Horizon (1964) s53e04 Episode Script
The Power of the Placebo
1 This is a remarkable little pill.
It comes in all shapes and sizes.
It can relieve pain, treat depression, and has even helped ease the symptoms of Parkinson's Disease.
And yet, it isn't a wonder drug.
In fact, there isn't anything in it.
As a scientist, it's unbelievable! These pills are placebos.
Dummy pills.
Sugar pills.
I'm thinking, "He wants me to take sugar pills? "This isn't going to work.
" But the latest research is starting to show why placebos do work.
And how you could make the most of them.
At the home of British cycling, at the Manchester velodrome, some of the country's top cyclists have gathered together.
They're elite.
Many are national champions, past or present.
They've been brought together by Dr Chris Beedie.
He wants to see if he can give them some pills to help them do something that would normally take months of training.
He wants to see if he can make them cycle faster than ever before.
We're going to get all the riders onto the track to do a sprint time trial, to get an idea from that of their baseline speed, and then four hours later we're going to give them a couple of these.
And we're expecting them to have an effect on their performance.
The cyclists have been invited to take part in an experiment looking at the effect of legal performance-enhancing supplements.
We're looking at testing a new ergogenic aid.
Half of you will be getting what we'd call a standard ergogenic aid, which is caffeine.
The other half will be getting caffeine, with some nitrate and some bicarbonate in those capsules.
And we're expecting that to do slightly better.
So to evaluate this we need two time trials from you, absolutely 100%, absolutely everything you've got in both time trials.
The cyclists' baseline performance is measured to get a sense of their natural competitive time.
And then - it's time for the pills.
OK, we've got the baseline performance, we now are going to give them some of these and see what effect these have.
One by one, the cyclists receive their performance-enhancing capsules from members of Chris' team.
Hi, Lisa, you've been randomised today to receive the caffeine.
Today you've been randomised to take the mixed supplement.
Hannah, today you've been randomised to receive the pure caffeine.
Today you've been randomised to receive the new supplement.
But nothing about today is quite as it seems.
Both sets of pills are exactly the same.
The cyclists are actually taking part in a very different experiment.
These are the capsules we're going to be using today.
We've got a couple of red ones and a couple of red and white ones.
They're fairly large and they look like they mean business.
They are, however, filled with cornflour.
Chris wants to see if the cornflour can improve the cyclists' times, even though they already do all they can to be as fast as possible.
But, having raced just a couple of hours ago, the riders are tired.
The thought of doing two in one day, it would never happen.
You'd normally sort of race one, and then a day or so, you'd start again Two in one day's going to be interesting! It's fair to expect that their second race of the day would be slower.
It's time to see what the pills can do.
Do you feel that the second ride felt easier? The first one, it got progressively harder during the ride.
The second ride, after about a lap and a half out of the four laps, it kind of got to a point where it was hurting but then it never got any worse.
The second ride felt better, yes.
I went half a second quicker, which is quite a lot over that distance.
I felt as if I was a little bit quicker second time round.
I felt really tired before I took it.
I think it may have started to kick in whilst I was warming up and I got a bit of a burst of energy and I felt ready to go again.
In spite of the fact that the riders were tired from their earlier race, analysis of today's times shows that more than half of them were quicker with the cornflour.
The placebo has even helped one cyclist to ride faster than ever before.
It was really good, really surprised to go quicker in the second run.
And a personal best as well by two tenths of a second, and to beat a couple of the lads that are here today that normally beat me, big surprise, yeah, really happy.
So, you did a PB, you felt the effects of the substance.
Yeah.
Um, the capsule we gave you was a placebo.
Oh, right, OK.
Really? SHE LAUGHS Really? Wow.
Today's trial is just a demonstration of what placebos can do.
But it's typical of what Dr Beedie has found in over a decade of experiments with hundreds of athletes.
Every study we've done we found a mean placebo effect.
In sports performance generally, we can see improvements quite frequently of two to three per cent.
Well, three per cent in many sports is probably the difference between first place in the Olympics and not being in the top ten.
So we're talking quite a substantial difference.
It's a little bit like your car's going a little bit faster but you're not using any more petrol.
Why that's happening, however, is still open to question.
It seems the pills that the cyclists took have the potential to make a real difference - and it's clearly nothing to do with the cornflour in them.
So how can a pill with nothing in it help someone to cycle faster than ever before? Since the advent of modern medicine, placebos have been treated with scepticism.
It's been assumed that they can do nothing.
They've been used only as dummy pills that new drugs have to beat to be considered effective.
But in recent years a number of studies have shown that there may be more to a placebo than we thought.
A few years ago, Dr David Kallmes decided to do a rather controversial experiment.
For 15 years, he's been fixing broken backs by injecting them with a special kind of surgical cement.
We saw terrific results from the procedure, really amazing results from the procedure.
But then Dr Kallmes noticed something that made him question how effective the procedure was.
I was aware of some rare cases where, believe it or not, the wrong vertebral body was treated, for whatever reason, and patients seemed to get some relief from that.
So there was some reason to suspect that there were numerous factors at play in the apparent effectiveness of the cement.
He decided to do something unusual.
He decided to put this established procedure to the test.
He designed a trial in which some patients would be given the real procedure and some would be given a placebo.
But in this case, the placebo couldn't be a dummy pill - it would have to be a fake operation.
There was scepticism from many people about whether this was worth doing.
I recall being at a meeting and I remember being screamed at and then later on being called a heretic for raising the spectre of the placebo effect in interventional procedures.
Nevertheless he went ahead with the trial.
All he needed was to recruit some patients.
A few years ago, Bonnie Anderson had an accident that led her to join the trial.
Well, when I slipped on the tiled floor in the kitchen here, I went complete feet went out from underneath me, I went flat on my back.
I could not move.
And I thought, oh, dear, I told Don, I said, "I'm afraid I broke my back.
" The pain was just very, very severe.
I couldn't stand up straight, I'd have to hold onto something.
She was in pain all the time, she could do very little.
I'd help him with the dishes, but he did all the vacuuming, he did more of the workload.
That part hasn't really changed that much! Oh, shut up! When Bonnie saw the doctor, a vertebral fracture was confirmed.
She was enrolled on the trial.
On a cold October morning, Bonnie arrived at the hospital, ready for her operation.
She couldn't know whether she was having a vertebroplasty or the pretend procedure - the placebo.
Dr Kallmes developed an elaborate ruse to ensure that patients wouldn't work out which group they were in.
The patient was brought into the room, was given medication by vein, was sterilely prepped and local anaesthesia was given.
And only after the anaesthesia was given onto the bone did we press the button to see whether the patient was randomised to the full vertebroplasty or to the placebo.
In both cases, no matter how they were randomised, we then opened the cement, which has a very strong odour like nail polish remover, to really simulate it for everybody in the room.
And if they were randomised to vertebroplasty, we then injected cement down into the bone.
If they were randomised to placebo .
.
we opened the cement, we had a script that we followed .
.
we pressed on the back and said, "OK, ma'am, the cement is going in now, everything's going fine, "things are going well, few more minutes here.
OK, we're all done.
" So we really simulated the procedure for the patient.
Bonnie felt better immediately.
The surgery did work very, very well for me.
It did so much for me.
I was really active.
The procedure transformed her life.
Within a week of the injection, I was able to play golf.
I took it a little easy, but I was able to play golf almost every day.
And I returned to some of my duties, as far as Well, I don't vacuum, but as far as dishes and stuff.
He won't say that, but it's true.
But Bonnie didn't have the real procedure.
She was in the placebo group.
And what made her so interesting was that she'd already had a real vertebroplasty once before.
Which meant she was uniquely able to compare the real thing with the placebo.
I thought they were both so successful that I could go ahead and do what I wanted to do without any problem.
And it wasn't just Bonnie that responded so well to the placebo.
When the results of the other 130 patients on the trial came in, they surprised everyone.
There was no statistically significant difference in degree of pain relief between the patients who underwent vertebroplasty and placebo, and more importantly there was no statistically significant difference in improvement in function between the patients who underwent vertebroplasty and placebo.
This study and another in Australia both suggest that a pretend procedure can be as effective as vertebroplasty - which has been carried out on over a million people.
Both the real thing and the placebo made patients better than if they'd received no treatment.
So how could a pretend procedure be so effective? Around the world, scientists are investigating how a placebo works.
They're trying to find out what's happening inside your body and brain when you experience a placebo effect.
It's a public holiday in the Italian Alps.
Tourists are heading up the mountain to spend a day skiing in the shadow of the Matterhorn.
But, for Fabrizio Benedetti, it's just another day in the office.
Instead of driving to the lab, instead of taking a bus or a train, we take a cable car.
On days like these When skies are blue The landscape is beautiful, it's a beautiful day.
But Fabrizio's laboratory isn't at the top of the mountain just for the sake of a pleasant commute.
He's using the low oxygen levels at high altitude to conduct an unusual experiment.
He's trying to find out whether a placebo effect is imagined, or whether somehow a placebo can cause real changes in our bodies.
OK, so here we are inside the station.
There are a couple of labs.
We have a living area, we have two bedrooms, the kitchen, the bathroom.
Italian-Swiss border is more or less here.
We work in Switzerland, we sleep in Italy.
For the past few years, Fabrizio has been bringing volunteers, like Marco, to his mountain-top laboratory to be studied.
He's conducting an experiment to see if anything happens to people when they expect extra oxygen, but don't actually get it.
So what we do is we give real oxygen or placebo oxygen - the tank of the oxygen is empty - and we compare the effect of real oxygen with placebo oxygen.
Fabrizio gives Marco a canister of what he's told is oxygen, and sets him off on a 30-minute hike.
Even mild exercise, that's pretty tiring and difficult.
That's the reason why we are here, of course.
Fabrizio wants to know as much as possible about what's going on inside Marco's body and brain.
His heart rate, brain activity, and even the neurotransmitters in his system, are all being monitored.
At this altitude, extra oxygen would be a great help.
If there is extra oxygen, of course, the muscles get more oxygen so their performance improves.
As they hike further, Marco is easily able to outpace Fabrizio's team of scientists.
You can see I cannot see him any more, actually.
But, of course, Marco doesn't have any extra oxygen.
So, has the fake oxygen just given him some kind of psychological boost? Or has it changed something in his body? By analysing the data he's gathered from Marco and the other subjects he's studied, Fabrizio has the answer.
It's all to do with the level of a neurotransmitter called PGE2.
When we come to high altitude, the low oxygen levels cause our blood oxygen levels to fall.
This makes our PGE2 levels go up.
And that leads us to feel some of the familiar symptoms of altitude sickness, like pain.
But extra oxygen can ease the problems.
When we give oxygen, there is a dramatic decrease in PGE2.
This is the typical response after oxygen administration with real oxygen.
The lower PGE2 level that comes from giving oxygen helps us to feel less pain, and therefore work harder.
But if you give someone fake oxygen you wouldn't expect the PGE2 levels to change.
In this case we give fake oxygen, which means placebo oxygen, and there's no change in blood oxygen saturation, you see - we have 84% of blood oxygen saturation - but there's a decrease in PGE2 anyway.
This means that this decrease is not due to oxygen in the body, but is due to expectation, to a placebo effect.
The fake oxygen is causing real physiological changes in Fabrizio's subjects - decreasing their levels of PGE2, causing them to feel less pain, and allowing them to work harder.
It's not imagination, it's not pure psychological effect, it's a real neurobiological effect.
Somehow, fake oxygen is producing real chemical changes in people's bodies.
It shows us just how real and measurable the placebo effect can be.
What it doesn't tell us is how that's happening.
Boulder, Coloradoin the foothills of the Rocky Mountains.
Tor Wager is trying to figure out how a placebo can change the chemicals in our bodies.
He's getting ready for another day inflicting mild torture on someone.
We do the thermal pain test a lot because it's not damaging and it's safe, but it is painful.
Right, Jake, come on in, you can have a seat right here.
Tor is hoping to fool Jake into believing that a standard moisturiser is a powerful pain relief cream.
He begins by applying some moisturiser to Jake's arm, and tells him what it is.
This is just to have something on your skin.
It won't provide any pain relief, and will serve as a control.
OK.
On a different spot, he applies some lidocaine - a local anaesthetic - which will dampen the pain that Jake feels.
We already know that it blocks pain, but we're just going to look and see whether it changes pain in your brain.
OK.
And finally, there's more moisturiser.
But Jake is told that it's also a local anaesthetic.
We'll do the analgesic on both of these spots.
We'll just wait just a minute for that to take effect.
Jake will then be subjected to heat pain on the different sites and be asked to rate them.
Meanwhile his brain will be scanned, allowing Tor to learn more about how a placebo works.
So we're going to give you a series of your level 8 temperatures, Jake.
And just use the trackball there, and just rate what you feel, moment by moment, track your pain continuously.
OK, so we're ready to go in.
This is the pain rating scale, he's rating his pain continuously, and the anchors here are no sensation to strongest imaginable sensation.
Jake's first heat treatment is on the control area.
All right, Jake, we've got it tuned and ready to go for the first task here, OK? With no anaesthetic, it's not a pleasant experience.
It's going up and it's just above very strong.
Oh, that's big, that's good! That was the control, this is with the lidocaine, just rate what you feel, we'll be scanning.
On the lidocaine site, the pain is noticeably reduced.
So with the control cream, they were between very strong and strongest imaginable, so they were pretty high.
And with the actual lidocaine cream they were between strong and very strong, so there was a substantial drop.
But how will Jake fare when the same heat is applied on the moisturiser that Tor has said is lidocaine? Last one, lidocaine number 2.
When he felt this temperature on the control area, he rated his pain above very strong.
Let's see what happens.
Oh, this one is the lowest so far actually, so that trial is lower than any of his lidocaine trials actually.
The basic conclusion is that here the placebo response for him is about as large as the lidocaine responses.
OK, Jake so how did that feel, by the way? Feels less painful.
Feels less painful? Yeah.
So I told you before that we were applying the real lidocaine on all four sites, right? But actually we didn't apply the lidocaine on all the sites.
So what we actually did is we applied the control here, so this is where your pain ratings were highest.
These two were both the real lidocaine, and these two were the placebo.
Interesting.
So, knowing that, do you feel like it worked? Or do you feel like, um The lidocaine or the placebo? The placebo.
Definitely, yes! The significance of Tor's work is that by scanning the brains of people as they experience a placebo effect, he's revealed clues about how a placebo works.
So when we've given people a placebo treatment, what we see is the release of endogenous opioids, which is the brain's own morphine, in a number of brain areas including this area here which is the periaqueductal grey, which is really a critical site for opioid-mediated pain control.
What that means is that the placebo effect is tapping into some of the same pain control circuitry as opiate drugs, like morphine.
What Tor has shown goes to the heart of the mechanism of how a placebo works.
A dummy pill or cream or surgery can release the naturally-occurring painkillers in our brains.
And it isn't just painkillers that a placebo can activate.
Our brains are capable of producing countless chemicals that we need - to stop pain or to feel it, to energise us or to help us sleep.
And a placebo can mimic many of them - from aspirin to alcohol.
The placebo effect taps into our natural pharmacy.
Drugs work because we have receptors for the drugs, and that means that there's some endogenous chemicals that our brains are producing that act on those receptors - the receptors evolved to respond to those natural chemicals.
So, a placebo can produce real results by tapping into the chemical systems that our bodies have evolved.
Just like modern medicines, a placebo effect relies on chemicals - the chemicals in our brains.
Scientists want to know just how much a simple sugar pill can do.
Can it only affect conditions which rely on self-reporting - like pain - or could it do much more? Paul Pattison lives on the outskirts of Vancouver.
It gives him easy access to the woods and mountains on the edge of the city.
But 12 years ago life took a turn for the worse, when he started to develop some unsettling symptoms.
I started to notice I was not my stride wasn't right, and I-I-Imy doctor referred me to a podiatrist, thinking something was wrong with my ankle, my foot, whatever.
So the podiatrist had me in there a couple of weeks later and he goes, "Oh, my gosh, you don't need a podiatrist, you need a neurologist.
" So I went back to my GP, got referred to a neurologist and he took one look at me and said, "OK, you have Parkinson's.
" Well, holy smoke! That was that was quite traumatic, I was in tears for sure.
It came as a complete shock to Paul and his family, and eventually forced him to give up his job.
Parkinson's is caused by an inability of the brain to release dopamine.
As well as affecting our mood, dopamine helps to regulate our movement.
With medication, Paul can get the dopamine he needs to keep his symptoms under control.
So I take Sinemet CR, control release, is the pink one.
And the two white ones are 2.
5mg each of Bromocriptine and as you see, I'm upright, I'm mobile, my shoulders are back.
A few years ago, Parkinson's researcher Professor Jon Stoessl decided to test this effective medication against a placebo.
We've always known that how people do when they have a serious condition has a lot to do with their attitude and that's intriguing to me.
Paul was recruited onto Jon's trial.
It would require him to stop taking his medication.
Without it, even walking can be difficult.
About a year and a half ago, I guess, I was about 50 feet from my house, I could literally see the front door.
I was sitting on the sidewalk, on the kerb, and I couldn't get home.
That wasthat was something else.
Took me about a half-hour to get homefrom a hundred feet.
Yeah.
Paul headed into hospital for the trial, without having had his medication, his Parkinson's symptoms in full flare-up.
And that's when they gave me this capsule.
And they gave you a half-hour, 45 minutes, you know, a normal period of time for the meds to kick in.
And boom, I was thinking, ah, this is pretty good.
My body becomes erect, my shoulders go back and I needed to go to the bathroom so I said, "I don't need any help, I'm fine.
" And I heel-struck my way down the hall and went to the bathroom.
But Paul hadn't been given any active medication.
He'd been given a placebo.
Well, I was shocked.
There's no way I could have done that.
I fully understand the effects of my medicine.
So how could a nothing create those same feelings? Yeah, I was really shocked.
Brain scans of patients with Parkinson's that were responding to the placebo helped to explain how Paul's symptoms had faded.
This slide shows three scans all taken from the same person with Parkinson's disease.
So, now you see the activity at baseline.
When they come in with no medication, their Parkinson's is not well controlled, there's a loss of dopamine in the brain, so we see lots of activity here.
With so little dopamine, someone with Parkinson's would be struggling to move and function.
Now we look at the middle slide and this is after the person is told that they're going to get active drug, but in fact they receive placebo.
And you can see a striking reduction in activity here which indicates that their brains have released a lot of dopamine.
The intense red colours in the striatum area of the brain show how little dopamine is present at baseline.
The decrease in the red colouring shows how the placebo can release dopamine just like the real drugs.
What we found is that, in somebody with Parkinson's disease, a placebo can release as much dopamine as amphetamine or speed can in somebody with a healthy dopamine system.
So it's a very dramatic response.
There are physical things that change in me when I take my meds and I didn't think a placebo would be capable of, you know There's no way - you know, how could a sugar pill or whatever, you know, make me feel like I had taken my Sinemet? I'm thrilled to death to know that I still have the ability on a short-term basis to produce dopamine and get going, right? Several studies have now shown that a placebo can ease the symptoms of Parkinson's - even if only in the short term.
Once again, the placebo works by tapping into the brain's internal pharmacy.
All these studies raise another intriguing question.
For a placebo to work, why do we need to believe that it's real? Pull your body into the rock, that's nice.
For Tor Wager, it's all about our expectations.
They can make a difference to what happens in our bodies - and that's true whether you take a pill, undergo an operation or climb a mountain.
Stand up on that back foot, Tor.
Climbing is a dangerous sport.
One false move, and things could go badly wrong for Tor - except, of course, that he's got a rope.
And that changes everything.
Going right.
Watch me here.
Good.
He expects to be safe.
Step through, beautiful, that's it.
And yet, without his belief that everything will be OK, he'd be so nervous he could barely climb.
When I was up there on the rock, my heart started beating, blood flow changed to my fingers, my brain's releasing opioids, releasing dopamine, and all those things are helping me perform, and they're also having various impacts on my body.
Those impacts depend on the feeling, the knowledge that I'm safe.
Take off that rope, it would be a completely different world - my heart rate would go crazy, I'd be sweating, and so forth.
Ultimately, it's about the link between our minds and our bodies.
Whether it's fear or hope, our thoughts and expectations can trigger chemical reactions that change our bodies.
So, if we expect a placebo to do something, it can release chemicals in our brains and change our physiology.
Scientists are now exploring just how much our expectations are capable of.
As well as pain, they've found that placebos can alleviate conditions from depression to insomnia, nausea to attention-deficit disorder.
And because it's all about your expectations, even the size and shape of a pill can make a difference to how well it works.
Studies have shown that capsules are more effective than tablets.
A large capsule is better than a small capsule.
Expensive medications are more effective than cheap medications.
Colour makes a difference - red pills are more effective for treating pain, blue pills are more effective for treating anxiety.
Unless you happen to be male and Italian, in which case blue is the colour of your national football team, and a symbol of immense excitement, passion, and heartache.
In that case, according to research, a blue pill won't help relax you - it will do the opposite.
But there are clear limits to what placebos can do.
They certainly won't fix a broken leg or help to shrink a tumour.
But in the areas where they seem effective, scientists are beginning to wonder how we can make the most of them.
There is, however, a problem with dummy pills and sham surgeries.
They rely on deception.
You're not told the truth.
That seems to be why they work - because you think they're real.
Obviously doctors don't want to lie to their patients.
So how do we harness the power of the placebo effect without lying? It's a question that one of the most prestigious medical schools in the world is hoping to answer.
In 2010, Harvard established a Program in Placebo Studies.
It aims to work out how we can use the placebo effect to make people better.
Ted Kaptchuk is the Director.
In the last 15-20 years, there's been an explosion of research in placebo studies.
We've learnt so much, but there's so much more to do.
The underlying goal is how do we learn to harness it and use it to help people get better, healthier and stronger lives? Recently, Ted decided to challenge one of the most basic assumptions about placebos.
He decided to conduct an experiment to see whether we really need to be duped for a placebo to work.
The conventional wisdom was that you have to use either deception or concealment in order for a placebo to work.
We decided to test whether or not you could still get a placebo effect if you gave a person a placebo and told them it was a placebo.
Linda Buonanno has suffered from irritable bowel syndrome for 16 years.
At times, the symptoms are bad enough that she doesn't want to leave home.
Along with 80 other sufferers of IBS, she was recruited onto Ted's trial.
She was given some pills and told they were a placebo, with no active ingredient, but that they might work, thanks to her own self-healing processes.
I said, "What? A placebo?" Because I'd just finished college as a medical assistant and I'm thinking, "He wants me to take sugar pills? "This isn't going to work.
" But I said I'd do it, so I went home, I started taking 'em .
.
and after three days I realised I wasn't in any pain any more.
I didn't have any intestinal pain, I didn't keep running to the bathroom or anything like that.
I didn't have any stomach cramps, I had nothing, all the symptoms, the severe symptoms I had, were gone.
I thought, no, this is not happening, this can't be, a sugar pill does not get rid of the problems, right? Linda wasn't the only study participant who reported improved symptoms from a pill she knew to be inactive.
I was taken aback when we finished the trial and our statisticians showed us the results and it was much stronger than we expected.
62 per cent said they got adequate relief from being on the placebo pill.
People who got nothing, I think it was around 30%, said they had adequate relief, so there's a real big difference, it was easy to detect.
But the study - and the supply of placebo pills - only lasted a few weeks.
When the pills ran out, Linda's problems returned.
It was three weeks, I think it was, and everything was fine, and then all of a sudden I'm not taking 'em any more and all the symptoms came back.
It was horrible, it was like, oh, man, I've got to suffer with this again? Linda decided to try and buy some more placebo pills.
I tried to go to one of the health food stores to buy the placebo pills but they didn't have them.
The fella in the store was, you know, thought it was kind of odd why I would be asking for placebo pills.
They had nothing else that would replace it, so I couldn't do anything, I was really disappointed.
Well, several patients actually asked us for more placebo pills.
Our Ethics Committee only gave us permission for three weeks of treating people with placebo pills, and, as you can imagine, I don't believe they're listed as a labelled drug in the United States.
So we weren't able to prescribe after that.
It's hard to know why Linda's symptoms disappeared, when she took something that she knew was chemically worthless.
The study only looked at whether it would work, not why.
But Ted has a theory.
What I think happened is that just seeing our study physician .
.
taking pills two times a day, in some way your body feels, recognises, moves in a way that's moving towards health.
This is the body knowing something that's beyond their ability to consciously be aware of.
I don't understand it, I don't know why and probably never will.
But there's something.
I think I'm wishing for a cure and I'm wishing for something to make this all disappear.
I think if I wish hard enough, it'll work, I guess.
Exactly why the pills worked remains a mystery.
And a small, short-term study like this certainly doesn't mean that we can simply replace real drugs with placebos.
But it does call into question the fundamental assumption about placebos - the idea that we need to be duped for them to work.
At Harvard, other scientists are searching for ways that we can use the power of the placebo without deception.
One of Ted's colleagues has studied something you might have thought wouldn't have anything to do with placebos.
And that is hypnosis.
There's a lot of overlap between the idea of placebo and the idea of hypnosis.
Separate the two index fingers.
And lift your hands and your arms up.
First of all, they're all based on belief, expectation and suggestion.
A hypnotic induction is a procedure that has no active ingredient except for the person's belief and understanding about what it is supposed to do.
Mike Gow is a dentist and a hypnotist.
He's preparing David for a major procedure.
He's going to extract his wisdom tooth.
So, as you can see from his X-ray, a lower wisdom tooth never developed in the first place and that's why the upper tooth is actually erupting down into the space where that tooth would've been.
When that happens, the tooth starts rubbing into the cheek, it starts biting down on the gum below, it also becomes very difficult for David to clean, and actually he's got some decay in this tooth, so almost impossible to get in to do a standard filling or restoration, and the tooth is in danger of breaking down and decaying further.
Normally, removing a wisdom tooth would require the injection of a strong local anaesthetic.
But David doesn't want one.
I don't like getting the injections and having the numb mouth afterwards.
So I had the opportunity to have hypnosis as a treatment for getting the wisdom tooth removed and I thought I'd give it a go.
David is having no pharmacological anaesthetic today.
He's not taking anything, he's not having any injections, this is going to be just hypnosis.
This is the plan, of course.
If we need to use anaesthetic, then we have it.
The only active ingredient in David's pain relief will be the way Mike interacts with him - his hypnotic induction.
Just notice this wave of relaxation now, more and more in control of your thoughts and feelings, calmer and calmer.
And if I lift the left hand all the way up The act of inducing hypnosis is a way of giving the person permission, disinhibiting them, so that they can now believe in their own abilities to block pain, to experience things differently.
Just notice how the index finger and thumb just feel kind of dull and insensitive, don't they? Yeah? Are you happy now to transfer that feeling around the tooth? Cold dull, and insensitive.
David's wisdom tooth is firmly encased in the bone that surrounds it.
Mike's first job is to gradually enlarge the socket.
DISTORTED: And just notice now, as you allow the mouth to open, just feeling that pressure.
Relaxed .
.
and comfortable.
Throughout the procedure, David has been told to rate his pain on a zero to ten scale.
And just write down a wee number now.
A zero, that's excellent.
As you allow the mouth to open again, just pushing and pressure, comfortablesensations.
Again, just write down any little number.
A one.
Clearly, David's pain scores aren't low because of any painkilling drugs he's received.
It's his own internal painkilling systems that are working - the same as those that can be activated by a placebo.
You might think of hypnosis as a procedure that allows people to turn on their own ability to produce a placebo effect.
Having widened the socket sufficiently, Mike is ready for the critical moment - tearing the tooth from the ligament that holds it in place.
Calm control.
Eyes open.
Wide awake.
That was awesome.
Very well done.
Good.
So, the final moment of removing the tooth, there's a lot of pressure, and I'd be interested to know what number you were at.
It wasprobably a four-ish.
About a four.
In the final moment, yeah.
Without any form of pain relief, I would expect it to be an 8 or a 9, without anything at all, so I think a number 4 is excellent.
It's such a different sensation.
I didn't really feel anything, just the point at which it pulled out, it was quite a sudden thing, but it wasn't anything more than that, I would have thought.
By changing his expectations about what he would feel, Mike enabled David to release the painkillers in his brain.
He gave him a placebo effect, not with a dummy pill or a sham surgery, but with words.
Hypnosis may not be the only way to get a placebo effect without deception, but it's certainly an excellent way to do that and you can think of it as an extra strength, non-deceptive placebo.
It seems that something about the relationship between practitioner and patient lies at the heart of inducing a placebo effect without deception.
So, is it possible for doctors to give patients a placebo effect by changing nothing more than their relationship with their patient? Answering that question could help provide the key to unlock our body's potential to heal itself.
Ted Kaptchuk set up an experiment to find out.
People with irritable bowel syndrome were recruited to be treated with acupuncture.
They were divided into different groups.
In one group, the acupuncturist's interaction with their patient was strictly limited.
We did not allow the practitioner to have an interaction with the patient.
And that meant the patient came in, the practitioner said, "My name isI've read the charts, "I'm going to treat you with acupuncture.
"I've been asked by the research scientists not to interact, to not confuse the scientific question.
" Hi, Mr Casey, come on in.
In another group, the patients were treated in as caring and supportive a manner as possible.
We added a warm supportive relationship, which included delving deeply into a patient's life, how does this affect your life, what's your relationship to these symptoms, how does it affect your being able to have family, friends, work.
And tell me what kind of improvements you'd like to see, so I get a good sense of that.
Empathy, expressing how we understood how difficult this was.
Some way, we had to touch the patient.
Thoughtful silence - we tried to have the practitioner think for a moment and then ask to repeat a question and some statement of confidence, "I think this is going to work.
" I'm pretty sure these treatments will be very helpful for you, and I hope they push you along to the next level.
All Ted was interested in was the placebo effect of this interaction - so all active treatment was removed.
The patients would receive acupuncture with needles that couldn't even puncture their skin.
The needle is It looks like an acupuncture pin, it's impossible to tell the difference unless you have I can barely see any difference.
Watch it go in.
See it go in.
And what happened is that it went up the shaft of the needle, like a magic sword.
It's no surprise that a patient treated in a caring way might feel more looked after.
You feel it yet? I do.
OK.
But it's not bad, right? It's not bad.
But could it really make them better? After all, it's just about being nice.
But Ted's results show that the relationship between a doctor and their patient is significant.
With no doctor/patient relationship, 42% had adequate relief.
And on the full monty, the everything, with doctor/patient and the practitioner relationship and all the other arms we got 62% reporting adequate relief.
What it's telling us is that a practitioner interaction dramatically optimises the placebo effect.
Ted's study shows that a doctor can potentially create a placebo effect just by changing the way they behave and the things they say.
It's still early days for the research at Harvard, but it suggests that we can use the power of the placebo effect to help make drugs and surgery more effective.
Placebo research is still in its infancy.
There's much more to learn.
Why do some people respond better than others? Do genetics play a role? What exactly does a doctor need to do to harness the placebo effect? But one thing we know for sure is that it's real.
Even the most sceptical people now accept that there is something in the placebo effect.
And that's a sea-change on 20 or 30 years ago where people were routinely describing the placebo as an experimental artefact.
The placebo effect is real, quantifiable and in fact you're doing quite well with an active therapy if you can get as good a response as the placebo response.
The pills and procedures of modern medicine have brought us unprecedented good health.
But in many cases it seems they're not acting alone.
The placebo effect is intertwined with everything we do in healthcare.
It was there from the beginning, it'll be there to the end.
The challenge facing researchers now is to better understand the mechanisms by which it works.
So that ultimately we can use it and make the most of the power of the placebo.
It comes in all shapes and sizes.
It can relieve pain, treat depression, and has even helped ease the symptoms of Parkinson's Disease.
And yet, it isn't a wonder drug.
In fact, there isn't anything in it.
As a scientist, it's unbelievable! These pills are placebos.
Dummy pills.
Sugar pills.
I'm thinking, "He wants me to take sugar pills? "This isn't going to work.
" But the latest research is starting to show why placebos do work.
And how you could make the most of them.
At the home of British cycling, at the Manchester velodrome, some of the country's top cyclists have gathered together.
They're elite.
Many are national champions, past or present.
They've been brought together by Dr Chris Beedie.
He wants to see if he can give them some pills to help them do something that would normally take months of training.
He wants to see if he can make them cycle faster than ever before.
We're going to get all the riders onto the track to do a sprint time trial, to get an idea from that of their baseline speed, and then four hours later we're going to give them a couple of these.
And we're expecting them to have an effect on their performance.
The cyclists have been invited to take part in an experiment looking at the effect of legal performance-enhancing supplements.
We're looking at testing a new ergogenic aid.
Half of you will be getting what we'd call a standard ergogenic aid, which is caffeine.
The other half will be getting caffeine, with some nitrate and some bicarbonate in those capsules.
And we're expecting that to do slightly better.
So to evaluate this we need two time trials from you, absolutely 100%, absolutely everything you've got in both time trials.
The cyclists' baseline performance is measured to get a sense of their natural competitive time.
And then - it's time for the pills.
OK, we've got the baseline performance, we now are going to give them some of these and see what effect these have.
One by one, the cyclists receive their performance-enhancing capsules from members of Chris' team.
Hi, Lisa, you've been randomised today to receive the caffeine.
Today you've been randomised to take the mixed supplement.
Hannah, today you've been randomised to receive the pure caffeine.
Today you've been randomised to receive the new supplement.
But nothing about today is quite as it seems.
Both sets of pills are exactly the same.
The cyclists are actually taking part in a very different experiment.
These are the capsules we're going to be using today.
We've got a couple of red ones and a couple of red and white ones.
They're fairly large and they look like they mean business.
They are, however, filled with cornflour.
Chris wants to see if the cornflour can improve the cyclists' times, even though they already do all they can to be as fast as possible.
But, having raced just a couple of hours ago, the riders are tired.
The thought of doing two in one day, it would never happen.
You'd normally sort of race one, and then a day or so, you'd start again Two in one day's going to be interesting! It's fair to expect that their second race of the day would be slower.
It's time to see what the pills can do.
Do you feel that the second ride felt easier? The first one, it got progressively harder during the ride.
The second ride, after about a lap and a half out of the four laps, it kind of got to a point where it was hurting but then it never got any worse.
The second ride felt better, yes.
I went half a second quicker, which is quite a lot over that distance.
I felt as if I was a little bit quicker second time round.
I felt really tired before I took it.
I think it may have started to kick in whilst I was warming up and I got a bit of a burst of energy and I felt ready to go again.
In spite of the fact that the riders were tired from their earlier race, analysis of today's times shows that more than half of them were quicker with the cornflour.
The placebo has even helped one cyclist to ride faster than ever before.
It was really good, really surprised to go quicker in the second run.
And a personal best as well by two tenths of a second, and to beat a couple of the lads that are here today that normally beat me, big surprise, yeah, really happy.
So, you did a PB, you felt the effects of the substance.
Yeah.
Um, the capsule we gave you was a placebo.
Oh, right, OK.
Really? SHE LAUGHS Really? Wow.
Today's trial is just a demonstration of what placebos can do.
But it's typical of what Dr Beedie has found in over a decade of experiments with hundreds of athletes.
Every study we've done we found a mean placebo effect.
In sports performance generally, we can see improvements quite frequently of two to three per cent.
Well, three per cent in many sports is probably the difference between first place in the Olympics and not being in the top ten.
So we're talking quite a substantial difference.
It's a little bit like your car's going a little bit faster but you're not using any more petrol.
Why that's happening, however, is still open to question.
It seems the pills that the cyclists took have the potential to make a real difference - and it's clearly nothing to do with the cornflour in them.
So how can a pill with nothing in it help someone to cycle faster than ever before? Since the advent of modern medicine, placebos have been treated with scepticism.
It's been assumed that they can do nothing.
They've been used only as dummy pills that new drugs have to beat to be considered effective.
But in recent years a number of studies have shown that there may be more to a placebo than we thought.
A few years ago, Dr David Kallmes decided to do a rather controversial experiment.
For 15 years, he's been fixing broken backs by injecting them with a special kind of surgical cement.
We saw terrific results from the procedure, really amazing results from the procedure.
But then Dr Kallmes noticed something that made him question how effective the procedure was.
I was aware of some rare cases where, believe it or not, the wrong vertebral body was treated, for whatever reason, and patients seemed to get some relief from that.
So there was some reason to suspect that there were numerous factors at play in the apparent effectiveness of the cement.
He decided to do something unusual.
He decided to put this established procedure to the test.
He designed a trial in which some patients would be given the real procedure and some would be given a placebo.
But in this case, the placebo couldn't be a dummy pill - it would have to be a fake operation.
There was scepticism from many people about whether this was worth doing.
I recall being at a meeting and I remember being screamed at and then later on being called a heretic for raising the spectre of the placebo effect in interventional procedures.
Nevertheless he went ahead with the trial.
All he needed was to recruit some patients.
A few years ago, Bonnie Anderson had an accident that led her to join the trial.
Well, when I slipped on the tiled floor in the kitchen here, I went complete feet went out from underneath me, I went flat on my back.
I could not move.
And I thought, oh, dear, I told Don, I said, "I'm afraid I broke my back.
" The pain was just very, very severe.
I couldn't stand up straight, I'd have to hold onto something.
She was in pain all the time, she could do very little.
I'd help him with the dishes, but he did all the vacuuming, he did more of the workload.
That part hasn't really changed that much! Oh, shut up! When Bonnie saw the doctor, a vertebral fracture was confirmed.
She was enrolled on the trial.
On a cold October morning, Bonnie arrived at the hospital, ready for her operation.
She couldn't know whether she was having a vertebroplasty or the pretend procedure - the placebo.
Dr Kallmes developed an elaborate ruse to ensure that patients wouldn't work out which group they were in.
The patient was brought into the room, was given medication by vein, was sterilely prepped and local anaesthesia was given.
And only after the anaesthesia was given onto the bone did we press the button to see whether the patient was randomised to the full vertebroplasty or to the placebo.
In both cases, no matter how they were randomised, we then opened the cement, which has a very strong odour like nail polish remover, to really simulate it for everybody in the room.
And if they were randomised to vertebroplasty, we then injected cement down into the bone.
If they were randomised to placebo .
.
we opened the cement, we had a script that we followed .
.
we pressed on the back and said, "OK, ma'am, the cement is going in now, everything's going fine, "things are going well, few more minutes here.
OK, we're all done.
" So we really simulated the procedure for the patient.
Bonnie felt better immediately.
The surgery did work very, very well for me.
It did so much for me.
I was really active.
The procedure transformed her life.
Within a week of the injection, I was able to play golf.
I took it a little easy, but I was able to play golf almost every day.
And I returned to some of my duties, as far as Well, I don't vacuum, but as far as dishes and stuff.
He won't say that, but it's true.
But Bonnie didn't have the real procedure.
She was in the placebo group.
And what made her so interesting was that she'd already had a real vertebroplasty once before.
Which meant she was uniquely able to compare the real thing with the placebo.
I thought they were both so successful that I could go ahead and do what I wanted to do without any problem.
And it wasn't just Bonnie that responded so well to the placebo.
When the results of the other 130 patients on the trial came in, they surprised everyone.
There was no statistically significant difference in degree of pain relief between the patients who underwent vertebroplasty and placebo, and more importantly there was no statistically significant difference in improvement in function between the patients who underwent vertebroplasty and placebo.
This study and another in Australia both suggest that a pretend procedure can be as effective as vertebroplasty - which has been carried out on over a million people.
Both the real thing and the placebo made patients better than if they'd received no treatment.
So how could a pretend procedure be so effective? Around the world, scientists are investigating how a placebo works.
They're trying to find out what's happening inside your body and brain when you experience a placebo effect.
It's a public holiday in the Italian Alps.
Tourists are heading up the mountain to spend a day skiing in the shadow of the Matterhorn.
But, for Fabrizio Benedetti, it's just another day in the office.
Instead of driving to the lab, instead of taking a bus or a train, we take a cable car.
On days like these When skies are blue The landscape is beautiful, it's a beautiful day.
But Fabrizio's laboratory isn't at the top of the mountain just for the sake of a pleasant commute.
He's using the low oxygen levels at high altitude to conduct an unusual experiment.
He's trying to find out whether a placebo effect is imagined, or whether somehow a placebo can cause real changes in our bodies.
OK, so here we are inside the station.
There are a couple of labs.
We have a living area, we have two bedrooms, the kitchen, the bathroom.
Italian-Swiss border is more or less here.
We work in Switzerland, we sleep in Italy.
For the past few years, Fabrizio has been bringing volunteers, like Marco, to his mountain-top laboratory to be studied.
He's conducting an experiment to see if anything happens to people when they expect extra oxygen, but don't actually get it.
So what we do is we give real oxygen or placebo oxygen - the tank of the oxygen is empty - and we compare the effect of real oxygen with placebo oxygen.
Fabrizio gives Marco a canister of what he's told is oxygen, and sets him off on a 30-minute hike.
Even mild exercise, that's pretty tiring and difficult.
That's the reason why we are here, of course.
Fabrizio wants to know as much as possible about what's going on inside Marco's body and brain.
His heart rate, brain activity, and even the neurotransmitters in his system, are all being monitored.
At this altitude, extra oxygen would be a great help.
If there is extra oxygen, of course, the muscles get more oxygen so their performance improves.
As they hike further, Marco is easily able to outpace Fabrizio's team of scientists.
You can see I cannot see him any more, actually.
But, of course, Marco doesn't have any extra oxygen.
So, has the fake oxygen just given him some kind of psychological boost? Or has it changed something in his body? By analysing the data he's gathered from Marco and the other subjects he's studied, Fabrizio has the answer.
It's all to do with the level of a neurotransmitter called PGE2.
When we come to high altitude, the low oxygen levels cause our blood oxygen levels to fall.
This makes our PGE2 levels go up.
And that leads us to feel some of the familiar symptoms of altitude sickness, like pain.
But extra oxygen can ease the problems.
When we give oxygen, there is a dramatic decrease in PGE2.
This is the typical response after oxygen administration with real oxygen.
The lower PGE2 level that comes from giving oxygen helps us to feel less pain, and therefore work harder.
But if you give someone fake oxygen you wouldn't expect the PGE2 levels to change.
In this case we give fake oxygen, which means placebo oxygen, and there's no change in blood oxygen saturation, you see - we have 84% of blood oxygen saturation - but there's a decrease in PGE2 anyway.
This means that this decrease is not due to oxygen in the body, but is due to expectation, to a placebo effect.
The fake oxygen is causing real physiological changes in Fabrizio's subjects - decreasing their levels of PGE2, causing them to feel less pain, and allowing them to work harder.
It's not imagination, it's not pure psychological effect, it's a real neurobiological effect.
Somehow, fake oxygen is producing real chemical changes in people's bodies.
It shows us just how real and measurable the placebo effect can be.
What it doesn't tell us is how that's happening.
Boulder, Coloradoin the foothills of the Rocky Mountains.
Tor Wager is trying to figure out how a placebo can change the chemicals in our bodies.
He's getting ready for another day inflicting mild torture on someone.
We do the thermal pain test a lot because it's not damaging and it's safe, but it is painful.
Right, Jake, come on in, you can have a seat right here.
Tor is hoping to fool Jake into believing that a standard moisturiser is a powerful pain relief cream.
He begins by applying some moisturiser to Jake's arm, and tells him what it is.
This is just to have something on your skin.
It won't provide any pain relief, and will serve as a control.
OK.
On a different spot, he applies some lidocaine - a local anaesthetic - which will dampen the pain that Jake feels.
We already know that it blocks pain, but we're just going to look and see whether it changes pain in your brain.
OK.
And finally, there's more moisturiser.
But Jake is told that it's also a local anaesthetic.
We'll do the analgesic on both of these spots.
We'll just wait just a minute for that to take effect.
Jake will then be subjected to heat pain on the different sites and be asked to rate them.
Meanwhile his brain will be scanned, allowing Tor to learn more about how a placebo works.
So we're going to give you a series of your level 8 temperatures, Jake.
And just use the trackball there, and just rate what you feel, moment by moment, track your pain continuously.
OK, so we're ready to go in.
This is the pain rating scale, he's rating his pain continuously, and the anchors here are no sensation to strongest imaginable sensation.
Jake's first heat treatment is on the control area.
All right, Jake, we've got it tuned and ready to go for the first task here, OK? With no anaesthetic, it's not a pleasant experience.
It's going up and it's just above very strong.
Oh, that's big, that's good! That was the control, this is with the lidocaine, just rate what you feel, we'll be scanning.
On the lidocaine site, the pain is noticeably reduced.
So with the control cream, they were between very strong and strongest imaginable, so they were pretty high.
And with the actual lidocaine cream they were between strong and very strong, so there was a substantial drop.
But how will Jake fare when the same heat is applied on the moisturiser that Tor has said is lidocaine? Last one, lidocaine number 2.
When he felt this temperature on the control area, he rated his pain above very strong.
Let's see what happens.
Oh, this one is the lowest so far actually, so that trial is lower than any of his lidocaine trials actually.
The basic conclusion is that here the placebo response for him is about as large as the lidocaine responses.
OK, Jake so how did that feel, by the way? Feels less painful.
Feels less painful? Yeah.
So I told you before that we were applying the real lidocaine on all four sites, right? But actually we didn't apply the lidocaine on all the sites.
So what we actually did is we applied the control here, so this is where your pain ratings were highest.
These two were both the real lidocaine, and these two were the placebo.
Interesting.
So, knowing that, do you feel like it worked? Or do you feel like, um The lidocaine or the placebo? The placebo.
Definitely, yes! The significance of Tor's work is that by scanning the brains of people as they experience a placebo effect, he's revealed clues about how a placebo works.
So when we've given people a placebo treatment, what we see is the release of endogenous opioids, which is the brain's own morphine, in a number of brain areas including this area here which is the periaqueductal grey, which is really a critical site for opioid-mediated pain control.
What that means is that the placebo effect is tapping into some of the same pain control circuitry as opiate drugs, like morphine.
What Tor has shown goes to the heart of the mechanism of how a placebo works.
A dummy pill or cream or surgery can release the naturally-occurring painkillers in our brains.
And it isn't just painkillers that a placebo can activate.
Our brains are capable of producing countless chemicals that we need - to stop pain or to feel it, to energise us or to help us sleep.
And a placebo can mimic many of them - from aspirin to alcohol.
The placebo effect taps into our natural pharmacy.
Drugs work because we have receptors for the drugs, and that means that there's some endogenous chemicals that our brains are producing that act on those receptors - the receptors evolved to respond to those natural chemicals.
So, a placebo can produce real results by tapping into the chemical systems that our bodies have evolved.
Just like modern medicines, a placebo effect relies on chemicals - the chemicals in our brains.
Scientists want to know just how much a simple sugar pill can do.
Can it only affect conditions which rely on self-reporting - like pain - or could it do much more? Paul Pattison lives on the outskirts of Vancouver.
It gives him easy access to the woods and mountains on the edge of the city.
But 12 years ago life took a turn for the worse, when he started to develop some unsettling symptoms.
I started to notice I was not my stride wasn't right, and I-I-Imy doctor referred me to a podiatrist, thinking something was wrong with my ankle, my foot, whatever.
So the podiatrist had me in there a couple of weeks later and he goes, "Oh, my gosh, you don't need a podiatrist, you need a neurologist.
" So I went back to my GP, got referred to a neurologist and he took one look at me and said, "OK, you have Parkinson's.
" Well, holy smoke! That was that was quite traumatic, I was in tears for sure.
It came as a complete shock to Paul and his family, and eventually forced him to give up his job.
Parkinson's is caused by an inability of the brain to release dopamine.
As well as affecting our mood, dopamine helps to regulate our movement.
With medication, Paul can get the dopamine he needs to keep his symptoms under control.
So I take Sinemet CR, control release, is the pink one.
And the two white ones are 2.
5mg each of Bromocriptine and as you see, I'm upright, I'm mobile, my shoulders are back.
A few years ago, Parkinson's researcher Professor Jon Stoessl decided to test this effective medication against a placebo.
We've always known that how people do when they have a serious condition has a lot to do with their attitude and that's intriguing to me.
Paul was recruited onto Jon's trial.
It would require him to stop taking his medication.
Without it, even walking can be difficult.
About a year and a half ago, I guess, I was about 50 feet from my house, I could literally see the front door.
I was sitting on the sidewalk, on the kerb, and I couldn't get home.
That wasthat was something else.
Took me about a half-hour to get homefrom a hundred feet.
Yeah.
Paul headed into hospital for the trial, without having had his medication, his Parkinson's symptoms in full flare-up.
And that's when they gave me this capsule.
And they gave you a half-hour, 45 minutes, you know, a normal period of time for the meds to kick in.
And boom, I was thinking, ah, this is pretty good.
My body becomes erect, my shoulders go back and I needed to go to the bathroom so I said, "I don't need any help, I'm fine.
" And I heel-struck my way down the hall and went to the bathroom.
But Paul hadn't been given any active medication.
He'd been given a placebo.
Well, I was shocked.
There's no way I could have done that.
I fully understand the effects of my medicine.
So how could a nothing create those same feelings? Yeah, I was really shocked.
Brain scans of patients with Parkinson's that were responding to the placebo helped to explain how Paul's symptoms had faded.
This slide shows three scans all taken from the same person with Parkinson's disease.
So, now you see the activity at baseline.
When they come in with no medication, their Parkinson's is not well controlled, there's a loss of dopamine in the brain, so we see lots of activity here.
With so little dopamine, someone with Parkinson's would be struggling to move and function.
Now we look at the middle slide and this is after the person is told that they're going to get active drug, but in fact they receive placebo.
And you can see a striking reduction in activity here which indicates that their brains have released a lot of dopamine.
The intense red colours in the striatum area of the brain show how little dopamine is present at baseline.
The decrease in the red colouring shows how the placebo can release dopamine just like the real drugs.
What we found is that, in somebody with Parkinson's disease, a placebo can release as much dopamine as amphetamine or speed can in somebody with a healthy dopamine system.
So it's a very dramatic response.
There are physical things that change in me when I take my meds and I didn't think a placebo would be capable of, you know There's no way - you know, how could a sugar pill or whatever, you know, make me feel like I had taken my Sinemet? I'm thrilled to death to know that I still have the ability on a short-term basis to produce dopamine and get going, right? Several studies have now shown that a placebo can ease the symptoms of Parkinson's - even if only in the short term.
Once again, the placebo works by tapping into the brain's internal pharmacy.
All these studies raise another intriguing question.
For a placebo to work, why do we need to believe that it's real? Pull your body into the rock, that's nice.
For Tor Wager, it's all about our expectations.
They can make a difference to what happens in our bodies - and that's true whether you take a pill, undergo an operation or climb a mountain.
Stand up on that back foot, Tor.
Climbing is a dangerous sport.
One false move, and things could go badly wrong for Tor - except, of course, that he's got a rope.
And that changes everything.
Going right.
Watch me here.
Good.
He expects to be safe.
Step through, beautiful, that's it.
And yet, without his belief that everything will be OK, he'd be so nervous he could barely climb.
When I was up there on the rock, my heart started beating, blood flow changed to my fingers, my brain's releasing opioids, releasing dopamine, and all those things are helping me perform, and they're also having various impacts on my body.
Those impacts depend on the feeling, the knowledge that I'm safe.
Take off that rope, it would be a completely different world - my heart rate would go crazy, I'd be sweating, and so forth.
Ultimately, it's about the link between our minds and our bodies.
Whether it's fear or hope, our thoughts and expectations can trigger chemical reactions that change our bodies.
So, if we expect a placebo to do something, it can release chemicals in our brains and change our physiology.
Scientists are now exploring just how much our expectations are capable of.
As well as pain, they've found that placebos can alleviate conditions from depression to insomnia, nausea to attention-deficit disorder.
And because it's all about your expectations, even the size and shape of a pill can make a difference to how well it works.
Studies have shown that capsules are more effective than tablets.
A large capsule is better than a small capsule.
Expensive medications are more effective than cheap medications.
Colour makes a difference - red pills are more effective for treating pain, blue pills are more effective for treating anxiety.
Unless you happen to be male and Italian, in which case blue is the colour of your national football team, and a symbol of immense excitement, passion, and heartache.
In that case, according to research, a blue pill won't help relax you - it will do the opposite.
But there are clear limits to what placebos can do.
They certainly won't fix a broken leg or help to shrink a tumour.
But in the areas where they seem effective, scientists are beginning to wonder how we can make the most of them.
There is, however, a problem with dummy pills and sham surgeries.
They rely on deception.
You're not told the truth.
That seems to be why they work - because you think they're real.
Obviously doctors don't want to lie to their patients.
So how do we harness the power of the placebo effect without lying? It's a question that one of the most prestigious medical schools in the world is hoping to answer.
In 2010, Harvard established a Program in Placebo Studies.
It aims to work out how we can use the placebo effect to make people better.
Ted Kaptchuk is the Director.
In the last 15-20 years, there's been an explosion of research in placebo studies.
We've learnt so much, but there's so much more to do.
The underlying goal is how do we learn to harness it and use it to help people get better, healthier and stronger lives? Recently, Ted decided to challenge one of the most basic assumptions about placebos.
He decided to conduct an experiment to see whether we really need to be duped for a placebo to work.
The conventional wisdom was that you have to use either deception or concealment in order for a placebo to work.
We decided to test whether or not you could still get a placebo effect if you gave a person a placebo and told them it was a placebo.
Linda Buonanno has suffered from irritable bowel syndrome for 16 years.
At times, the symptoms are bad enough that she doesn't want to leave home.
Along with 80 other sufferers of IBS, she was recruited onto Ted's trial.
She was given some pills and told they were a placebo, with no active ingredient, but that they might work, thanks to her own self-healing processes.
I said, "What? A placebo?" Because I'd just finished college as a medical assistant and I'm thinking, "He wants me to take sugar pills? "This isn't going to work.
" But I said I'd do it, so I went home, I started taking 'em .
.
and after three days I realised I wasn't in any pain any more.
I didn't have any intestinal pain, I didn't keep running to the bathroom or anything like that.
I didn't have any stomach cramps, I had nothing, all the symptoms, the severe symptoms I had, were gone.
I thought, no, this is not happening, this can't be, a sugar pill does not get rid of the problems, right? Linda wasn't the only study participant who reported improved symptoms from a pill she knew to be inactive.
I was taken aback when we finished the trial and our statisticians showed us the results and it was much stronger than we expected.
62 per cent said they got adequate relief from being on the placebo pill.
People who got nothing, I think it was around 30%, said they had adequate relief, so there's a real big difference, it was easy to detect.
But the study - and the supply of placebo pills - only lasted a few weeks.
When the pills ran out, Linda's problems returned.
It was three weeks, I think it was, and everything was fine, and then all of a sudden I'm not taking 'em any more and all the symptoms came back.
It was horrible, it was like, oh, man, I've got to suffer with this again? Linda decided to try and buy some more placebo pills.
I tried to go to one of the health food stores to buy the placebo pills but they didn't have them.
The fella in the store was, you know, thought it was kind of odd why I would be asking for placebo pills.
They had nothing else that would replace it, so I couldn't do anything, I was really disappointed.
Well, several patients actually asked us for more placebo pills.
Our Ethics Committee only gave us permission for three weeks of treating people with placebo pills, and, as you can imagine, I don't believe they're listed as a labelled drug in the United States.
So we weren't able to prescribe after that.
It's hard to know why Linda's symptoms disappeared, when she took something that she knew was chemically worthless.
The study only looked at whether it would work, not why.
But Ted has a theory.
What I think happened is that just seeing our study physician .
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taking pills two times a day, in some way your body feels, recognises, moves in a way that's moving towards health.
This is the body knowing something that's beyond their ability to consciously be aware of.
I don't understand it, I don't know why and probably never will.
But there's something.
I think I'm wishing for a cure and I'm wishing for something to make this all disappear.
I think if I wish hard enough, it'll work, I guess.
Exactly why the pills worked remains a mystery.
And a small, short-term study like this certainly doesn't mean that we can simply replace real drugs with placebos.
But it does call into question the fundamental assumption about placebos - the idea that we need to be duped for them to work.
At Harvard, other scientists are searching for ways that we can use the power of the placebo without deception.
One of Ted's colleagues has studied something you might have thought wouldn't have anything to do with placebos.
And that is hypnosis.
There's a lot of overlap between the idea of placebo and the idea of hypnosis.
Separate the two index fingers.
And lift your hands and your arms up.
First of all, they're all based on belief, expectation and suggestion.
A hypnotic induction is a procedure that has no active ingredient except for the person's belief and understanding about what it is supposed to do.
Mike Gow is a dentist and a hypnotist.
He's preparing David for a major procedure.
He's going to extract his wisdom tooth.
So, as you can see from his X-ray, a lower wisdom tooth never developed in the first place and that's why the upper tooth is actually erupting down into the space where that tooth would've been.
When that happens, the tooth starts rubbing into the cheek, it starts biting down on the gum below, it also becomes very difficult for David to clean, and actually he's got some decay in this tooth, so almost impossible to get in to do a standard filling or restoration, and the tooth is in danger of breaking down and decaying further.
Normally, removing a wisdom tooth would require the injection of a strong local anaesthetic.
But David doesn't want one.
I don't like getting the injections and having the numb mouth afterwards.
So I had the opportunity to have hypnosis as a treatment for getting the wisdom tooth removed and I thought I'd give it a go.
David is having no pharmacological anaesthetic today.
He's not taking anything, he's not having any injections, this is going to be just hypnosis.
This is the plan, of course.
If we need to use anaesthetic, then we have it.
The only active ingredient in David's pain relief will be the way Mike interacts with him - his hypnotic induction.
Just notice this wave of relaxation now, more and more in control of your thoughts and feelings, calmer and calmer.
And if I lift the left hand all the way up The act of inducing hypnosis is a way of giving the person permission, disinhibiting them, so that they can now believe in their own abilities to block pain, to experience things differently.
Just notice how the index finger and thumb just feel kind of dull and insensitive, don't they? Yeah? Are you happy now to transfer that feeling around the tooth? Cold dull, and insensitive.
David's wisdom tooth is firmly encased in the bone that surrounds it.
Mike's first job is to gradually enlarge the socket.
DISTORTED: And just notice now, as you allow the mouth to open, just feeling that pressure.
Relaxed .
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and comfortable.
Throughout the procedure, David has been told to rate his pain on a zero to ten scale.
And just write down a wee number now.
A zero, that's excellent.
As you allow the mouth to open again, just pushing and pressure, comfortablesensations.
Again, just write down any little number.
A one.
Clearly, David's pain scores aren't low because of any painkilling drugs he's received.
It's his own internal painkilling systems that are working - the same as those that can be activated by a placebo.
You might think of hypnosis as a procedure that allows people to turn on their own ability to produce a placebo effect.
Having widened the socket sufficiently, Mike is ready for the critical moment - tearing the tooth from the ligament that holds it in place.
Calm control.
Eyes open.
Wide awake.
That was awesome.
Very well done.
Good.
So, the final moment of removing the tooth, there's a lot of pressure, and I'd be interested to know what number you were at.
It wasprobably a four-ish.
About a four.
In the final moment, yeah.
Without any form of pain relief, I would expect it to be an 8 or a 9, without anything at all, so I think a number 4 is excellent.
It's such a different sensation.
I didn't really feel anything, just the point at which it pulled out, it was quite a sudden thing, but it wasn't anything more than that, I would have thought.
By changing his expectations about what he would feel, Mike enabled David to release the painkillers in his brain.
He gave him a placebo effect, not with a dummy pill or a sham surgery, but with words.
Hypnosis may not be the only way to get a placebo effect without deception, but it's certainly an excellent way to do that and you can think of it as an extra strength, non-deceptive placebo.
It seems that something about the relationship between practitioner and patient lies at the heart of inducing a placebo effect without deception.
So, is it possible for doctors to give patients a placebo effect by changing nothing more than their relationship with their patient? Answering that question could help provide the key to unlock our body's potential to heal itself.
Ted Kaptchuk set up an experiment to find out.
People with irritable bowel syndrome were recruited to be treated with acupuncture.
They were divided into different groups.
In one group, the acupuncturist's interaction with their patient was strictly limited.
We did not allow the practitioner to have an interaction with the patient.
And that meant the patient came in, the practitioner said, "My name isI've read the charts, "I'm going to treat you with acupuncture.
"I've been asked by the research scientists not to interact, to not confuse the scientific question.
" Hi, Mr Casey, come on in.
In another group, the patients were treated in as caring and supportive a manner as possible.
We added a warm supportive relationship, which included delving deeply into a patient's life, how does this affect your life, what's your relationship to these symptoms, how does it affect your being able to have family, friends, work.
And tell me what kind of improvements you'd like to see, so I get a good sense of that.
Empathy, expressing how we understood how difficult this was.
Some way, we had to touch the patient.
Thoughtful silence - we tried to have the practitioner think for a moment and then ask to repeat a question and some statement of confidence, "I think this is going to work.
" I'm pretty sure these treatments will be very helpful for you, and I hope they push you along to the next level.
All Ted was interested in was the placebo effect of this interaction - so all active treatment was removed.
The patients would receive acupuncture with needles that couldn't even puncture their skin.
The needle is It looks like an acupuncture pin, it's impossible to tell the difference unless you have I can barely see any difference.
Watch it go in.
See it go in.
And what happened is that it went up the shaft of the needle, like a magic sword.
It's no surprise that a patient treated in a caring way might feel more looked after.
You feel it yet? I do.
OK.
But it's not bad, right? It's not bad.
But could it really make them better? After all, it's just about being nice.
But Ted's results show that the relationship between a doctor and their patient is significant.
With no doctor/patient relationship, 42% had adequate relief.
And on the full monty, the everything, with doctor/patient and the practitioner relationship and all the other arms we got 62% reporting adequate relief.
What it's telling us is that a practitioner interaction dramatically optimises the placebo effect.
Ted's study shows that a doctor can potentially create a placebo effect just by changing the way they behave and the things they say.
It's still early days for the research at Harvard, but it suggests that we can use the power of the placebo effect to help make drugs and surgery more effective.
Placebo research is still in its infancy.
There's much more to learn.
Why do some people respond better than others? Do genetics play a role? What exactly does a doctor need to do to harness the placebo effect? But one thing we know for sure is that it's real.
Even the most sceptical people now accept that there is something in the placebo effect.
And that's a sea-change on 20 or 30 years ago where people were routinely describing the placebo as an experimental artefact.
The placebo effect is real, quantifiable and in fact you're doing quite well with an active therapy if you can get as good a response as the placebo response.
The pills and procedures of modern medicine have brought us unprecedented good health.
But in many cases it seems they're not acting alone.
The placebo effect is intertwined with everything we do in healthcare.
It was there from the beginning, it'll be there to the end.
The challenge facing researchers now is to better understand the mechanisms by which it works.
So that ultimately we can use it and make the most of the power of the placebo.