The Power of the Placebo Horizon


The Power of the Placebo

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This is a remarkable little pill.

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It comes in all shapes and sizes.

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It can relieve pain,

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treat depression,

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and has even helped ease the symptoms of Parkinson's Disease.

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And yet, it isn't a wonder drug.

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In fact, there isn't anything in it.

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As a scientist, it's unbelievable!

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These pills are placebos.

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Dummy pills. Sugar pills.

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I'm thinking, "He wants me to take sugar pills?

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"This isn't going to work."

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But the latest research is starting to show why placebos do work.

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And how you could make the most of them.

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At the home of British cycling, at the Manchester velodrome,

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some of the country's top cyclists have gathered together.

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They're elite.

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Many are national champions, past or present.

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They've been brought together by Dr Chris Beedie.

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He wants to see if he can give them some pills to help them

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do something that would normally take months of training.

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He wants to see if he can make them cycle faster than ever before.

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We're going to get all the riders onto the track

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to do a sprint time trial, to get an idea from that

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of their baseline speed,

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and then four hours later we're going to give them a couple of these.

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And we're expecting them to have an effect on their performance.

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The cyclists have been invited to take part in an experiment

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looking at the effect of legal performance-enhancing supplements.

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We're looking at testing a new ergogenic aid.

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Half of you will be getting what we'd call a standard ergogenic aid,

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which is caffeine.

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The other half will be getting caffeine,

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with some nitrate and some bicarbonate in those capsules.

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And we're expecting that to do slightly better.

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So to evaluate this we need two time trials from you,

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absolutely 100%,

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absolutely everything you've got in both time trials.

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The cyclists' baseline performance is measured

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to get a sense of their natural competitive time.

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And then - it's time for the pills.

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OK, we've got the baseline performance,

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we now are going to give them some of these and see what effect these have.

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One by one, the cyclists receive their performance-enhancing capsules

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from members of Chris' team.

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Hi, Lisa, you've been randomised today to receive the caffeine.

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Today you've been randomised to take the mixed supplement.

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Hannah, today you've been randomised to receive the pure caffeine.

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Today you've been randomised to receive the new supplement.

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But nothing about today is quite as it seems.

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Both sets of pills are exactly the same.

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The cyclists are actually taking part in a very different experiment.

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These are the capsules we're going to be using today.

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We've got a couple of red ones and a couple of red and white ones.

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They're fairly large and they look like they mean business.

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They are, however, filled with cornflour.

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Chris wants to see if the cornflour can improve the cyclists' times,

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even though they already do all they can to be as fast as possible.

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But, having raced just a couple of hours ago, the riders are tired.

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The thought of doing two in one day, it would never happen.

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You'd normally sort of race one,

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and then a day or so, you'd start again... Two in one day's going to be interesting!

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It's fair to expect that their second race of the day would be slower.

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It's time to see what the pills can do.

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Do you feel that the second ride felt easier?

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The first one, it got progressively harder during the ride.

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The second ride, after about a lap and a half out of the four laps,

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it kind of got to a point where it was hurting but then it never got any worse.

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The second ride felt better, yes.

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I went half a second quicker, which is quite a lot over that distance.

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I felt as if I was a little bit quicker second time round.

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I felt really tired before I took it.

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I think it may have started to kick in whilst I was warming up

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and I got a bit of a burst of energy and I felt ready to go again.

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In spite of the fact that the riders were tired from their earlier race,

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analysis of today's times shows that more than half of them

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were quicker with the cornflour.

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The placebo has even helped one cyclist

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to ride faster than ever before.

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It was really good,

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really surprised to go quicker in the second run.

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And a personal best as well by two tenths of a second,

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and to beat a couple of the lads that are here today that normally beat me,

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big surprise, yeah, really happy.

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-So, you did a PB, you felt the effects of the substance.

-Yeah.

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Um, the capsule we gave you was a placebo.

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Oh, right, OK.

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-Really?

-SHE LAUGHS

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Really? Wow.

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Today's trial is just a demonstration of what placebos can do.

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But it's typical of what Dr Beedie has found

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in over a decade of experiments with hundreds of athletes.

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Every study we've done we found a mean placebo effect.

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In sports performance generally,

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we can see improvements quite frequently of two to three per cent.

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Well, three per cent in many sports is probably the difference between

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first place in the Olympics and not being in the top ten.

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So we're talking quite a substantial difference.

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It's a little bit like your car's going a little bit faster

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but you're not using any more petrol.

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Why that's happening, however, is still open to question.

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It seems the pills that the cyclists took

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have the potential to make a real difference -

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and it's clearly nothing to do with the cornflour in them.

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So how can a pill with nothing in it

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help someone to cycle faster than ever before?

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Since the advent of modern medicine,

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placebos have been treated with scepticism.

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It's been assumed that they can do nothing.

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They've been used only as dummy pills

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that new drugs have to beat to be considered effective.

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But in recent years a number of studies have shown

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that there may be more to a placebo than we thought.

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A few years ago,

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Dr David Kallmes decided to do a rather controversial experiment.

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For 15 years, he's been fixing broken backs by injecting them

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with a special kind of surgical cement.

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We saw terrific results from the procedure,

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really amazing results from the procedure.

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But then Dr Kallmes noticed something

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that made him question how effective the procedure was.

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I was aware of some rare cases where, believe it or not,

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the wrong vertebral body was treated, for whatever reason,

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and patients seemed to get some relief from that.

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So there was some reason to suspect that there were numerous factors

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at play in the apparent effectiveness of the cement.

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He decided to do something unusual.

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He decided to put this established procedure to the test.

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He designed a trial in which some patients would be given

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the real procedure...

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and some would be given a placebo.

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But in this case, the placebo couldn't be a dummy pill -

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it would have to be a fake operation.

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There was scepticism from many people

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about whether this was worth doing.

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I recall being at a meeting and I remember being screamed at

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and then later on being called a heretic for raising the spectre

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of the placebo effect in interventional procedures.

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Nevertheless he went ahead with the trial.

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All he needed was to recruit some patients.

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A few years ago, Bonnie Anderson had an accident

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that led her to join the trial.

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Well, when I slipped on the tiled floor in the kitchen here,

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I went complete... feet went out from underneath me,

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I went flat on my back. I could not move.

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And I thought, oh, dear, I told Don, I said,

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"I'm afraid I broke my back." The pain was just very, very severe.

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I couldn't stand up straight, I'd have to hold onto something.

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She was in pain all the time, she could do very little.

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I'd help him with the dishes,

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but he did all the vacuuming, he did more of the workload.

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-That part hasn't really changed that much!

-Oh, shut up!

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When Bonnie saw the doctor, a vertebral fracture was confirmed.

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She was enrolled on the trial.

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On a cold October morning, Bonnie arrived at the hospital,

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ready for her operation.

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She couldn't know whether she was having a vertebroplasty

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or the pretend procedure - the placebo.

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Dr Kallmes developed an elaborate ruse

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to ensure that patients wouldn't work out which group they were in.

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The patient was brought into the room, was given medication by vein,

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was sterilely prepped and local anaesthesia was given.

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And only after the anaesthesia was given onto the bone

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did we press the button to see whether the patient was randomised

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to the full vertebroplasty or to the placebo.

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In both cases, no matter how they were randomised,

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we then opened the cement, which has a very strong odour like nail polish remover,

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to really simulate it for everybody in the room.

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And if they were randomised to vertebroplasty,

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we then injected cement down into the bone.

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If they were randomised to placebo...

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..we opened the cement,

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we had a script that we followed...

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..we pressed on the back and said,

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"OK, ma'am, the cement is going in now, everything's going fine,

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"things are going well, few more minutes here. OK, we're all done."

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So we really simulated the procedure for the patient.

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Bonnie felt better immediately.

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The surgery did work very, very well for me.

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It did so much for me. I was really active.

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The procedure transformed her life.

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Within a week of the injection, I was able to play golf.

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I took it a little easy, but I was able to play golf almost every day.

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And I returned to some of my duties, as far as...

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Well, I don't vacuum, but as far as dishes and stuff.

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He won't say that, but it's true.

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But Bonnie didn't have the real procedure.

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She was in the placebo group.

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And what made her so interesting

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was that she'd already had a real vertebroplasty once before.

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Which meant she was uniquely able

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to compare the real thing with the placebo.

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I thought they were both so successful

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that I could go ahead and do what I wanted to do without any problem.

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And it wasn't just Bonnie that responded so well to the placebo.

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When the results of the other 130 patients on the trial came in,

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they surprised everyone.

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There was no statistically significant difference

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in degree of pain relief

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between the patients who underwent vertebroplasty and placebo,

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and more importantly there was no statistically significant difference

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in improvement in function

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between the patients who underwent vertebroplasty and placebo.

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This study and another in Australia both suggest

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that a pretend procedure can be as effective as vertebroplasty -

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which has been carried out on over a million people.

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Both the real thing and the placebo made patients better

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than if they'd received no treatment.

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So how could a pretend procedure be so effective?

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Around the world, scientists are investigating how a placebo works.

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They're trying to find out what's happening inside your body and brain

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when you experience a placebo effect.

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It's a public holiday in the Italian Alps.

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Tourists are heading up the mountain

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to spend a day skiing in the shadow of the Matterhorn.

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But, for Fabrizio Benedetti, it's just another day in the office.

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Instead of driving to the lab,

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instead of taking a bus or a train, we take a cable car.

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# On days like these

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# When skies are blue... #

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The landscape is beautiful, it's a beautiful day.

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But Fabrizio's laboratory isn't at the top of the mountain

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just for the sake of a pleasant commute.

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He's using the low oxygen levels at high altitude

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to conduct an unusual experiment.

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He's trying to find out whether a placebo effect is imagined,

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or whether somehow a placebo can cause real changes in our bodies.

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OK, so here we are inside the station.

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There are a couple of labs.

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We have a living area, we have two bedrooms, the kitchen, the bathroom.

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Italian-Swiss border is more or less here.

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We work in Switzerland, we sleep in Italy.

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For the past few years, Fabrizio has been bringing volunteers,

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like Marco, to his mountain-top laboratory to be studied.

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He's conducting an experiment to see if anything happens to people

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when they expect extra oxygen, but don't actually get it.

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So what we do is we give real oxygen or placebo oxygen -

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the tank of the oxygen is empty -

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and we compare the effect of real oxygen with placebo oxygen.

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Fabrizio gives Marco a canister of what he's told is oxygen,

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and sets him off on a 30-minute hike.

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Even mild exercise, that's pretty tiring and difficult.

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That's the reason why we are here, of course.

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Fabrizio wants to know as much as possible

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about what's going on inside Marco's body and brain.

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His heart rate, brain activity,

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and even the neurotransmitters in his system, are all being monitored.

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At this altitude, extra oxygen would be a great help.

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If there is extra oxygen, of course, the muscles get more oxygen

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so their performance improves.

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As they hike further,

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Marco is easily able to outpace Fabrizio's team of scientists.

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You can see I cannot see him any more, actually.

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But, of course, Marco doesn't have any extra oxygen.

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So, has the fake oxygen just given him

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some kind of psychological boost?

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Or has it changed something in his body?

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By analysing the data he's gathered

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from Marco and the other subjects he's studied,

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Fabrizio has the answer.

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It's all to do with the level of a neurotransmitter called PGE2.

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When we come to high altitude,

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the low oxygen levels cause our blood oxygen levels to fall.

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This makes our PGE2 levels go up.

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And that leads us to feel some of the familiar symptoms

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of altitude sickness, like pain.

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But extra oxygen can ease the problems.

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When we give oxygen, there is a dramatic decrease in PGE2.

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This is the typical response

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after oxygen administration with real oxygen.

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The lower PGE2 level that comes from giving oxygen

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helps us to feel less pain, and therefore work harder.

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But if you give someone fake oxygen

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you wouldn't expect the PGE2 levels to change.

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In this case we give fake oxygen, which means placebo oxygen,

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and there's no change in blood oxygen saturation, you see -

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we have 84% of blood oxygen saturation -

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but there's a decrease in PGE2 anyway.

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This means that this decrease is not due to oxygen in the body,

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but is due to expectation, to a placebo effect.

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The fake oxygen is causing real physiological changes

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in Fabrizio's subjects -

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decreasing their levels of PGE2,

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causing them to feel less pain, and allowing them to work harder.

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It's not imagination, it's not pure psychological effect,

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it's a real neurobiological effect.

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Somehow, fake oxygen is producing

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real chemical changes in people's bodies.

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It shows us just how real and measurable

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the placebo effect can be.

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What it doesn't tell us is how that's happening.

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Boulder, Colorado...in the foothills of the Rocky Mountains.

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Tor Wager is trying to figure out

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how a placebo can change the chemicals in our bodies.

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He's getting ready for another day inflicting mild torture on someone.

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We do the thermal pain test a lot because it's not damaging

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and it's safe, but it is painful.

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Right, Jake, come on in, you can have a seat right here.

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Tor is hoping to fool Jake into believing

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that a standard moisturiser is a powerful pain relief cream.

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He begins by applying some moisturiser to Jake's arm,

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and tells him what it is.

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This is just to have something on your skin.

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It won't provide any pain relief, and will serve as a control.

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OK.

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On a different spot, he applies some lidocaine -

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a local anaesthetic - which will dampen the pain that Jake feels.

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We already know that it blocks pain, but we're just going to look

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-and see whether it changes pain in your brain.

-OK.

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And finally, there's more moisturiser.

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But Jake is told that it's also a local anaesthetic.

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We'll do the analgesic on both of these spots.

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We'll just wait just a minute for that to take effect.

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Jake will then be subjected to heat pain on the different sites

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and be asked to rate them.

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Meanwhile his brain will be scanned,

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allowing Tor to learn more about how a placebo works.

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So we're going to give you a series of your level 8 temperatures, Jake.

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And just use the trackball there, and just rate what you feel,

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moment by moment, track your pain continuously.

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OK, so we're ready to go in.

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This is the pain rating scale, he's rating his pain continuously,

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and the anchors here are no sensation to strongest imaginable sensation.

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Jake's first heat treatment is on the control area.

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All right, Jake, we've got it tuned

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and ready to go for the first task here, OK?

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With no anaesthetic, it's not a pleasant experience.

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It's going up

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and it's just above very strong.

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Oh, that's big, that's good!

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That was the control, this is with the lidocaine,

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just rate what you feel, we'll be scanning.

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On the lidocaine site, the pain is noticeably reduced.

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So with the control cream, they were between very strong

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and strongest imaginable, so they were pretty high.

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And with the actual lidocaine cream

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they were between strong and very strong,

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so there was a substantial drop.

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But how will Jake fare when the same heat is applied

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on the moisturiser that Tor has said is lidocaine?

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Last one, lidocaine number 2.

0:25:460:25:48

When he felt this temperature on the control area,

0:25:510:25:54

he rated his pain above very strong.

0:25:540:25:58

Let's see what happens.

0:25:580:25:59

Oh, this one is the lowest so far actually,

0:26:110:26:13

so that trial is lower than any of his lidocaine trials actually.

0:26:130:26:17

The basic conclusion is that here the placebo response for him

0:26:180:26:22

is about as large as the lidocaine responses.

0:26:220:26:25

OK, Jake... so how did that feel, by the way?

0:26:260:26:29

-Feels less painful.

-Feels less painful?

-Yeah.

0:26:290:26:32

So I told you before that we were applying the real lidocaine on all four sites, right?

0:26:340:26:39

But actually we didn't apply the lidocaine on all the sites.

0:26:390:26:42

So what we actually did is we applied the control here,

0:26:430:26:46

so this is where your pain ratings were highest.

0:26:460:26:49

These two were both the real lidocaine,

0:26:490:26:52

-and these two were the placebo.

-Interesting.

0:26:520:26:54

So, knowing that, do you feel like it worked?

0:26:540:26:57

Or do you feel like, um...

0:26:570:26:59

-The lidocaine or the placebo?

-The placebo.

-Definitely, yes!

0:26:590:27:02

The significance of Tor's work

0:27:050:27:07

is that by scanning the brains of people as they experience

0:27:070:27:10

a placebo effect, he's revealed clues about how a placebo works.

0:27:100:27:17

So when we've given people a placebo treatment, what we see is the release

0:27:170:27:22

of endogenous opioids, which is the brain's own morphine,

0:27:220:27:26

in a number of brain areas

0:27:260:27:28

including this area here which is the periaqueductal grey,

0:27:280:27:31

which is really a critical site for opioid-mediated pain control.

0:27:310:27:35

What that means is that the placebo effect

0:27:400:27:43

is tapping into some of the same pain control circuitry

0:27:430:27:47

as opiate drugs, like morphine.

0:27:470:27:49

What Tor has shown

0:27:520:27:54

goes to the heart of the mechanism of how a placebo works.

0:27:540:27:58

A dummy pill or cream or surgery can release

0:27:580:28:02

the naturally-occurring painkillers in our brains.

0:28:020:28:06

And it isn't just painkillers that a placebo can activate.

0:28:070:28:11

Our brains are capable of producing countless chemicals that we need -

0:28:160:28:21

to stop pain or to feel it,

0:28:210:28:23

to energise us or to help us sleep.

0:28:230:28:27

And a placebo can mimic many of them - from aspirin to alcohol.

0:28:290:28:34

The placebo effect taps into our natural pharmacy.

0:28:360:28:39

Drugs work because we have receptors for the drugs,

0:28:400:28:43

and that means that there's some endogenous chemicals

0:28:430:28:46

that our brains are producing that act on those receptors -

0:28:460:28:49

the receptors evolved to respond to those natural chemicals.

0:28:490:28:54

So, a placebo can produce real results

0:28:550:28:58

by tapping into the chemical systems that our bodies have evolved.

0:28:580:29:02

Just like modern medicines, a placebo effect relies on chemicals -

0:29:040:29:09

the chemicals in our brains.

0:29:090:29:11

Scientists want to know just how much a simple sugar pill can do.

0:29:200:29:24

Can it only affect conditions which rely on self-reporting -

0:29:260:29:29

like pain - or could it do much more?

0:29:290:29:34

Paul Pattison lives on the outskirts of Vancouver.

0:29:490:29:53

It gives him easy access to the woods and mountains

0:29:530:29:55

on the edge of the city.

0:29:550:29:57

But 12 years ago life took a turn for the worse,

0:29:570:30:02

when he started to develop some unsettling symptoms.

0:30:020:30:05

I started to notice I was not... my stride wasn't right,

0:30:060:30:09

and I-I-I...my doctor referred me to a podiatrist,

0:30:090:30:13

thinking something was wrong with my ankle, my foot, whatever.

0:30:130:30:16

So the podiatrist had me in there a couple of weeks later and he goes,

0:30:190:30:23

"Oh, my gosh, you don't need a podiatrist, you need a neurologist."

0:30:230:30:26

So I went back to my GP, got referred to a neurologist

0:30:270:30:30

and he took one look at me and said, "OK, you have Parkinson's."

0:30:300:30:35

Well, holy smoke! That was...

0:30:370:30:39

that was quite traumatic, I was in tears for sure.

0:30:390:30:42

It came as a complete shock to Paul and his family,

0:30:450:30:48

and eventually forced him to give up his job.

0:30:480:30:51

Parkinson's is caused by an inability of the brain to release dopamine.

0:30:540:30:59

As well as affecting our mood,

0:31:000:31:02

dopamine helps to regulate our movement.

0:31:020:31:05

With medication, Paul can get the dopamine he needs

0:31:060:31:09

to keep his symptoms under control.

0:31:090:31:12

So I take Sinemet CR, control release, is the pink one.

0:31:130:31:17

And the two white ones are 2.5mg each of Bromocriptine

0:31:170:31:22

and as you see, I'm upright, I'm mobile, my shoulders are back.

0:31:220:31:26

A few years ago, Parkinson's researcher Professor Jon Stoessl

0:31:310:31:35

decided to test this effective medication against a placebo.

0:31:350:31:39

We've always known

0:31:400:31:42

that how people do when they have a serious condition

0:31:420:31:47

has a lot to do with their attitude

0:31:470:31:50

and that's intriguing to me.

0:31:500:31:52

Paul was recruited onto Jon's trial.

0:31:530:31:56

It would require him to stop taking his medication.

0:31:560:32:01

Without it, even walking can be difficult.

0:32:010:32:04

About a year and a half ago, I guess, I was about 50 feet from my house,

0:32:050:32:11

I could literally see the front door.

0:32:110:32:13

I was sitting on the sidewalk, on the kerb, and I couldn't get home.

0:32:130:32:17

That was...that was something else.

0:32:180:32:21

Took me about a half-hour to get home...from a hundred feet.

0:32:220:32:26

Yeah.

0:32:260:32:27

Paul headed into hospital for the trial,

0:32:340:32:37

without having had his medication,

0:32:370:32:39

his Parkinson's symptoms in full flare-up.

0:32:390:32:42

And that's when they gave me this capsule.

0:32:430:32:46

And they gave you a half-hour, 45 minutes, you know,

0:32:480:32:50

a normal period of time for the meds to kick in.

0:32:500:32:53

And boom, I was thinking, ah, this is pretty good.

0:32:570:33:00

My body becomes erect, my shoulders go back

0:33:000:33:04

and I needed to go to the bathroom

0:33:040:33:07

so I said, "I don't need any help, I'm fine."

0:33:070:33:10

And I heel-struck my way down the hall and went to the bathroom.

0:33:100:33:15

But Paul hadn't been given any active medication.

0:33:160:33:20

He'd been given a placebo.

0:33:200:33:21

Well, I was shocked.

0:33:260:33:27

There's no way I could have done that.

0:33:270:33:29

I fully understand the effects of my medicine.

0:33:290:33:33

So how could a nothing create those same feelings?

0:33:330:33:37

Yeah, I was really shocked.

0:33:380:33:40

Brain scans of patients with Parkinson's that were responding to the placebo

0:33:440:33:49

helped to explain how Paul's symptoms had faded.

0:33:490:33:53

This slide shows three scans all taken from the same person

0:33:530:33:59

with Parkinson's disease.

0:33:590:34:01

So, now you see the activity at baseline.

0:34:010:34:04

When they come in with no medication,

0:34:040:34:07

their Parkinson's is not well controlled,

0:34:070:34:10

there's a loss of dopamine in the brain,

0:34:100:34:12

so we see lots of activity here.

0:34:120:34:14

With so little dopamine,

0:34:160:34:17

someone with Parkinson's would be struggling to move and function.

0:34:170:34:21

Now we look at the middle slide

0:34:220:34:25

and this is after the person is told that they're going to get

0:34:250:34:30

active drug, but in fact they receive placebo.

0:34:300:34:34

And you can see a striking reduction in activity here

0:34:340:34:38

which indicates that their brains have released a lot of dopamine.

0:34:380:34:42

The intense red colours in the striatum area of the brain

0:34:440:34:48

show how little dopamine is present at baseline.

0:34:480:34:51

The decrease in the red colouring

0:34:530:34:55

shows how the placebo can release dopamine just like the real drugs.

0:34:550:35:00

What we found is that, in somebody with Parkinson's disease,

0:35:040:35:08

a placebo can release as much dopamine as amphetamine or speed can

0:35:080:35:13

in somebody with a healthy dopamine system.

0:35:130:35:16

So it's a very dramatic response.

0:35:160:35:18

There are physical things that change in me when I take my meds

0:35:200:35:24

and I didn't think a placebo would be capable of, you know...

0:35:240:35:28

There's no way - you know, how could a sugar pill or whatever,

0:35:280:35:31

you know, make me feel like I had taken my Sinemet?

0:35:310:35:34

I'm thrilled to death to know that I still have the ability

0:35:340:35:36

on a short-term basis to produce dopamine and get going, right?

0:35:360:35:39

Several studies have now shown that a placebo can ease

0:35:410:35:45

the symptoms of Parkinson's - even if only in the short term.

0:35:450:35:49

Once again, the placebo works

0:35:500:35:53

by tapping into the brain's internal pharmacy.

0:35:530:35:55

All these studies raise another intriguing question.

0:35:570:36:00

For a placebo to work, why do we need to believe that it's real?

0:36:040:36:09

Pull your body into the rock, that's nice.

0:36:200:36:22

For Tor Wager, it's all about our expectations.

0:36:240:36:27

They can make a difference to what happens in our bodies -

0:36:310:36:34

and that's true whether you take a pill,

0:36:340:36:37

undergo an operation or climb a mountain.

0:36:370:36:42

Stand up on that back foot, Tor.

0:36:420:36:44

Climbing is a dangerous sport.

0:36:470:36:50

One false move, and things could go badly wrong for Tor -

0:36:500:36:55

except, of course, that he's got a rope.

0:36:550:36:58

And that changes everything.

0:37:000:37:02

-Going right. Watch me here.

-Good.

0:37:020:37:06

He expects to be safe.

0:37:060:37:08

Step through, beautiful, that's it.

0:37:080:37:10

And yet, without his belief that everything will be OK,

0:37:120:37:15

he'd be so nervous he could barely climb.

0:37:150:37:17

When I was up there on the rock, my heart started beating,

0:37:200:37:23

blood flow changed to my fingers, my brain's releasing opioids,

0:37:230:37:27

releasing dopamine, and all those things are helping me perform,

0:37:270:37:30

and they're also having various impacts on my body.

0:37:300:37:33

Those impacts depend on the feeling, the knowledge that I'm safe.

0:37:340:37:38

Take off that rope, it would be a completely different world -

0:37:380:37:41

my heart rate would go crazy, I'd be sweating, and so forth.

0:37:410:37:46

Ultimately, it's about the link between our minds and our bodies.

0:37:480:37:53

Whether it's fear or hope, our thoughts and expectations

0:37:550:38:00

can trigger chemical reactions that change our bodies.

0:38:000:38:04

So, if we expect a placebo to do something,

0:38:060:38:10

it can release chemicals in our brains and change our physiology.

0:38:100:38:15

Scientists are now exploring

0:38:190:38:21

just how much our expectations are capable of.

0:38:210:38:24

As well as pain, they've found that placebos can alleviate conditions

0:38:250:38:30

from depression to insomnia,

0:38:300:38:33

nausea to attention-deficit disorder.

0:38:330:38:36

And because it's all about your expectations, even the size

0:38:380:38:43

and shape of a pill can make a difference to how well it works.

0:38:430:38:47

Studies have shown that capsules are more effective than tablets.

0:38:480:38:53

A large capsule is better than a small capsule.

0:38:540:38:57

Expensive medications are more effective than cheap medications.

0:38:570:39:02

Colour makes a difference -

0:39:020:39:04

red pills are more effective for treating pain,

0:39:040:39:08

blue pills are more effective for treating anxiety.

0:39:080:39:12

Unless you happen to be male and Italian,

0:39:140:39:16

in which case blue is the colour of your national football team,

0:39:160:39:20

and a symbol of immense excitement, passion, and heartache.

0:39:200:39:25

In that case, according to research,

0:39:250:39:28

a blue pill won't help relax you - it will do the opposite.

0:39:280:39:32

But there are clear limits to what placebos can do.

0:39:340:39:37

They certainly won't fix a broken leg or help to shrink a tumour.

0:39:380:39:43

But in the areas where they seem effective,

0:39:440:39:46

scientists are beginning to wonder how we can make the most of them.

0:39:460:39:51

There is, however, a problem with dummy pills and sham surgeries.

0:40:010:40:05

They rely on deception.

0:40:050:40:07

You're not told the truth.

0:40:080:40:11

That seems to be why they work - because you think they're real.

0:40:110:40:15

Obviously doctors don't want to lie to their patients.

0:40:160:40:20

So how do we harness the power of the placebo effect without lying?

0:40:200:40:25

It's a question that one of the most prestigious medical schools in the world is hoping to answer.

0:40:290:40:35

In 2010, Harvard established a Program in Placebo Studies.

0:40:370:40:42

It aims to work out how we can use the placebo effect

0:40:420:40:47

to make people better.

0:40:470:40:49

Ted Kaptchuk is the Director.

0:40:490:40:52

In the last 15-20 years,

0:40:520:40:53

there's been an explosion of research in placebo studies.

0:40:530:40:56

We've learnt so much, but there's so much more to do.

0:40:560:40:59

The underlying goal is how do we learn to harness it and use it

0:41:010:41:05

to help people get better, healthier and stronger lives?

0:41:050:41:08

Recently, Ted decided to challenge

0:41:100:41:13

one of the most basic assumptions about placebos.

0:41:130:41:16

He decided to conduct an experiment to see

0:41:160:41:19

whether we really need to be duped for a placebo to work.

0:41:190:41:24

The conventional wisdom was that you have to use either deception

0:41:240:41:27

or concealment in order for a placebo to work.

0:41:270:41:30

We decided to test whether or not you could still get a placebo effect

0:41:300:41:35

if you gave a person a placebo and told them it was a placebo.

0:41:350:41:38

Linda Buonanno has suffered from irritable bowel syndrome for 16 years.

0:41:400:41:45

At times, the symptoms are bad enough

0:41:450:41:48

that she doesn't want to leave home.

0:41:480:41:50

Along with 80 other sufferers of IBS,

0:41:500:41:53

she was recruited onto Ted's trial.

0:41:530:41:56

She was given some pills and told they were a placebo,

0:41:560:42:00

with no active ingredient,

0:42:000:42:03

but that they might work, thanks to her own self-healing processes.

0:42:030:42:08

I said, "What? A placebo?"

0:42:080:42:10

Because I'd just finished college as a medical assistant

0:42:100:42:13

and I'm thinking, "He wants me to take sugar pills?

0:42:130:42:16

"This isn't going to work."

0:42:160:42:18

But I said I'd do it, so I went home, I started taking 'em...

0:42:180:42:22

..and after three days I realised I wasn't in any pain any more.

0:42:330:42:37

I didn't have any intestinal pain,

0:42:390:42:41

I didn't keep running to the bathroom or anything like that.

0:42:410:42:45

I didn't have any stomach cramps, I had nothing, all the symptoms,

0:42:450:42:49

the severe symptoms I had, were gone.

0:42:490:42:51

I thought, no, this is not happening,

0:42:540:42:56

this can't be, a sugar pill does not get rid of the problems, right?

0:42:560:43:00

Linda wasn't the only study participant who reported

0:43:020:43:05

improved symptoms from a pill she knew to be inactive.

0:43:050:43:09

I was taken aback when we finished the trial

0:43:100:43:12

and our statisticians showed us the results

0:43:120:43:15

and it was much stronger than we expected.

0:43:150:43:17

62 per cent said they got adequate relief

0:43:170:43:20

from being on the placebo pill.

0:43:200:43:22

People who got nothing, I think it was around 30%, said they had adequate relief,

0:43:220:43:26

so there's a real big difference, it was easy to detect.

0:43:260:43:29

But the study - and the supply of placebo pills -

0:43:300:43:33

only lasted a few weeks.

0:43:330:43:35

When the pills ran out, Linda's problems returned.

0:43:360:43:40

It was three weeks, I think it was, and everything was fine,

0:43:410:43:44

and then all of a sudden I'm not taking 'em any more

0:43:440:43:47

and all the symptoms came back.

0:43:470:43:49

It was horrible, it was like,

0:43:490:43:51

oh, man, I've got to suffer with this again?

0:43:510:43:53

Linda decided to try and buy some more placebo pills.

0:43:580:44:02

I tried to go to one of the health food stores

0:44:050:44:07

to buy the placebo pills but they didn't have them.

0:44:070:44:10

The fella in the store was, you know,

0:44:140:44:16

thought it was kind of odd why I would be asking for placebo pills.

0:44:160:44:19

They had nothing else that would replace it,

0:44:190:44:21

so I couldn't do anything, I was really disappointed.

0:44:210:44:24

Well, several patients actually asked us for more placebo pills.

0:44:240:44:29

Our Ethics Committee only gave us permission for three weeks

0:44:290:44:32

of treating people with placebo pills, and, as you can imagine,

0:44:320:44:35

I don't believe they're listed as a labelled drug in the United States.

0:44:350:44:41

So we weren't able to prescribe after that.

0:44:410:44:43

It's hard to know why Linda's symptoms disappeared,

0:44:430:44:47

when she took something that she knew was chemically worthless.

0:44:470:44:52

The study only looked at whether it would work, not why.

0:44:530:44:57

But Ted has a theory.

0:44:570:44:59

What I think happened is that just seeing our study physician...

0:45:000:45:06

..taking pills two times a day, in some way your body feels,

0:45:080:45:13

recognises, moves in a way that's moving towards health.

0:45:130:45:16

This is the body knowing something that's beyond their ability

0:45:160:45:20

to consciously be aware of.

0:45:200:45:23

I don't understand it, I don't know why and probably never will.

0:45:230:45:26

But there's something. I think I'm wishing for a cure

0:45:260:45:30

and I'm wishing for something to make this all disappear.

0:45:300:45:33

I think if I wish hard enough, it'll work, I guess.

0:45:330:45:36

Exactly why the pills worked remains a mystery.

0:45:390:45:42

And a small, short-term study like this certainly doesn't mean

0:45:420:45:47

that we can simply replace real drugs with placebos.

0:45:470:45:51

But it does call into question

0:45:510:45:53

the fundamental assumption about placebos -

0:45:530:45:56

the idea that we need to be duped for them to work.

0:45:560:46:00

At Harvard, other scientists are searching for ways

0:46:020:46:05

that we can use the power of the placebo without deception.

0:46:050:46:09

One of Ted's colleagues has studied something you might have thought

0:46:090:46:14

wouldn't have anything to do with placebos.

0:46:140:46:17

And that is hypnosis.

0:46:170:46:19

There's a lot of overlap between the idea of placebo

0:46:200:46:24

and the idea of hypnosis.

0:46:240:46:26

Separate the two index fingers.

0:46:270:46:29

And lift your hands and your arms up.

0:46:290:46:32

First of all, they're all based on belief, expectation and suggestion.

0:46:320:46:38

A hypnotic induction is a procedure

0:46:400:46:42

that has no active ingredient except for the person's belief

0:46:420:46:46

and understanding about what it is supposed to do.

0:46:460:46:49

Mike Gow is a dentist and a hypnotist.

0:46:520:46:55

He's preparing David for a major procedure.

0:46:560:46:59

He's going to extract his wisdom tooth.

0:46:590:47:02

So, as you can see from his X-ray, a lower wisdom tooth never developed

0:47:040:47:08

in the first place and that's why the upper tooth is actually

0:47:080:47:11

erupting down into the space where that tooth would've been.

0:47:110:47:14

When that happens, the tooth starts rubbing into the cheek,

0:47:140:47:17

it starts biting down on the gum below,

0:47:170:47:19

it also becomes very difficult for David to clean,

0:47:190:47:22

and actually he's got some decay in this tooth,

0:47:220:47:25

so almost impossible to get in to do a standard filling or restoration,

0:47:250:47:29

and the tooth is in danger of breaking down and decaying further.

0:47:290:47:33

Normally, removing a wisdom tooth would require

0:47:330:47:36

the injection of a strong local anaesthetic.

0:47:360:47:39

But David doesn't want one.

0:47:390:47:42

I don't like getting the injections

0:47:420:47:44

and having the numb mouth afterwards.

0:47:440:47:46

So I had the opportunity to have hypnosis as a treatment

0:47:460:47:51

for getting the wisdom tooth removed and I thought I'd give it a go.

0:47:510:47:55

David is having no pharmacological anaesthetic today.

0:47:580:48:02

He's not taking anything, he's not having any injections,

0:48:020:48:05

this is going to be just hypnosis. This is the plan, of course.

0:48:050:48:09

If we need to use anaesthetic, then we have it.

0:48:090:48:12

The only active ingredient in David's pain relief will be

0:48:120:48:16

the way Mike interacts with him -

0:48:160:48:19

his hypnotic induction.

0:48:190:48:21

Just notice this wave of relaxation now,

0:48:230:48:27

more and more in control of your thoughts and feelings,

0:48:270:48:33

calmer and calmer.

0:48:330:48:35

And if I lift the left hand all the way up...

0:48:370:48:39

The act of inducing hypnosis is a way of giving the person

0:48:410:48:47

permission, disinhibiting them,

0:48:470:48:50

so that they can now believe in their own abilities to block pain,

0:48:500:48:55

to experience things differently.

0:48:550:48:57

Just notice how the index finger and thumb just feel kind of dull

0:48:580:49:03

and insensitive, don't they?

0:49:030:49:05

Yeah?

0:49:060:49:07

Are you happy now to transfer that feeling around the tooth?

0:49:080:49:12

Cold...

0:49:140:49:16

dull, and insensitive.

0:49:160:49:18

David's wisdom tooth is firmly encased

0:49:260:49:29

in the bone that surrounds it.

0:49:290:49:31

Mike's first job is to gradually enlarge the socket.

0:49:310:49:35

DISTORTED: And just notice now, as you allow the mouth to open,

0:49:380:49:42

just feeling that pressure.

0:49:420:49:45

Relaxed...

0:49:450:49:48

..and comfortable.

0:49:500:49:51

Throughout the procedure,

0:49:510:49:53

David has been told to rate his pain on a zero to ten scale.

0:49:530:49:58

And just write down a wee number now.

0:49:580:50:00

A zero, that's excellent.

0:50:010:50:03

As you allow the mouth to open again,

0:50:070:50:10

just pushing and pressure,

0:50:100:50:14

comfortable...sensations.

0:50:140:50:18

Again, just write down any little number.

0:50:190:50:23

A one.

0:50:230:50:25

Clearly, David's pain scores aren't low

0:50:270:50:29

because of any painkilling drugs he's received.

0:50:290:50:32

It's his own internal painkilling systems that are working -

0:50:320:50:37

the same as those that can be activated by a placebo.

0:50:370:50:41

You might think of hypnosis as a procedure that allows people

0:50:410:50:46

to turn on their own ability to produce a placebo effect.

0:50:460:50:52

Having widened the socket sufficiently,

0:50:530:50:56

Mike is ready for the critical moment -

0:50:560:50:58

tearing the tooth from the ligament that holds it in place.

0:50:580:51:02

Calm...

0:51:020:51:04

control.

0:51:040:51:06

Eyes open. Wide awake.

0:51:180:51:20

That was awesome. Very well done.

0:51:200:51:22

Good. So, the final moment of removing the tooth,

0:51:240:51:27

there's a lot of pressure,

0:51:270:51:29

and I'd be interested to know what number you were at.

0:51:290:51:33

It was...probably a four-ish.

0:51:330:51:36

-About a four.

-In the final moment, yeah.

0:51:360:51:39

Without any form of pain relief, I would expect it to be an 8 or a 9,

0:51:390:51:43

without anything at all, so I think a number 4 is excellent.

0:51:430:51:51

It's such a different sensation.

0:51:510:51:53

I didn't really feel anything,

0:51:530:51:55

just the point at which it pulled out, it was quite a sudden thing,

0:51:550:52:00

but it wasn't anything more than that, I would have thought.

0:52:000:52:04

By changing his expectations about what he would feel,

0:52:040:52:08

Mike enabled David to release the painkillers in his brain.

0:52:080:52:12

He gave him a placebo effect,

0:52:130:52:15

not with a dummy pill or a sham surgery, but with words.

0:52:150:52:20

Hypnosis may not be the only way

0:52:220:52:24

to get a placebo effect without deception,

0:52:240:52:28

but it's certainly an excellent way to do that

0:52:280:52:31

and you can think of it as an extra strength, non-deceptive placebo.

0:52:310:52:37

It seems that something about the relationship

0:52:370:52:41

between practitioner and patient

0:52:410:52:43

lies at the heart of inducing a placebo effect without deception.

0:52:430:52:48

So, is it possible for doctors to give patients a placebo effect

0:52:540:52:59

by changing nothing more than their relationship with their patient?

0:52:590:53:03

Answering that question could help provide the key

0:53:040:53:07

to unlock our body's potential to heal itself.

0:53:070:53:12

Ted Kaptchuk set up an experiment to find out.

0:53:120:53:15

People with irritable bowel syndrome were recruited

0:53:190:53:22

to be treated with acupuncture.

0:53:220:53:24

They were divided into different groups.

0:53:240:53:27

In one group,

0:53:270:53:28

the acupuncturist's interaction with their patient was strictly limited.

0:53:280:53:33

We did not allow the practitioner to have an interaction with the patient.

0:53:330:53:37

And that meant the patient came in, the practitioner said,

0:53:430:53:46

"My name is...I've read the charts,

0:53:460:53:48

"I'm going to treat you with acupuncture.

0:53:480:53:50

"I've been asked by the research scientists not to interact, to not confuse the scientific question."

0:53:500:53:55

Hi, Mr Casey, come on in.

0:53:550:53:58

In another group, the patients were treated

0:53:590:54:02

in as caring and supportive a manner as possible.

0:54:020:54:05

We added a warm supportive relationship,

0:54:080:54:11

which included delving deeply into a patient's life,

0:54:110:54:15

how does this affect your life,

0:54:150:54:16

what's your relationship to these symptoms,

0:54:160:54:19

how does it affect your being able to have family, friends, work.

0:54:190:54:23

And tell me what kind of improvements you'd like to see,

0:54:230:54:26

so I get a good sense of that.

0:54:260:54:28

Empathy, expressing how we understood how difficult this was.

0:54:280:54:32

Some way, we had to touch the patient.

0:54:320:54:35

Thoughtful silence - we tried to have the practitioner

0:54:350:54:37

think for a moment and then ask to repeat a question

0:54:370:54:40

and some statement of confidence, "I think this is going to work."

0:54:400:54:43

I'm pretty sure these treatments will be very helpful for you,

0:54:430:54:47

and I hope they push you along to the next level.

0:54:470:54:49

All Ted was interested in was the placebo effect of this interaction -

0:54:490:54:54

so all active treatment was removed.

0:54:540:54:57

The patients would receive acupuncture

0:54:580:55:01

with needles that couldn't even puncture their skin.

0:55:010:55:04

The needle is... It looks like an acupuncture pin,

0:55:050:55:09

it's impossible to tell the difference unless you have...

0:55:090:55:12

I can barely see any difference.

0:55:120:55:14

Watch it go in.

0:55:140:55:15

See it go in.

0:55:160:55:17

And what happened is that it went up the shaft of the needle,

0:55:180:55:21

like a magic sword.

0:55:230:55:25

It's no surprise that a patient treated in a caring way

0:55:250:55:28

might feel more looked after.

0:55:280:55:30

-You feel it yet?

-I do.

-OK.

0:55:300:55:32

-But it's not bad, right?

-It's not bad.

0:55:320:55:35

But could it really make them better?

0:55:350:55:38

After all, it's just about being nice.

0:55:380:55:41

But Ted's results show that the relationship between a doctor

0:55:450:55:49

and their patient is significant.

0:55:490:55:52

With no doctor/patient relationship,

0:55:520:55:54

42% had adequate relief.

0:55:540:55:58

And on the full monty, the... everything, with doctor/patient

0:55:580:56:02

and the practitioner relationship and all the other arms

0:56:020:56:05

we got 62% reporting adequate relief.

0:56:050:56:08

What it's telling us is that a practitioner interaction

0:56:090:56:13

dramatically optimises the placebo effect.

0:56:130:56:16

Ted's study shows that a doctor can potentially create a placebo effect

0:56:190:56:25

just by changing the way they behave and the things they say.

0:56:250:56:28

It's still early days for the research at Harvard,

0:56:310:56:34

but it suggests that we can use the power of the placebo effect

0:56:340:56:39

to help make drugs and surgery more effective.

0:56:390:56:42

Placebo research is still in its infancy.

0:56:510:56:55

There's much more to learn.

0:56:550:56:57

Why do some people respond better than others?

0:56:570:57:00

Do genetics play a role?

0:57:000:57:02

What exactly does a doctor need to do to harness the placebo effect?

0:57:040:57:08

But one thing we know for sure is that it's real.

0:57:100:57:14

Even the most sceptical people now accept

0:57:150:57:18

that there is something in the placebo effect.

0:57:180:57:21

And that's a sea-change on 20 or 30 years ago where people

0:57:220:57:25

were routinely describing the placebo as an experimental artefact.

0:57:250:57:30

The placebo effect is real, quantifiable

0:57:300:57:34

and in fact you're doing quite well with an active therapy

0:57:340:57:38

if you can get as good a response as the placebo response.

0:57:380:57:41

The pills and procedures of modern medicine

0:57:410:57:45

have brought us unprecedented good health.

0:57:450:57:48

But in many cases it seems they're not acting alone.

0:57:490:57:52

The placebo effect is intertwined with everything we do in healthcare.

0:57:530:57:59

It was there from the beginning, it'll be there to the end.

0:57:590:58:03

The challenge facing researchers now

0:58:040:58:06

is to better understand the mechanisms by which it works.

0:58:060:58:10

So that ultimately we can use it

0:58:110:58:13

and make the most of the power of the placebo.

0:58:130:58:18

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