos are different from those of people who don't. What prompted you to ask that question and what are you learning, in 30 seconds or less?

KAPTCHUKWe still -- we are furiously trying to complete the study. We just have hypothesis that may be possible if there's a certain kind of genetic profile that would be more prone to a placebo response. We have a lot of blood so we're trying it, and the NIH funded us to do it, and (unintelligible) funded us to do that, so we're hopeful. We'll see what happens.

NNAMDITed Kaptchuk is a professor of medicine at Harvard Medical School and director of the Program in Placebo Studies and Therapeutic Encounter at Beth Israel Deaconess Medical Center at Harvard Medical School. Wayne Jonas is president and CEO of the Samueli Institute. The Samueli Institute is hosting a two-day conference on placebo research later this month on January 19 and the 20th. That will be a professional meeting, but the public is invited to a discussion on healing at placebos at the Italian Embassy on the 20th of January at 6:00 p.m. We've got a link on our website, kojoshow.org for more information.

NNAMDIWayne Jonas is former director of the Office of Alternative Medicine at the National Institutes of Health. Thank you both for joining us, and thank you all for listening. I'm Kojo Nnamdi.