0:00:02 > 0:00:04This is a remarkable little pill.
0:00:06 > 0:00:08It comes in all shapes and sizes.
0:00:10 > 0:00:12It can relieve pain,
0:00:12 > 0:00:14treat depression,
0:00:14 > 0:00:18and has even helped ease the symptoms of Parkinson's Disease.
0:00:20 > 0:00:23And yet, it isn't a wonder drug.
0:00:23 > 0:00:26In fact, there isn't anything in it.
0:00:29 > 0:00:32As a scientist, it's unbelievable!
0:00:32 > 0:00:36These pills are placebos.
0:00:36 > 0:00:38Dummy pills. Sugar pills.
0:00:38 > 0:00:41I'm thinking, "He wants me to take sugar pills?
0:00:42 > 0:00:44"This isn't going to work."
0:00:44 > 0:00:48But the latest research is starting to show why placebos do work.
0:00:49 > 0:00:52And how you could make the most of them.
0:01:11 > 0:01:15At the home of British cycling, at the Manchester velodrome,
0:01:15 > 0:01:18some of the country's top cyclists have gathered together.
0:01:19 > 0:01:21They're elite.
0:01:21 > 0:01:24Many are national champions, past or present.
0:01:27 > 0:01:30They've been brought together by Dr Chris Beedie.
0:01:30 > 0:01:34He wants to see if he can give them some pills to help them
0:01:34 > 0:01:38do something that would normally take months of training.
0:01:38 > 0:01:43He wants to see if he can make them cycle faster than ever before.
0:01:43 > 0:01:46We're going to get all the riders onto the track
0:01:46 > 0:01:50to do a sprint time trial, to get an idea from that
0:01:50 > 0:01:52of their baseline speed,
0:01:52 > 0:01:57and then four hours later we're going to give them a couple of these.
0:01:57 > 0:02:00And we're expecting them to have an effect on their performance.
0:02:03 > 0:02:07The cyclists have been invited to take part in an experiment
0:02:07 > 0:02:11looking at the effect of legal performance-enhancing supplements.
0:02:14 > 0:02:18We're looking at testing a new ergogenic aid.
0:02:19 > 0:02:23Half of you will be getting what we'd call a standard ergogenic aid,
0:02:23 > 0:02:25which is caffeine.
0:02:25 > 0:02:27The other half will be getting caffeine,
0:02:27 > 0:02:31with some nitrate and some bicarbonate in those capsules.
0:02:31 > 0:02:34And we're expecting that to do slightly better.
0:02:35 > 0:02:38So to evaluate this we need two time trials from you,
0:02:38 > 0:02:40absolutely 100%,
0:02:40 > 0:02:43absolutely everything you've got in both time trials.
0:02:52 > 0:02:54The cyclists' baseline performance is measured
0:02:54 > 0:02:57to get a sense of their natural competitive time.
0:03:07 > 0:03:11And then - it's time for the pills.
0:03:11 > 0:03:14OK, we've got the baseline performance,
0:03:14 > 0:03:18we now are going to give them some of these and see what effect these have.
0:03:18 > 0:03:22One by one, the cyclists receive their performance-enhancing capsules
0:03:22 > 0:03:24from members of Chris' team.
0:03:24 > 0:03:27Hi, Lisa, you've been randomised today to receive the caffeine.
0:03:29 > 0:03:32Today you've been randomised to take the mixed supplement.
0:03:33 > 0:03:36Hannah, today you've been randomised to receive the pure caffeine.
0:03:37 > 0:03:40Today you've been randomised to receive the new supplement.
0:03:42 > 0:03:46But nothing about today is quite as it seems.
0:03:46 > 0:03:50Both sets of pills are exactly the same.
0:03:50 > 0:03:55The cyclists are actually taking part in a very different experiment.
0:03:56 > 0:03:59These are the capsules we're going to be using today.
0:03:59 > 0:04:02We've got a couple of red ones and a couple of red and white ones.
0:04:02 > 0:04:06They're fairly large and they look like they mean business.
0:04:06 > 0:04:08They are, however, filled with cornflour.
0:04:15 > 0:04:19Chris wants to see if the cornflour can improve the cyclists' times,
0:04:19 > 0:04:24even though they already do all they can to be as fast as possible.
0:04:25 > 0:04:29But, having raced just a couple of hours ago, the riders are tired.
0:04:30 > 0:04:34The thought of doing two in one day, it would never happen.
0:04:35 > 0:04:36You'd normally sort of race one,
0:04:36 > 0:04:40and then a day or so, you'd start again... Two in one day's going to be interesting!
0:04:43 > 0:04:47It's fair to expect that their second race of the day would be slower.
0:04:48 > 0:04:51It's time to see what the pills can do.
0:05:22 > 0:05:25Do you feel that the second ride felt easier?
0:05:25 > 0:05:29The first one, it got progressively harder during the ride.
0:05:29 > 0:05:31The second ride, after about a lap and a half out of the four laps,
0:05:31 > 0:05:35it kind of got to a point where it was hurting but then it never got any worse.
0:05:36 > 0:05:39The second ride felt better, yes.
0:05:40 > 0:05:44I went half a second quicker, which is quite a lot over that distance.
0:05:44 > 0:05:48I felt as if I was a little bit quicker second time round.
0:05:48 > 0:05:50I felt really tired before I took it.
0:05:50 > 0:05:53I think it may have started to kick in whilst I was warming up
0:05:53 > 0:05:56and I got a bit of a burst of energy and I felt ready to go again.
0:05:58 > 0:06:03In spite of the fact that the riders were tired from their earlier race,
0:06:03 > 0:06:07analysis of today's times shows that more than half of them
0:06:07 > 0:06:09were quicker with the cornflour.
0:06:15 > 0:06:18The placebo has even helped one cyclist
0:06:18 > 0:06:21to ride faster than ever before.
0:06:25 > 0:06:26It was really good,
0:06:26 > 0:06:29really surprised to go quicker in the second run.
0:06:29 > 0:06:31And a personal best as well by two tenths of a second,
0:06:31 > 0:06:35and to beat a couple of the lads that are here today that normally beat me,
0:06:35 > 0:06:36big surprise, yeah, really happy.
0:06:38 > 0:06:43- So, you did a PB, you felt the effects of the substance.- Yeah.
0:06:43 > 0:06:46Um, the capsule we gave you was a placebo.
0:06:48 > 0:06:49Oh, right, OK.
0:06:49 > 0:06:51- Really? - SHE LAUGHS
0:06:51 > 0:06:53Really? Wow.
0:06:57 > 0:07:01Today's trial is just a demonstration of what placebos can do.
0:07:03 > 0:07:06But it's typical of what Dr Beedie has found
0:07:06 > 0:07:10in over a decade of experiments with hundreds of athletes.
0:07:10 > 0:07:14Every study we've done we found a mean placebo effect.
0:07:17 > 0:07:19In sports performance generally,
0:07:19 > 0:07:23we can see improvements quite frequently of two to three per cent.
0:07:23 > 0:07:28Well, three per cent in many sports is probably the difference between
0:07:28 > 0:07:32first place in the Olympics and not being in the top ten.
0:07:32 > 0:07:34So we're talking quite a substantial difference.
0:07:34 > 0:07:37It's a little bit like your car's going a little bit faster
0:07:37 > 0:07:39but you're not using any more petrol.
0:07:39 > 0:07:43Why that's happening, however, is still open to question.
0:07:47 > 0:07:49It seems the pills that the cyclists took
0:07:49 > 0:07:52have the potential to make a real difference -
0:07:52 > 0:07:56and it's clearly nothing to do with the cornflour in them.
0:07:57 > 0:07:59So how can a pill with nothing in it
0:07:59 > 0:08:02help someone to cycle faster than ever before?
0:08:16 > 0:08:18Since the advent of modern medicine,
0:08:18 > 0:08:21placebos have been treated with scepticism.
0:08:21 > 0:08:25It's been assumed that they can do nothing.
0:08:26 > 0:08:29They've been used only as dummy pills
0:08:29 > 0:08:32that new drugs have to beat to be considered effective.
0:08:35 > 0:08:38But in recent years a number of studies have shown
0:08:38 > 0:08:41that there may be more to a placebo than we thought.
0:08:46 > 0:08:48A few years ago,
0:08:48 > 0:08:52Dr David Kallmes decided to do a rather controversial experiment.
0:08:55 > 0:08:59For 15 years, he's been fixing broken backs by injecting them
0:08:59 > 0:09:01with a special kind of surgical cement.
0:09:04 > 0:09:06We saw terrific results from the procedure,
0:09:06 > 0:09:09really amazing results from the procedure.
0:09:09 > 0:09:11But then Dr Kallmes noticed something
0:09:11 > 0:09:15that made him question how effective the procedure was.
0:09:18 > 0:09:23I was aware of some rare cases where, believe it or not,
0:09:23 > 0:09:28the wrong vertebral body was treated, for whatever reason,
0:09:28 > 0:09:30and patients seemed to get some relief from that.
0:09:30 > 0:09:36So there was some reason to suspect that there were numerous factors
0:09:36 > 0:09:40at play in the apparent effectiveness of the cement.
0:09:41 > 0:09:43He decided to do something unusual.
0:09:46 > 0:09:50He decided to put this established procedure to the test.
0:09:52 > 0:09:56He designed a trial in which some patients would be given
0:09:56 > 0:09:58the real procedure...
0:09:58 > 0:10:01and some would be given a placebo.
0:10:03 > 0:10:07But in this case, the placebo couldn't be a dummy pill -
0:10:07 > 0:10:10it would have to be a fake operation.
0:10:13 > 0:10:16There was scepticism from many people
0:10:16 > 0:10:18about whether this was worth doing.
0:10:18 > 0:10:22I recall being at a meeting and I remember being screamed at
0:10:22 > 0:10:27and then later on being called a heretic for raising the spectre
0:10:27 > 0:10:31of the placebo effect in interventional procedures.
0:10:31 > 0:10:34Nevertheless he went ahead with the trial.
0:10:34 > 0:10:38All he needed was to recruit some patients.
0:10:50 > 0:10:53A few years ago, Bonnie Anderson had an accident
0:10:53 > 0:10:55that led her to join the trial.
0:10:58 > 0:11:01Well, when I slipped on the tiled floor in the kitchen here,
0:11:01 > 0:11:04I went complete... feet went out from underneath me,
0:11:04 > 0:11:06I went flat on my back. I could not move.
0:11:06 > 0:11:09And I thought, oh, dear, I told Don, I said,
0:11:09 > 0:11:14"I'm afraid I broke my back." The pain was just very, very severe.
0:11:15 > 0:11:19I couldn't stand up straight, I'd have to hold onto something.
0:11:22 > 0:11:27She was in pain all the time, she could do very little.
0:11:27 > 0:11:29I'd help him with the dishes,
0:11:29 > 0:11:32but he did all the vacuuming, he did more of the workload.
0:11:32 > 0:11:35- That part hasn't really changed that much!- Oh, shut up!
0:11:41 > 0:11:45When Bonnie saw the doctor, a vertebral fracture was confirmed.
0:11:47 > 0:11:49She was enrolled on the trial.
0:11:51 > 0:11:55On a cold October morning, Bonnie arrived at the hospital,
0:11:55 > 0:11:56ready for her operation.
0:11:59 > 0:12:02She couldn't know whether she was having a vertebroplasty
0:12:02 > 0:12:05or the pretend procedure - the placebo.
0:12:06 > 0:12:09Dr Kallmes developed an elaborate ruse
0:12:09 > 0:12:13to ensure that patients wouldn't work out which group they were in.
0:12:15 > 0:12:19The patient was brought into the room, was given medication by vein,
0:12:19 > 0:12:23was sterilely prepped and local anaesthesia was given.
0:12:25 > 0:12:28And only after the anaesthesia was given onto the bone
0:12:28 > 0:12:32did we press the button to see whether the patient was randomised
0:12:32 > 0:12:35to the full vertebroplasty or to the placebo.
0:12:39 > 0:12:42In both cases, no matter how they were randomised,
0:12:42 > 0:12:46we then opened the cement, which has a very strong odour like nail polish remover,
0:12:46 > 0:12:49to really simulate it for everybody in the room.
0:12:49 > 0:12:51And if they were randomised to vertebroplasty,
0:12:51 > 0:12:53we then injected cement down into the bone.
0:12:55 > 0:12:57If they were randomised to placebo...
0:12:58 > 0:13:00..we opened the cement,
0:13:00 > 0:13:02we had a script that we followed...
0:13:04 > 0:13:06..we pressed on the back and said,
0:13:06 > 0:13:10"OK, ma'am, the cement is going in now, everything's going fine,
0:13:10 > 0:13:13"things are going well, few more minutes here. OK, we're all done."
0:13:13 > 0:13:17So we really simulated the procedure for the patient.
0:13:22 > 0:13:25Bonnie felt better immediately.
0:13:25 > 0:13:28The surgery did work very, very well for me.
0:13:28 > 0:13:31It did so much for me. I was really active.
0:13:34 > 0:13:37The procedure transformed her life.
0:13:44 > 0:13:48Within a week of the injection, I was able to play golf.
0:13:48 > 0:13:51I took it a little easy, but I was able to play golf almost every day.
0:13:53 > 0:13:57And I returned to some of my duties, as far as...
0:13:57 > 0:14:01Well, I don't vacuum, but as far as dishes and stuff.
0:14:01 > 0:14:03He won't say that, but it's true.
0:14:07 > 0:14:09But Bonnie didn't have the real procedure.
0:14:10 > 0:14:12She was in the placebo group.
0:14:14 > 0:14:17And what made her so interesting
0:14:17 > 0:14:20was that she'd already had a real vertebroplasty once before.
0:14:22 > 0:14:24Which meant she was uniquely able
0:14:24 > 0:14:27to compare the real thing with the placebo.
0:14:28 > 0:14:31I thought they were both so successful
0:14:31 > 0:14:35that I could go ahead and do what I wanted to do without any problem.
0:14:37 > 0:14:41And it wasn't just Bonnie that responded so well to the placebo.
0:14:42 > 0:14:47When the results of the other 130 patients on the trial came in,
0:14:47 > 0:14:48they surprised everyone.
0:14:52 > 0:14:57There was no statistically significant difference
0:14:57 > 0:14:59in degree of pain relief
0:14:59 > 0:15:03between the patients who underwent vertebroplasty and placebo,
0:15:03 > 0:15:07and more importantly there was no statistically significant difference
0:15:07 > 0:15:10in improvement in function
0:15:10 > 0:15:14between the patients who underwent vertebroplasty and placebo.
0:15:17 > 0:15:21This study and another in Australia both suggest
0:15:21 > 0:15:26that a pretend procedure can be as effective as vertebroplasty -
0:15:26 > 0:15:29which has been carried out on over a million people.
0:15:31 > 0:15:35Both the real thing and the placebo made patients better
0:15:35 > 0:15:38than if they'd received no treatment.
0:15:39 > 0:15:43So how could a pretend procedure be so effective?
0:15:49 > 0:15:54Around the world, scientists are investigating how a placebo works.
0:15:55 > 0:16:00They're trying to find out what's happening inside your body and brain
0:16:00 > 0:16:03when you experience a placebo effect.
0:16:22 > 0:16:25It's a public holiday in the Italian Alps.
0:16:25 > 0:16:27Tourists are heading up the mountain
0:16:27 > 0:16:30to spend a day skiing in the shadow of the Matterhorn.
0:16:34 > 0:16:39But, for Fabrizio Benedetti, it's just another day in the office.
0:16:42 > 0:16:46Instead of driving to the lab,
0:16:46 > 0:16:50instead of taking a bus or a train, we take a cable car.
0:16:50 > 0:16:55# On days like these
0:16:55 > 0:16:57# When skies are blue... #
0:16:57 > 0:17:01The landscape is beautiful, it's a beautiful day.
0:17:05 > 0:17:09But Fabrizio's laboratory isn't at the top of the mountain
0:17:09 > 0:17:11just for the sake of a pleasant commute.
0:17:14 > 0:17:17He's using the low oxygen levels at high altitude
0:17:17 > 0:17:21to conduct an unusual experiment.
0:17:21 > 0:17:25He's trying to find out whether a placebo effect is imagined,
0:17:25 > 0:17:30or whether somehow a placebo can cause real changes in our bodies.
0:17:32 > 0:17:35OK, so here we are inside the station.
0:17:35 > 0:17:37There are a couple of labs.
0:17:37 > 0:17:41We have a living area, we have two bedrooms, the kitchen, the bathroom.
0:17:41 > 0:17:45Italian-Swiss border is more or less here.
0:17:45 > 0:17:47We work in Switzerland, we sleep in Italy.
0:17:49 > 0:17:53For the past few years, Fabrizio has been bringing volunteers,
0:17:53 > 0:17:57like Marco, to his mountain-top laboratory to be studied.
0:17:57 > 0:18:02He's conducting an experiment to see if anything happens to people
0:18:02 > 0:18:07when they expect extra oxygen, but don't actually get it.
0:18:07 > 0:18:13So what we do is we give real oxygen or placebo oxygen -
0:18:13 > 0:18:15the tank of the oxygen is empty -
0:18:15 > 0:18:20and we compare the effect of real oxygen with placebo oxygen.
0:18:23 > 0:18:28Fabrizio gives Marco a canister of what he's told is oxygen,
0:18:28 > 0:18:31and sets him off on a 30-minute hike.
0:18:38 > 0:18:43Even mild exercise, that's pretty tiring and difficult.
0:18:45 > 0:18:47That's the reason why we are here, of course.
0:18:50 > 0:18:53Fabrizio wants to know as much as possible
0:18:53 > 0:18:57about what's going on inside Marco's body and brain.
0:18:57 > 0:18:59His heart rate, brain activity,
0:18:59 > 0:19:04and even the neurotransmitters in his system, are all being monitored.
0:19:04 > 0:19:09At this altitude, extra oxygen would be a great help.
0:19:09 > 0:19:14If there is extra oxygen, of course, the muscles get more oxygen
0:19:14 > 0:19:16so their performance improves.
0:19:29 > 0:19:30As they hike further,
0:19:30 > 0:19:35Marco is easily able to outpace Fabrizio's team of scientists.
0:19:38 > 0:19:41You can see I cannot see him any more, actually.
0:19:44 > 0:19:47But, of course, Marco doesn't have any extra oxygen.
0:19:49 > 0:19:52So, has the fake oxygen just given him
0:19:52 > 0:19:54some kind of psychological boost?
0:19:57 > 0:20:00Or has it changed something in his body?
0:20:02 > 0:20:04By analysing the data he's gathered
0:20:04 > 0:20:07from Marco and the other subjects he's studied,
0:20:07 > 0:20:09Fabrizio has the answer.
0:20:12 > 0:20:17It's all to do with the level of a neurotransmitter called PGE2.
0:20:21 > 0:20:22When we come to high altitude,
0:20:22 > 0:20:27the low oxygen levels cause our blood oxygen levels to fall.
0:20:27 > 0:20:30This makes our PGE2 levels go up.
0:20:31 > 0:20:34And that leads us to feel some of the familiar symptoms
0:20:34 > 0:20:36of altitude sickness, like pain.
0:20:39 > 0:20:42But extra oxygen can ease the problems.
0:20:42 > 0:20:47When we give oxygen, there is a dramatic decrease in PGE2.
0:20:47 > 0:20:49This is the typical response
0:20:49 > 0:20:53after oxygen administration with real oxygen.
0:20:54 > 0:20:58The lower PGE2 level that comes from giving oxygen
0:20:58 > 0:21:03helps us to feel less pain, and therefore work harder.
0:21:03 > 0:21:06But if you give someone fake oxygen
0:21:06 > 0:21:09you wouldn't expect the PGE2 levels to change.
0:21:11 > 0:21:15In this case we give fake oxygen, which means placebo oxygen,
0:21:15 > 0:21:19and there's no change in blood oxygen saturation, you see -
0:21:19 > 0:21:23we have 84% of blood oxygen saturation -
0:21:23 > 0:21:26but there's a decrease in PGE2 anyway.
0:21:28 > 0:21:35This means that this decrease is not due to oxygen in the body,
0:21:35 > 0:21:38but is due to expectation, to a placebo effect.
0:21:46 > 0:21:49The fake oxygen is causing real physiological changes
0:21:49 > 0:21:51in Fabrizio's subjects -
0:21:51 > 0:21:55decreasing their levels of PGE2,
0:21:55 > 0:22:00causing them to feel less pain, and allowing them to work harder.
0:22:00 > 0:22:04It's not imagination, it's not pure psychological effect,
0:22:04 > 0:22:07it's a real neurobiological effect.
0:22:09 > 0:22:13Somehow, fake oxygen is producing
0:22:13 > 0:22:16real chemical changes in people's bodies.
0:22:17 > 0:22:20It shows us just how real and measurable
0:22:20 > 0:22:22the placebo effect can be.
0:22:23 > 0:22:27What it doesn't tell us is how that's happening.
0:22:38 > 0:22:41Boulder, Colorado...in the foothills of the Rocky Mountains.
0:22:44 > 0:22:46Tor Wager is trying to figure out
0:22:46 > 0:22:49how a placebo can change the chemicals in our bodies.
0:22:51 > 0:22:56He's getting ready for another day inflicting mild torture on someone.
0:22:59 > 0:23:02We do the thermal pain test a lot because it's not damaging
0:23:02 > 0:23:05and it's safe, but it is painful.
0:23:07 > 0:23:11Right, Jake, come on in, you can have a seat right here.
0:23:11 > 0:23:13Tor is hoping to fool Jake into believing
0:23:13 > 0:23:18that a standard moisturiser is a powerful pain relief cream.
0:23:20 > 0:23:23He begins by applying some moisturiser to Jake's arm,
0:23:23 > 0:23:25and tells him what it is.
0:23:25 > 0:23:27This is just to have something on your skin.
0:23:27 > 0:23:32It won't provide any pain relief, and will serve as a control.
0:23:32 > 0:23:33OK.
0:23:33 > 0:23:36On a different spot, he applies some lidocaine -
0:23:36 > 0:23:41a local anaesthetic - which will dampen the pain that Jake feels.
0:23:41 > 0:23:44We already know that it blocks pain, but we're just going to look
0:23:44 > 0:23:48- and see whether it changes pain in your brain.- OK.
0:23:48 > 0:23:51And finally, there's more moisturiser.
0:23:51 > 0:23:54But Jake is told that it's also a local anaesthetic.
0:23:59 > 0:24:02We'll do the analgesic on both of these spots.
0:24:07 > 0:24:10We'll just wait just a minute for that to take effect.
0:24:11 > 0:24:15Jake will then be subjected to heat pain on the different sites
0:24:15 > 0:24:17and be asked to rate them.
0:24:17 > 0:24:20Meanwhile his brain will be scanned,
0:24:20 > 0:24:24allowing Tor to learn more about how a placebo works.
0:24:24 > 0:24:28So we're going to give you a series of your level 8 temperatures, Jake.
0:24:28 > 0:24:30And just use the trackball there, and just rate what you feel,
0:24:30 > 0:24:33moment by moment, track your pain continuously.
0:24:33 > 0:24:34OK, so we're ready to go in.
0:24:44 > 0:24:48This is the pain rating scale, he's rating his pain continuously,
0:24:48 > 0:24:53and the anchors here are no sensation to strongest imaginable sensation.
0:24:53 > 0:24:57Jake's first heat treatment is on the control area.
0:24:57 > 0:24:59All right, Jake, we've got it tuned
0:24:59 > 0:25:01and ready to go for the first task here, OK?
0:25:03 > 0:25:06With no anaesthetic, it's not a pleasant experience.
0:25:06 > 0:25:08It's going up
0:25:08 > 0:25:12and it's just above very strong.
0:25:12 > 0:25:13Oh, that's big, that's good!
0:25:13 > 0:25:17That was the control, this is with the lidocaine,
0:25:17 > 0:25:19just rate what you feel, we'll be scanning.
0:25:22 > 0:25:26On the lidocaine site, the pain is noticeably reduced.
0:25:28 > 0:25:31So with the control cream, they were between very strong
0:25:31 > 0:25:35and strongest imaginable, so they were pretty high.
0:25:35 > 0:25:37And with the actual lidocaine cream
0:25:37 > 0:25:39they were between strong and very strong,
0:25:39 > 0:25:40so there was a substantial drop.
0:25:40 > 0:25:43But how will Jake fare when the same heat is applied
0:25:43 > 0:25:46on the moisturiser that Tor has said is lidocaine?
0:25:46 > 0:25:48Last one, lidocaine number 2.
0:25:51 > 0:25:54When he felt this temperature on the control area,
0:25:54 > 0:25:58he rated his pain above very strong.
0:25:58 > 0:25:59Let's see what happens.
0:26:11 > 0:26:13Oh, this one is the lowest so far actually,
0:26:13 > 0:26:17so that trial is lower than any of his lidocaine trials actually.
0:26:18 > 0:26:22The basic conclusion is that here the placebo response for him
0:26:22 > 0:26:25is about as large as the lidocaine responses.
0:26:26 > 0:26:29OK, Jake... so how did that feel, by the way?
0:26:29 > 0:26:32- Feels less painful. - Feels less painful?- Yeah.
0:26:34 > 0:26:39So I told you before that we were applying the real lidocaine on all four sites, right?
0:26:39 > 0:26:42But actually we didn't apply the lidocaine on all the sites.
0:26:43 > 0:26:46So what we actually did is we applied the control here,
0:26:46 > 0:26:49so this is where your pain ratings were highest.
0:26:49 > 0:26:52These two were both the real lidocaine,
0:26:52 > 0:26:54- and these two were the placebo. - Interesting.
0:26:54 > 0:26:57So, knowing that, do you feel like it worked?
0:26:57 > 0:26:59Or do you feel like, um...
0:26:59 > 0:27:02- The lidocaine or the placebo? - The placebo.- Definitely, yes!
0:27:05 > 0:27:07The significance of Tor's work
0:27:07 > 0:27:10is that by scanning the brains of people as they experience
0:27:10 > 0:27:17a placebo effect, he's revealed clues about how a placebo works.
0:27:17 > 0:27:22So when we've given people a placebo treatment, what we see is the release
0:27:22 > 0:27:26of endogenous opioids, which is the brain's own morphine,
0:27:26 > 0:27:28in a number of brain areas
0:27:28 > 0:27:31including this area here which is the periaqueductal grey,
0:27:31 > 0:27:35which is really a critical site for opioid-mediated pain control.
0:27:40 > 0:27:43What that means is that the placebo effect
0:27:43 > 0:27:47is tapping into some of the same pain control circuitry
0:27:47 > 0:27:49as opiate drugs, like morphine.
0:27:52 > 0:27:54What Tor has shown
0:27:54 > 0:27:58goes to the heart of the mechanism of how a placebo works.
0:27:58 > 0:28:02A dummy pill or cream or surgery can release
0:28:02 > 0:28:06the naturally-occurring painkillers in our brains.
0:28:07 > 0:28:11And it isn't just painkillers that a placebo can activate.
0:28:16 > 0:28:21Our brains are capable of producing countless chemicals that we need -
0:28:21 > 0:28:23to stop pain or to feel it,
0:28:23 > 0:28:27to energise us or to help us sleep.
0:28:29 > 0:28:34And a placebo can mimic many of them - from aspirin to alcohol.
0:28:36 > 0:28:39The placebo effect taps into our natural pharmacy.
0:28:40 > 0:28:43Drugs work because we have receptors for the drugs,
0:28:43 > 0:28:46and that means that there's some endogenous chemicals
0:28:46 > 0:28:49that our brains are producing that act on those receptors -
0:28:49 > 0:28:54the receptors evolved to respond to those natural chemicals.
0:28:55 > 0:28:58So, a placebo can produce real results
0:28:58 > 0:29:02by tapping into the chemical systems that our bodies have evolved.
0:29:04 > 0:29:09Just like modern medicines, a placebo effect relies on chemicals -
0:29:09 > 0:29:11the chemicals in our brains.
0:29:20 > 0:29:24Scientists want to know just how much a simple sugar pill can do.
0:29:26 > 0:29:29Can it only affect conditions which rely on self-reporting -
0:29:29 > 0:29:34like pain - or could it do much more?
0:29:49 > 0:29:53Paul Pattison lives on the outskirts of Vancouver.
0:29:53 > 0:29:55It gives him easy access to the woods and mountains
0:29:55 > 0:29:57on the edge of the city.
0:29:57 > 0:30:02But 12 years ago life took a turn for the worse,
0:30:02 > 0:30:05when he started to develop some unsettling symptoms.
0:30:06 > 0:30:09I started to notice I was not... my stride wasn't right,
0:30:09 > 0:30:13and I-I-I...my doctor referred me to a podiatrist,
0:30:13 > 0:30:16thinking something was wrong with my ankle, my foot, whatever.
0:30:19 > 0:30:23So the podiatrist had me in there a couple of weeks later and he goes,
0:30:23 > 0:30:26"Oh, my gosh, you don't need a podiatrist, you need a neurologist."
0:30:27 > 0:30:30So I went back to my GP, got referred to a neurologist
0:30:30 > 0:30:35and he took one look at me and said, "OK, you have Parkinson's."
0:30:37 > 0:30:39Well, holy smoke! That was...
0:30:39 > 0:30:42that was quite traumatic, I was in tears for sure.
0:30:45 > 0:30:48It came as a complete shock to Paul and his family,
0:30:48 > 0:30:51and eventually forced him to give up his job.
0:30:54 > 0:30:59Parkinson's is caused by an inability of the brain to release dopamine.
0:31:00 > 0:31:02As well as affecting our mood,
0:31:02 > 0:31:05dopamine helps to regulate our movement.
0:31:06 > 0:31:09With medication, Paul can get the dopamine he needs
0:31:09 > 0:31:12to keep his symptoms under control.
0:31:13 > 0:31:17So I take Sinemet CR, control release, is the pink one.
0:31:17 > 0:31:22And the two white ones are 2.5mg each of Bromocriptine
0:31:22 > 0:31:26and as you see, I'm upright, I'm mobile, my shoulders are back.
0:31:31 > 0:31:35A few years ago, Parkinson's researcher Professor Jon Stoessl
0:31:35 > 0:31:39decided to test this effective medication against a placebo.
0:31:40 > 0:31:42We've always known
0:31:42 > 0:31:47that how people do when they have a serious condition
0:31:47 > 0:31:50has a lot to do with their attitude
0:31:50 > 0:31:52and that's intriguing to me.
0:31:53 > 0:31:56Paul was recruited onto Jon's trial.
0:31:56 > 0:32:01It would require him to stop taking his medication.
0:32:01 > 0:32:04Without it, even walking can be difficult.
0:32:05 > 0:32:11About a year and a half ago, I guess, I was about 50 feet from my house,
0:32:11 > 0:32:13I could literally see the front door.
0:32:13 > 0:32:17I was sitting on the sidewalk, on the kerb, and I couldn't get home.
0:32:18 > 0:32:21That was...that was something else.
0:32:22 > 0:32:26Took me about a half-hour to get home...from a hundred feet.
0:32:26 > 0:32:27Yeah.
0:32:34 > 0:32:37Paul headed into hospital for the trial,
0:32:37 > 0:32:39without having had his medication,
0:32:39 > 0:32:42his Parkinson's symptoms in full flare-up.
0:32:43 > 0:32:46And that's when they gave me this capsule.
0:32:48 > 0:32:50And they gave you a half-hour, 45 minutes, you know,
0:32:50 > 0:32:53a normal period of time for the meds to kick in.
0:32:57 > 0:33:00And boom, I was thinking, ah, this is pretty good.
0:33:00 > 0:33:04My body becomes erect, my shoulders go back
0:33:04 > 0:33:07and I needed to go to the bathroom
0:33:07 > 0:33:10so I said, "I don't need any help, I'm fine."
0:33:10 > 0:33:15And I heel-struck my way down the hall and went to the bathroom.
0:33:16 > 0:33:20But Paul hadn't been given any active medication.
0:33:20 > 0:33:21He'd been given a placebo.
0:33:26 > 0:33:27Well, I was shocked.
0:33:27 > 0:33:29There's no way I could have done that.
0:33:29 > 0:33:33I fully understand the effects of my medicine.
0:33:33 > 0:33:37So how could a nothing create those same feelings?
0:33:38 > 0:33:40Yeah, I was really shocked.
0:33:44 > 0:33:49Brain scans of patients with Parkinson's that were responding to the placebo
0:33:49 > 0:33:53helped to explain how Paul's symptoms had faded.
0:33:53 > 0:33:59This slide shows three scans all taken from the same person
0:33:59 > 0:34:01with Parkinson's disease.
0:34:01 > 0:34:04So, now you see the activity at baseline.
0:34:04 > 0:34:07When they come in with no medication,
0:34:07 > 0:34:10their Parkinson's is not well controlled,
0:34:10 > 0:34:12there's a loss of dopamine in the brain,
0:34:12 > 0:34:14so we see lots of activity here.
0:34:16 > 0:34:17With so little dopamine,
0:34:17 > 0:34:21someone with Parkinson's would be struggling to move and function.
0:34:22 > 0:34:25Now we look at the middle slide
0:34:25 > 0:34:30and this is after the person is told that they're going to get
0:34:30 > 0:34:34active drug, but in fact they receive placebo.
0:34:34 > 0:34:38And you can see a striking reduction in activity here
0:34:38 > 0:34:42which indicates that their brains have released a lot of dopamine.
0:34:44 > 0:34:48The intense red colours in the striatum area of the brain
0:34:48 > 0:34:51show how little dopamine is present at baseline.
0:34:53 > 0:34:55The decrease in the red colouring
0:34:55 > 0:35:00shows how the placebo can release dopamine just like the real drugs.
0:35:04 > 0:35:08What we found is that, in somebody with Parkinson's disease,
0:35:08 > 0:35:13a placebo can release as much dopamine as amphetamine or speed can
0:35:13 > 0:35:16in somebody with a healthy dopamine system.
0:35:16 > 0:35:18So it's a very dramatic response.
0:35:20 > 0:35:24There are physical things that change in me when I take my meds
0:35:24 > 0:35:28and I didn't think a placebo would be capable of, you know...
0:35:28 > 0:35:31There's no way - you know, how could a sugar pill or whatever,
0:35:31 > 0:35:34you know, make me feel like I had taken my Sinemet?
0:35:34 > 0:35:36I'm thrilled to death to know that I still have the ability
0:35:36 > 0:35:39on a short-term basis to produce dopamine and get going, right?
0:35:41 > 0:35:45Several studies have now shown that a placebo can ease
0:35:45 > 0:35:49the symptoms of Parkinson's - even if only in the short term.
0:35:50 > 0:35:53Once again, the placebo works
0:35:53 > 0:35:55by tapping into the brain's internal pharmacy.
0:35:57 > 0:36:00All these studies raise another intriguing question.
0:36:04 > 0:36:09For a placebo to work, why do we need to believe that it's real?
0:36:20 > 0:36:22Pull your body into the rock, that's nice.
0:36:24 > 0:36:27For Tor Wager, it's all about our expectations.
0:36:31 > 0:36:34They can make a difference to what happens in our bodies -
0:36:34 > 0:36:37and that's true whether you take a pill,
0:36:37 > 0:36:42undergo an operation or climb a mountain.
0:36:42 > 0:36:44Stand up on that back foot, Tor.
0:36:47 > 0:36:50Climbing is a dangerous sport.
0:36:50 > 0:36:55One false move, and things could go badly wrong for Tor -
0:36:55 > 0:36:58except, of course, that he's got a rope.
0:37:00 > 0:37:02And that changes everything.
0:37:02 > 0:37:06- Going right. Watch me here.- Good.
0:37:06 > 0:37:08He expects to be safe.
0:37:08 > 0:37:10Step through, beautiful, that's it.
0:37:12 > 0:37:15And yet, without his belief that everything will be OK,
0:37:15 > 0:37:17he'd be so nervous he could barely climb.
0:37:20 > 0:37:23When I was up there on the rock, my heart started beating,
0:37:23 > 0:37:27blood flow changed to my fingers, my brain's releasing opioids,
0:37:27 > 0:37:30releasing dopamine, and all those things are helping me perform,
0:37:30 > 0:37:33and they're also having various impacts on my body.
0:37:34 > 0:37:38Those impacts depend on the feeling, the knowledge that I'm safe.
0:37:38 > 0:37:41Take off that rope, it would be a completely different world -
0:37:41 > 0:37:46my heart rate would go crazy, I'd be sweating, and so forth.
0:37:48 > 0:37:53Ultimately, it's about the link between our minds and our bodies.
0:37:55 > 0:38:00Whether it's fear or hope, our thoughts and expectations
0:38:00 > 0:38:04can trigger chemical reactions that change our bodies.
0:38:06 > 0:38:10So, if we expect a placebo to do something,
0:38:10 > 0:38:15it can release chemicals in our brains and change our physiology.
0:38:19 > 0:38:21Scientists are now exploring
0:38:21 > 0:38:24just how much our expectations are capable of.
0:38:25 > 0:38:30As well as pain, they've found that placebos can alleviate conditions
0:38:30 > 0:38:33from depression to insomnia,
0:38:33 > 0:38:36nausea to attention-deficit disorder.
0:38:38 > 0:38:43And because it's all about your expectations, even the size
0:38:43 > 0:38:47and shape of a pill can make a difference to how well it works.
0:38:48 > 0:38:53Studies have shown that capsules are more effective than tablets.
0:38:54 > 0:38:57A large capsule is better than a small capsule.
0:38:57 > 0:39:02Expensive medications are more effective than cheap medications.
0:39:02 > 0:39:04Colour makes a difference -
0:39:04 > 0:39:08red pills are more effective for treating pain,
0:39:08 > 0:39:12blue pills are more effective for treating anxiety.
0:39:14 > 0:39:16Unless you happen to be male and Italian,
0:39:16 > 0:39:20in which case blue is the colour of your national football team,
0:39:20 > 0:39:25and a symbol of immense excitement, passion, and heartache.
0:39:25 > 0:39:28In that case, according to research,
0:39:28 > 0:39:32a blue pill won't help relax you - it will do the opposite.
0:39:34 > 0:39:37But there are clear limits to what placebos can do.
0:39:38 > 0:39:43They certainly won't fix a broken leg or help to shrink a tumour.
0:39:44 > 0:39:46But in the areas where they seem effective,
0:39:46 > 0:39:51scientists are beginning to wonder how we can make the most of them.
0:40:01 > 0:40:05There is, however, a problem with dummy pills and sham surgeries.
0:40:05 > 0:40:07They rely on deception.
0:40:08 > 0:40:11You're not told the truth.
0:40:11 > 0:40:15That seems to be why they work - because you think they're real.
0:40:16 > 0:40:20Obviously doctors don't want to lie to their patients.
0:40:20 > 0:40:25So how do we harness the power of the placebo effect without lying?
0:40:29 > 0:40:35It's a question that one of the most prestigious medical schools in the world is hoping to answer.
0:40:37 > 0:40:42In 2010, Harvard established a Program in Placebo Studies.
0:40:42 > 0:40:47It aims to work out how we can use the placebo effect
0:40:47 > 0:40:49to make people better.
0:40:49 > 0:40:52Ted Kaptchuk is the Director.
0:40:52 > 0:40:53In the last 15-20 years,
0:40:53 > 0:40:56there's been an explosion of research in placebo studies.
0:40:56 > 0:40:59We've learnt so much, but there's so much more to do.
0:41:01 > 0:41:05The underlying goal is how do we learn to harness it and use it
0:41:05 > 0:41:08to help people get better, healthier and stronger lives?
0:41:10 > 0:41:13Recently, Ted decided to challenge
0:41:13 > 0:41:16one of the most basic assumptions about placebos.
0:41:16 > 0:41:19He decided to conduct an experiment to see
0:41:19 > 0:41:24whether we really need to be duped for a placebo to work.
0:41:24 > 0:41:27The conventional wisdom was that you have to use either deception
0:41:27 > 0:41:30or concealment in order for a placebo to work.
0:41:30 > 0:41:35We decided to test whether or not you could still get a placebo effect
0:41:35 > 0:41:38if you gave a person a placebo and told them it was a placebo.
0:41:40 > 0:41:45Linda Buonanno has suffered from irritable bowel syndrome for 16 years.
0:41:45 > 0:41:48At times, the symptoms are bad enough
0:41:48 > 0:41:50that she doesn't want to leave home.
0:41:50 > 0:41:53Along with 80 other sufferers of IBS,
0:41:53 > 0:41:56she was recruited onto Ted's trial.
0:41:56 > 0:42:00She was given some pills and told they were a placebo,
0:42:00 > 0:42:03with no active ingredient,
0:42:03 > 0:42:08but that they might work, thanks to her own self-healing processes.
0:42:08 > 0:42:10I said, "What? A placebo?"
0:42:10 > 0:42:13Because I'd just finished college as a medical assistant
0:42:13 > 0:42:16and I'm thinking, "He wants me to take sugar pills?
0:42:16 > 0:42:18"This isn't going to work."
0:42:18 > 0:42:22But I said I'd do it, so I went home, I started taking 'em...
0:42:33 > 0:42:37..and after three days I realised I wasn't in any pain any more.
0:42:39 > 0:42:41I didn't have any intestinal pain,
0:42:41 > 0:42:45I didn't keep running to the bathroom or anything like that.
0:42:45 > 0:42:49I didn't have any stomach cramps, I had nothing, all the symptoms,
0:42:49 > 0:42:51the severe symptoms I had, were gone.
0:42:54 > 0:42:56I thought, no, this is not happening,
0:42:56 > 0:43:00this can't be, a sugar pill does not get rid of the problems, right?
0:43:02 > 0:43:05Linda wasn't the only study participant who reported
0:43:05 > 0:43:09improved symptoms from a pill she knew to be inactive.
0:43:10 > 0:43:12I was taken aback when we finished the trial
0:43:12 > 0:43:15and our statisticians showed us the results
0:43:15 > 0:43:17and it was much stronger than we expected.
0:43:17 > 0:43:2062 per cent said they got adequate relief
0:43:20 > 0:43:22from being on the placebo pill.
0:43:22 > 0:43:26People who got nothing, I think it was around 30%, said they had adequate relief,
0:43:26 > 0:43:29so there's a real big difference, it was easy to detect.
0:43:30 > 0:43:33But the study - and the supply of placebo pills -
0:43:33 > 0:43:35only lasted a few weeks.
0:43:36 > 0:43:40When the pills ran out, Linda's problems returned.
0:43:41 > 0:43:44It was three weeks, I think it was, and everything was fine,
0:43:44 > 0:43:47and then all of a sudden I'm not taking 'em any more
0:43:47 > 0:43:49and all the symptoms came back.
0:43:49 > 0:43:51It was horrible, it was like,
0:43:51 > 0:43:53oh, man, I've got to suffer with this again?
0:43:58 > 0:44:02Linda decided to try and buy some more placebo pills.
0:44:05 > 0:44:07I tried to go to one of the health food stores
0:44:07 > 0:44:10to buy the placebo pills but they didn't have them.
0:44:14 > 0:44:16The fella in the store was, you know,
0:44:16 > 0:44:19thought it was kind of odd why I would be asking for placebo pills.
0:44:19 > 0:44:21They had nothing else that would replace it,
0:44:21 > 0:44:24so I couldn't do anything, I was really disappointed.
0:44:24 > 0:44:29Well, several patients actually asked us for more placebo pills.
0:44:29 > 0:44:32Our Ethics Committee only gave us permission for three weeks
0:44:32 > 0:44:35of treating people with placebo pills, and, as you can imagine,
0:44:35 > 0:44:41I don't believe they're listed as a labelled drug in the United States.
0:44:41 > 0:44:43So we weren't able to prescribe after that.
0:44:43 > 0:44:47It's hard to know why Linda's symptoms disappeared,
0:44:47 > 0:44:52when she took something that she knew was chemically worthless.
0:44:53 > 0:44:57The study only looked at whether it would work, not why.
0:44:57 > 0:44:59But Ted has a theory.
0:45:00 > 0:45:06What I think happened is that just seeing our study physician...
0:45:08 > 0:45:13..taking pills two times a day, in some way your body feels,
0:45:13 > 0:45:16recognises, moves in a way that's moving towards health.
0:45:16 > 0:45:20This is the body knowing something that's beyond their ability
0:45:20 > 0:45:23to consciously be aware of.
0:45:23 > 0:45:26I don't understand it, I don't know why and probably never will.
0:45:26 > 0:45:30But there's something. I think I'm wishing for a cure
0:45:30 > 0:45:33and I'm wishing for something to make this all disappear.
0:45:33 > 0:45:36I think if I wish hard enough, it'll work, I guess.
0:45:39 > 0:45:42Exactly why the pills worked remains a mystery.
0:45:42 > 0:45:47And a small, short-term study like this certainly doesn't mean
0:45:47 > 0:45:51that we can simply replace real drugs with placebos.
0:45:51 > 0:45:53But it does call into question
0:45:53 > 0:45:56the fundamental assumption about placebos -
0:45:56 > 0:46:00the idea that we need to be duped for them to work.
0:46:02 > 0:46:05At Harvard, other scientists are searching for ways
0:46:05 > 0:46:09that we can use the power of the placebo without deception.
0:46:09 > 0:46:14One of Ted's colleagues has studied something you might have thought
0:46:14 > 0:46:17wouldn't have anything to do with placebos.
0:46:17 > 0:46:19And that is hypnosis.
0:46:20 > 0:46:24There's a lot of overlap between the idea of placebo
0:46:24 > 0:46:26and the idea of hypnosis.
0:46:27 > 0:46:29Separate the two index fingers.
0:46:29 > 0:46:32And lift your hands and your arms up.
0:46:32 > 0:46:38First of all, they're all based on belief, expectation and suggestion.
0:46:40 > 0:46:42A hypnotic induction is a procedure
0:46:42 > 0:46:46that has no active ingredient except for the person's belief
0:46:46 > 0:46:49and understanding about what it is supposed to do.
0:46:52 > 0:46:55Mike Gow is a dentist and a hypnotist.
0:46:56 > 0:46:59He's preparing David for a major procedure.
0:46:59 > 0:47:02He's going to extract his wisdom tooth.
0:47:04 > 0:47:08So, as you can see from his X-ray, a lower wisdom tooth never developed
0:47:08 > 0:47:11in the first place and that's why the upper tooth is actually
0:47:11 > 0:47:14erupting down into the space where that tooth would've been.
0:47:14 > 0:47:17When that happens, the tooth starts rubbing into the cheek,
0:47:17 > 0:47:19it starts biting down on the gum below,
0:47:19 > 0:47:22it also becomes very difficult for David to clean,
0:47:22 > 0:47:25and actually he's got some decay in this tooth,
0:47:25 > 0:47:29so almost impossible to get in to do a standard filling or restoration,
0:47:29 > 0:47:33and the tooth is in danger of breaking down and decaying further.
0:47:33 > 0:47:36Normally, removing a wisdom tooth would require
0:47:36 > 0:47:39the injection of a strong local anaesthetic.
0:47:39 > 0:47:42But David doesn't want one.
0:47:42 > 0:47:44I don't like getting the injections
0:47:44 > 0:47:46and having the numb mouth afterwards.
0:47:46 > 0:47:51So I had the opportunity to have hypnosis as a treatment
0:47:51 > 0:47:55for getting the wisdom tooth removed and I thought I'd give it a go.
0:47:58 > 0:48:02David is having no pharmacological anaesthetic today.
0:48:02 > 0:48:05He's not taking anything, he's not having any injections,
0:48:05 > 0:48:09this is going to be just hypnosis. This is the plan, of course.
0:48:09 > 0:48:12If we need to use anaesthetic, then we have it.
0:48:12 > 0:48:16The only active ingredient in David's pain relief will be
0:48:16 > 0:48:19the way Mike interacts with him -
0:48:19 > 0:48:21his hypnotic induction.
0:48:23 > 0:48:27Just notice this wave of relaxation now,
0:48:27 > 0:48:33more and more in control of your thoughts and feelings,
0:48:33 > 0:48:35calmer and calmer.
0:48:37 > 0:48:39And if I lift the left hand all the way up...
0:48:41 > 0:48:47The act of inducing hypnosis is a way of giving the person
0:48:47 > 0:48:50permission, disinhibiting them,
0:48:50 > 0:48:55so that they can now believe in their own abilities to block pain,
0:48:55 > 0:48:57to experience things differently.
0:48:58 > 0:49:03Just notice how the index finger and thumb just feel kind of dull
0:49:03 > 0:49:05and insensitive, don't they?
0:49:06 > 0:49:07Yeah?
0:49:08 > 0:49:12Are you happy now to transfer that feeling around the tooth?
0:49:14 > 0:49:16Cold...
0:49:16 > 0:49:18dull, and insensitive.
0:49:26 > 0:49:29David's wisdom tooth is firmly encased
0:49:29 > 0:49:31in the bone that surrounds it.
0:49:31 > 0:49:35Mike's first job is to gradually enlarge the socket.
0:49:38 > 0:49:42DISTORTED: And just notice now, as you allow the mouth to open,
0:49:42 > 0:49:45just feeling that pressure.
0:49:45 > 0:49:48Relaxed...
0:49:50 > 0:49:51..and comfortable.
0:49:51 > 0:49:53Throughout the procedure,
0:49:53 > 0:49:58David has been told to rate his pain on a zero to ten scale.
0:49:58 > 0:50:00And just write down a wee number now.
0:50:01 > 0:50:03A zero, that's excellent.
0:50:07 > 0:50:10As you allow the mouth to open again,
0:50:10 > 0:50:14just pushing and pressure,
0:50:14 > 0:50:18comfortable...sensations.
0:50:19 > 0:50:23Again, just write down any little number.
0:50:23 > 0:50:25A one.
0:50:27 > 0:50:29Clearly, David's pain scores aren't low
0:50:29 > 0:50:32because of any painkilling drugs he's received.
0:50:32 > 0:50:37It's his own internal painkilling systems that are working -
0:50:37 > 0:50:41the same as those that can be activated by a placebo.
0:50:41 > 0:50:46You might think of hypnosis as a procedure that allows people
0:50:46 > 0:50:52to turn on their own ability to produce a placebo effect.
0:50:53 > 0:50:56Having widened the socket sufficiently,
0:50:56 > 0:50:58Mike is ready for the critical moment -
0:50:58 > 0:51:02tearing the tooth from the ligament that holds it in place.
0:51:02 > 0:51:04Calm...
0:51:04 > 0:51:06control.
0:51:18 > 0:51:20Eyes open. Wide awake.
0:51:20 > 0:51:22That was awesome. Very well done.
0:51:24 > 0:51:27Good. So, the final moment of removing the tooth,
0:51:27 > 0:51:29there's a lot of pressure,
0:51:29 > 0:51:33and I'd be interested to know what number you were at.
0:51:33 > 0:51:36It was...probably a four-ish.
0:51:36 > 0:51:39- About a four. - In the final moment, yeah.
0:51:39 > 0:51:43Without any form of pain relief, I would expect it to be an 8 or a 9,
0:51:43 > 0:51:51without anything at all, so I think a number 4 is excellent.
0:51:51 > 0:51:53It's such a different sensation.
0:51:53 > 0:51:55I didn't really feel anything,
0:51:55 > 0:52:00just the point at which it pulled out, it was quite a sudden thing,
0:52:00 > 0:52:04but it wasn't anything more than that, I would have thought.
0:52:04 > 0:52:08By changing his expectations about what he would feel,
0:52:08 > 0:52:12Mike enabled David to release the painkillers in his brain.
0:52:13 > 0:52:15He gave him a placebo effect,
0:52:15 > 0:52:20not with a dummy pill or a sham surgery, but with words.
0:52:22 > 0:52:24Hypnosis may not be the only way
0:52:24 > 0:52:28to get a placebo effect without deception,
0:52:28 > 0:52:31but it's certainly an excellent way to do that
0:52:31 > 0:52:37and you can think of it as an extra strength, non-deceptive placebo.
0:52:37 > 0:52:41It seems that something about the relationship
0:52:41 > 0:52:43between practitioner and patient
0:52:43 > 0:52:48lies at the heart of inducing a placebo effect without deception.
0:52:54 > 0:52:59So, is it possible for doctors to give patients a placebo effect
0:52:59 > 0:53:03by changing nothing more than their relationship with their patient?
0:53:04 > 0:53:07Answering that question could help provide the key
0:53:07 > 0:53:12to unlock our body's potential to heal itself.
0:53:12 > 0:53:15Ted Kaptchuk set up an experiment to find out.
0:53:19 > 0:53:22People with irritable bowel syndrome were recruited
0:53:22 > 0:53:24to be treated with acupuncture.
0:53:24 > 0:53:27They were divided into different groups.
0:53:27 > 0:53:28In one group,
0:53:28 > 0:53:33the acupuncturist's interaction with their patient was strictly limited.
0:53:33 > 0:53:37We did not allow the practitioner to have an interaction with the patient.
0:53:43 > 0:53:46And that meant the patient came in, the practitioner said,
0:53:46 > 0:53:48"My name is...I've read the charts,
0:53:48 > 0:53:50"I'm going to treat you with acupuncture.
0:53:50 > 0:53:55"I've been asked by the research scientists not to interact, to not confuse the scientific question."
0:53:55 > 0:53:58Hi, Mr Casey, come on in.
0:53:59 > 0:54:02In another group, the patients were treated
0:54:02 > 0:54:05in as caring and supportive a manner as possible.
0:54:08 > 0:54:11We added a warm supportive relationship,
0:54:11 > 0:54:15which included delving deeply into a patient's life,
0:54:15 > 0:54:16how does this affect your life,
0:54:16 > 0:54:19what's your relationship to these symptoms,
0:54:19 > 0:54:23how does it affect your being able to have family, friends, work.
0:54:23 > 0:54:26And tell me what kind of improvements you'd like to see,
0:54:26 > 0:54:28so I get a good sense of that.
0:54:28 > 0:54:32Empathy, expressing how we understood how difficult this was.
0:54:32 > 0:54:35Some way, we had to touch the patient.
0:54:35 > 0:54:37Thoughtful silence - we tried to have the practitioner
0:54:37 > 0:54:40think for a moment and then ask to repeat a question
0:54:40 > 0:54:43and some statement of confidence, "I think this is going to work."
0:54:43 > 0:54:47I'm pretty sure these treatments will be very helpful for you,
0:54:47 > 0:54:49and I hope they push you along to the next level.
0:54:49 > 0:54:54All Ted was interested in was the placebo effect of this interaction -
0:54:54 > 0:54:57so all active treatment was removed.
0:54:58 > 0:55:01The patients would receive acupuncture
0:55:01 > 0:55:04with needles that couldn't even puncture their skin.
0:55:05 > 0:55:09The needle is... It looks like an acupuncture pin,
0:55:09 > 0:55:12it's impossible to tell the difference unless you have...
0:55:12 > 0:55:14I can barely see any difference.
0:55:14 > 0:55:15Watch it go in.
0:55:16 > 0:55:17See it go in.
0:55:18 > 0:55:21And what happened is that it went up the shaft of the needle,
0:55:23 > 0:55:25like a magic sword.
0:55:25 > 0:55:28It's no surprise that a patient treated in a caring way
0:55:28 > 0:55:30might feel more looked after.
0:55:30 > 0:55:32- You feel it yet?- I do.- OK.
0:55:32 > 0:55:35- But it's not bad, right? - It's not bad.
0:55:35 > 0:55:38But could it really make them better?
0:55:38 > 0:55:41After all, it's just about being nice.
0:55:45 > 0:55:49But Ted's results show that the relationship between a doctor
0:55:49 > 0:55:52and their patient is significant.
0:55:52 > 0:55:54With no doctor/patient relationship,
0:55:54 > 0:55:5842% had adequate relief.
0:55:58 > 0:56:02And on the full monty, the... everything, with doctor/patient
0:56:02 > 0:56:05and the practitioner relationship and all the other arms
0:56:05 > 0:56:08we got 62% reporting adequate relief.
0:56:09 > 0:56:13What it's telling us is that a practitioner interaction
0:56:13 > 0:56:16dramatically optimises the placebo effect.
0:56:19 > 0:56:25Ted's study shows that a doctor can potentially create a placebo effect
0:56:25 > 0:56:28just by changing the way they behave and the things they say.
0:56:31 > 0:56:34It's still early days for the research at Harvard,
0:56:34 > 0:56:39but it suggests that we can use the power of the placebo effect
0:56:39 > 0:56:42to help make drugs and surgery more effective.
0:56:51 > 0:56:55Placebo research is still in its infancy.
0:56:55 > 0:56:57There's much more to learn.
0:56:57 > 0:57:00Why do some people respond better than others?
0:57:00 > 0:57:02Do genetics play a role?
0:57:04 > 0:57:08What exactly does a doctor need to do to harness the placebo effect?
0:57:10 > 0:57:14But one thing we know for sure is that it's real.
0:57:15 > 0:57:18Even the most sceptical people now accept
0:57:18 > 0:57:21that there is something in the placebo effect.
0:57:22 > 0:57:25And that's a sea-change on 20 or 30 years ago where people
0:57:25 > 0:57:30were routinely describing the placebo as an experimental artefact.
0:57:30 > 0:57:34The placebo effect is real, quantifiable
0:57:34 > 0:57:38and in fact you're doing quite well with an active therapy
0:57:38 > 0:57:41if you can get as good a response as the placebo response.
0:57:41 > 0:57:45The pills and procedures of modern medicine
0:57:45 > 0:57:48have brought us unprecedented good health.
0:57:49 > 0:57:52But in many cases it seems they're not acting alone.
0:57:53 > 0:57:59The placebo effect is intertwined with everything we do in healthcare.
0:57:59 > 0:58:03It was there from the beginning, it'll be there to the end.
0:58:04 > 0:58:06The challenge facing researchers now
0:58:06 > 0:58:10is to better understand the mechanisms by which it works.
0:58:11 > 0:58:13So that ultimately we can use it
0:58:13 > 0:58:18and make the most of the power of the placebo.