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This is TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.

The placebo effect - you know what that means - that means it's an improvement some patients feel because they believe, they believe they're getting medicine even though they've been given a sugar pill and not a real drug. What's mysterious about the placebo effect, though, is that if those patients believe that sugar pill is working, it may actually begin doing something for them.

In fact, the placebo effect has been on, and I think something like 30 percent of placebo seemed to work all the time. But even though every single clinical trial, as always, you know, takes the placebo effect into account, no one knows exactly or no one knew exactly how it worked until now.

Dr. Tor Wager and his team have come up with some answers. Dr. Wager is assistant professor of psychology at Columbia University here in New York. He's here with us in our New York studios. Welcome to SCIENCE FRIDAY.

Dr. TOR WAGER (Assistant Professor of Psychology, Columbia University): Well, thank you. It's a pleasure to be here.

FLATOW: Now you actually looked - fascinating experiment. You actually scanned people's brains and you gave them a placebo and watched what happened. Would that be fair?

Dr. WAGER: Fair enough.

FLATOW: Little more detailed than that.

Dr. WAGER: Right.

FLATOW: Tell us the facts - tell us what you did.

Dr. WAGER: Okay, sure. Well, you know, this started - I've had a long-standing interest in mind-body connections and whether, sort of, you know, your beliefs and expectations can actually influence things in your body. And it's really only been recently with the advent of neuro-imaging techniques like functional magnetic resonance imaging, positron emission tomography. These are techniques that we can use now to scan a living human brain as they are experiencing different things.

FLATOW: And you watched they light up on the scan.

Dr. WAGER: People like to say that the brain lights up in different aspects.

(Soundbite of laughter)

Dr. WAGER: Increases in activity in different areas of the brain and, you know, different patterns of activity in the brain are associated with different things. So, for example, we're studying placebo effects in pain in my laboratory among other things. And if I give you a painful thermal stimulus -something that gets hot - like if you grab a really hot cup of coffee, for example...

FLATOW: Right, right.

Dr. WAGER: ...there are particular areas of the brain whose activity increases, and we can see that in the MRI scan.

FLATOW: Is that the registering of pain or is it the reaction to the pain?

Dr. WAGER: It's both. It's very hard to actually separate those things out. But there - it's the perceptual part, the sensory part of pain coming in.

FLATOW: Right.

Dr. WAGER: Or actually, I should say input coming in that will become pain.

FLATOW: Right.

Dr. WAGER: Right. Pain itself is generated in your brain. Signals come in, so they're registered, they're attended to. They're - they elicit feelings, emotions about the pain, responses - I want to move away, but I shouldn't, I mean, the experiment, all those kinds of stuff.

So there's a whole set of regions that sort of comprise the sensory and the emotional and the evaluative - what's-happening-to-me, is-this-good-or-bad-for-me aspects of pain. And different regions, we think, are related to different things.

So with, you know, the placebo study, there's been a literature or people have done experiments and shown that giving somebody a placebo for pain has a sort of surprisingly powerful effect on what they report.

So if I give you the hot cup of coffee kind of stimulus, say it's a level, you know, I rate that as an eight out of ten...

FLATOW: Right.

Dr. WAGER: ...or something like that, right? I give you the same, the identical stimulus with a placebo and...

FLATOW: And you tell me it's placebo. You tell me it's a placebo?

Dr. WAGER: Yes. So what I tell you is this is a powerful analgesic drug. It's going to block pain. It's really going to help...

FLATOW: Right.

Dr. WAGER: ...you. So this is - and we - as I tell you, we put a cream on our skin and we say this is lidocaine. It's an effective - it's a known pain reliever. We want to see how it works in your brain. So then we give them the same stimulus, the same hot, you know, hot plate on their arm, instead of a level eight, maybe it's a level six.

FLATOW: Wow.

Dr. WAGER: So there's a drop.

FLATOW: So they believe that that placebo that you told them was something else is lessening their pain.

Dr. WAGER: Right. They believe it's lessening their pain. And based on what they tell us, then the pain goes down. Interestingly, this is used in the hospitals, also in the clinics. So it used to be that you give people morphine, you just give them whatever the dose that they're getting is.

But they found that if people know they're getting morphine and they can control the administration of morphine, it's a lot more effective. And some studies have shown that if you know you're getting the drug, it is perhaps, in some cases, nearly twice as effective as if you don't know you're getting it.

FLATOW: But we never knew why it worked before. You have uncovered some good clues of where and why it worked.

Dr. WAGER: So - and the reason we started this, the study - I'll tell you what we did - is because you might tell me something hurts less, but there might be many reasons that that might be true. You might just be telling me what I want to hear. You might just believe it hurts less, but your actual experience is the same.

So we went to the brain imaging in order to try to test whether there are changes in how your brain processes pain with the placebo. So we're scanning people's brains as we put - for each person, we put a cream on their arm, two creams actually, but they're exactly the same cream. One of them we say this is lidocaine. It's going to be terrific stuff. On a nearby patch of skin, we put the same cream, but we say this is not going to have any effect.

FLATOW: It's cold cream or something.

Dr. WAGER: Yeah. Not going to help you at all. And then, we alternate back and forth, giving the heat stimuli to each of those parts of the arm, and we're comparing the pain responses at each of those two sites. And then, because we're scanning the brain during those times, we can also see what the change in pain response in the brain is at the same time.

So what we found - and there's really a sort of series of studies over the last few years that have demonstrated this. We find that some of the pain responsive regions of the brain actually showed decreases in activity when you have the placebo.

So what that means for us is that there are changes in how your brain is actually processing the stimulus. There's something that's physiologically real about the placebo.

FLATOW: It's not just - well, it's all on your head actually. But you've actually found - the despondent showed - the brain is showing up that it thinks it's a placebo, and for the brain actually reacting to show you that it thinks it's a placebo by having less pain reaction.

Dr. WAGER: Right, exactly. So we can actually see changes in your brain and how you anticipate pain.

FLATOW: Right. It thinks it's the real thing, you know. Your anticipation is thinking that it's the real thing instead of a placebo.

Dr. WAGER: Right, your brain is thinking it's the real thing. And then, your brain is responding to the signals coming in, the painful signals, in a different way. Now, with our more - with this recent study that was just published, we sort of took this one step farther.

And one thing that people have trouble wrapping their heads around in some sense - or, I still do in a way, even - is that when you think something, when you expect something or believe something, it actually has an effect on your brain and it has - changes your neurochemistry.

So it is in your head. It's a thought. It's a concept - your belief about this is going to help me, this is going to be okay, this is going to be terrible. But there actually is an effect on your brain. And in this paper, we wanted to look at the neurochemistry of the placebo effect.

And in particular, we're looking at - now, for this study, we scan people's brains again, giving them pain. But we're looking at - we're using this technique, positron emission tomography, PET scanning.

FLATOW: Right.

Dr. WAGER: ...to look at people's brains. And here, in this case, we can actually see the activity in a neurochemical system, the opioid system. And opioids are a class of chemicals - endorphins are example - that are - they're highly addictive, they're feel-good chemicals. When you give people morphine or other related chemicals or drugs in the hospital that block pain, you're giving them opiates.

FLATOW: Mm-hmm. So do you actually - the brain put out opiates in response to the placebo.

Dr. WAGER: It does. It does.

FLATOW: It thinks it's a real thing.

Dr. WAGER: And that's - right. And that's the sort of major finding from the study...

FLATOW: Wow.

Dr. WAGER: ...is that we see - when you believe you're getting the pain relief, right.

FLATOW: Right. If - when you believe that this was real pain relief, it put out a painkiller.

Dr. WAGER: Exactly. Right. And...

FLATOW: Just from the placebo.

Dr. WAGER: Right.

FLATOW: Can you use this on - we've only about a minute or so left - can you use this in other - you say you do other mind-body connections, can you use this knowledge to treat other kinds of things besides a hot cup of coffee on your arm.

Dr. WAGER: Mm-hmm. So pain is just sort of one-model system that we can sort of control well. But, essentially, what this research can do is give us insight into how your thoughts and beliefs regulate your body in pain, in Parkinson's disease, depression, other anxiety disorders. There might be interactions with the immune system. And these are all things that we have to - that we need to investigate scientifically in order to document, you know, when placebo effects can work and in what ways they can work.

I think one of the sort of important and interesting take-home message is is that medical science has really, so far, ignored, to a large degree, people's beliefs and expectations, and pharmacology ignores it. But, in fact, because beliefs cause chemicals to be released in your brain, those chemicals actually can combine with drugs and do things that just the drugs themselves won't do.

FLATOW: Could you say I believe I'm going to get better and then release, you know, a positive thinking or religion, or any other kinds of those things possibly be involved here?

Dr. WAGER: Right, so this is - right. This is one of the potential mechanisms...

FLATOW: Yeah.

Dr. WAGER: ...whereby, things like positive expectations and beliefs - religious beliefs or faith - might have effects on your physiology, because those beliefs themselves are associated with release of chemicals in your brain that can do things like relieve pain, can increase your mood, may potentially interact with your immune system and so forth. But that's where we need a lot more research to really demonstrate those things...

FLATOW: Yeah, and you can start watching - for the brain-watching now, using these imaging techniques.

Dr. WAGER: Well, that's the really new thing. Before about 15 years ago, they couldn't do this kind of research at all.

FLATOW: Right.

Dr. WAGER: So this is a really totally new kind of - a way of looking at the living human brain that's really bringing psychology and neuroscience and medicine together in ways that haven't been possible before.

FLATOW: And your next step after this? Where would you take this research next?

Dr. WAGER: Well, we're looking now to see what kinds of effects in the body that these beliefs can translate into. We're looking beyond pain. We're looking at effects on emotions and how those emotions affect the body. And we're looking at other kinds - other ways of sort of looking at how this - your sense of control over the situation and other sorts of psychological things can...

FLATOW: Yeah. Yeah.

Dr. WAGER: ...affect your body, in pain and also in other sorts of emotion-related things.

FLATOW: We've run out of time.

Dr. WAGER: All right.

FLATOW: It goes by fast, doesn't it?

Dr. WAGER: It sure does.

FLATOW: I want to thank you for coming in and talking with us, Dr. Tor Wager, whose team has come up with some of these answers about placebo effect. He's assistant professor of psychology at Columbia University.

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