Horizon (1964–…): Season 50, Episode 9 - The Power of the Placebo - full transcript
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, Colorado...in 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-I...my 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 was...that was something else.
Took me about a half-hour
to get home...from 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,
comfortable...sensations.
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 was...probably 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 is...I'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, Colorado...in 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-I...my 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 was...that was something else.
Took me about a half-hour
to get home...from 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,
comfortable...sensations.
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 was...probably 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 is...I'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.