[Paleopsych] CHE: Duping the Brain Into Healing the Body
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Wed Dec 7 01:25:02 UTC 2005
Duping the Brain Into Healing the Body
The Chronicle of Higher Education, 5.12.2
[I read somewhere that placebos work on dogs, a surprising result, since
dogs are immune from the sort of verbal propaganda humans are subject to.
One way it could work is this: a dog is given a medicine that has actual
medicinal effects. But most medicines don't directly go to whatever part of
the body is causing the difficulty. Rather the medicine triggers off a chain
of brain and nerve events. If this has happened a good many times, the
grooves down the nerve chain (so to speak: I like something more
medically-correct) repeatedly the nerve chains deepen. After a while, a
smaller dose or even no dose could trigger off the chain and thus work on
the dog. I recall a Russian guy named Pavlov who did something like this.
[Another thing: I read in _Science_ years and years ago that a major anomaly
had been discovered, namely that the placebo effect tends to be proportional
to the medicinal effect of the actual medicine, whereas one would think the
two would be random with respect to each other. I failed to follow up on the
controversy. Can anyone cue me in?]
Researchers analyze the mysterious placebo effect
By LILA GUTERMAN
The placebo effect -- it's all in your head. When you swallow sugar
pills instead of powerful medicine and your symptoms disappear, it's
all thanks to the power of your mind.
How does the brain perform this parlor trick? In the past, scientists
suspected that any apparent health benefits from placebos had little
more basis in biology than did sleight of hand. In studies of new
drugs, patients might tell their doctors they feel better because they
think that is what their doctor wants to hear. Or perhaps they would
have recovered without any treatment, real or sham.
But researchers now know that the placebo effect is real and grounded
in the physiology of the brain. Using techniques to peer inside the
skull, they have begun to find regions of the brain that respond to
placebos, and they have even watched a single nerve cell react to a
Those studies show that placebos affect the brain in much the same way
that actual treatments do, researchers reported here in November at
the annual meeting of the Society for Neuroscience. In other words,
the power to treat several troublesome disorders may be wrapped up in
the three-pound spongy lump of tissue protected by the skull.
The research points to the power of positive thinking -- even at the
unconscious level. When the brain expects relief, it can manufacture
some on its own. "The things you can change with a positive outlook
are profound," says Tor D. Wager, an assistant professor of psychology
at Columbia University. "They are deeper physiologically than we have
None of the researchers who study the mechanism of the placebo effect
suggest that doctors should prescribe dummy pills instead of real
medicine. But they say that the study of the placebo effect could
change the way scientists perform clinical trials of new treatments
and could even alter how we understand and treat pain, Parkinson's
disease, and depression.
By studying placebos, says Christian S. Stohler, dean of the school of
dentistry at the University of Maryland at Baltimore, "you crack into
disease mechanisms that might be very important for improving the
lives of many pain patients."
Fooling the Patient
Researchers gained their first glimpse of the causes of the placebo
effect in the late 1970s, when scientists discovered that under
certain conditions they could cancel the effect. In a study of pain
relievers, a drug called naloxone prevented patients on placebo pills
from experiencing the usual benefit. Since naloxone blocks the action
of painkillers called opioids, researchers figured that placebos must
stimulate the brain to produce its own opioids.
In the 1990s, another set of experiments provided more evidence that
the placebo effect was a real physiological phenomenon. Fabrizio
Benedetti, a professor of neuroscience at the University of Turin, and
others studied the effect without using a placebo.
Dr. Benedetti judged that a placebo's effect comes from the patient's
psychosocial context: talking to a doctor, observing the treatment,
and expecting improved health. So he took away that context by giving
study participants real drugs, but on the sly.
Patients were told that they would receive an active drug, a placebo,
or nothing through intravenous needles, and consented to get any of
the different treatments without knowing when any treatment would be
supplied. The scientists compared the results when a doctor overtly
gave the patient the drug and when a computer supplied the drug
without the patient's knowledge. Bedside manner, it turned out, made a
difference: Patients required far more painkiller if they unknowingly
received the medicine from a computer.
When the doctor gives a drug in full view, Dr. Benedetti said at the
neuroscience conference, "there is an additive effect of the drug and
of the placebo, the psychosocial component."
He suggests that his experimental setup could be extended to become
part of the testing procedure for new drugs. Clinical trials could
then compare covert and overt administration, rather than comparing
the active drug to a placebo. That way, none of the volunteers would
go through the trouble of participating without receiving the real
experimental treatment, and researchers could still demonstrate that
the drug was effective by showing that it reduced symptoms when given
Peering at the Brain
With the recent advent of modern brain-scanning techniques, scientists
gained the ability to look directly at the regions of the brain
involved in the placebo effect. In 2002 researchers in Finland and
Sweden published in Science the first brain images of the effect,
using a technique called positron emission tomography, better known as
The researchers pressed a hot surface onto the hands of nine male
volunteers, and then a doctor gave them injections of either a
painkiller or a placebo. When the researchers performed PET scans on
the men, both the drug and the dummy induced high blood flow --
indicating increased brain activity -- in an area of the brain called
the rostral anterior cingulate cortex. That area plays a key role in
the painkilling effects of opioid drugs.
Then in 2004, also in Science, Mr. Wager reported using functional
magnetic resonance imaging, or fMRI, to show that a placebo that
relieved pain also decreased activity in the brain's pain-sensing
Different people felt varying amounts of pain relief from the placebo.
The amount of pain reduction a volunteer experienced went hand in hand
with the amount of change in activity in the brain.
"Part of the effect of a drug," Mr. Wager said at the conference, "is
it changes the way you think about drugs."
Jon-Kar Zubieta, an associate professor of psychiatry and radiology at
the University of Michigan at Ann Arbor, and several colleagues,
including Dr. Stohler of the University of Maryland, peered deeper
into the brain's workings by finding out where the brain produces
opioids in response to placebo treatment.
They used PET scans along with a stain that marks opioid activity in
the brain. When the researchers gave male volunteers a painful
injection of saline solution into their jaw muscles, the scans showed
an increase of opioids in the brain. Most of the regions where the
brain produced painkillers coincided with the ones that Mr. Wager
identified as important.
"Expectation releases substances, molecules, in your brain, that
ultimately change your experience," says Dr. Stohler. "Our brain is on
drugs. It's on our own drugs."
The placebo effect helps not only people in pain but also patients
with diseases. In fact, scientists got their most detailed look at the
placebo effect by studying how single neurons responded to sham drugs
given to Parkinson's patients.
Parkinson's disease is a motor disorder caused by loss of brain cells
that produce dopamine. Some patients experience temporary relief of
symptoms from a placebo, and a previous study showed that the relief
occurred because the brain produced dopamine in response.
Patients who have Parkinson's disease sometimes receive surgery to
implant electrodes deep within the brain. The electrodes can stimulate
a neuron or record its activity. Dr. Benedetti, of the University of
Turin, and his colleagues enrolled 11 patients who underwent surgery
for this type of treatment. They gave the patients a placebo
injection, telling them it was a powerful drug that should improve
their motor control. The researchers then compared the activity of a
single neuron before and after injection of the placebo.
In the six patients who responded to the placebo -- who demonstrated
less arm rigidity and said they felt better -- the rate of firing of
the neuron went down. (Nerve cells "fire," or generate electrical
impulses, in order to send signals to neighboring neurons.) The
neurons' firing rate did not change for people who experienced no
Another disorder that shows clinical improvement with placebos is
depression. Depressed patients' moods often lift when they take a
placebo, although the effect does not last, and they normally need to
seek real treatment, according to Helen S. Mayberg, a professor of
neurology and of psychiatry and behavioral sciences at Emory
Dr. Mayberg became immersed in placebo research a few years ago, when
she did a PET study of the brain's response to an antidepressant and
to a placebo.
In her study of 15 depressed men, four who had taken Prozac and four
who had received a placebo experienced a remission of their symptoms.
At the end of six weeks, after allowing the drug sufficient time to
take effect, Dr. Mayberg took PET scans. For patients whose symptoms
improved, the regions where the brain activity increased after a
patient took a placebo formed a subset of the regions that increased
after a patient took the true drug.
"Drug is placebo plus," she said at the conference.
In patients whose symptoms did not improve, whether they were on
Prozac or on the placebo, the brain activity did not increase in those
She had published the results of that study in 2002, but at the
conference she reported a new analysis of her data. In the study, she
had also collected brain scans one week after patients had begun
receiving their treatments, even though the drug hadn't yet taken its
Still, people whose symptoms later improved, whether they took the
placebo or Prozac, again had increased brain activity in similar
areas. One week into treatment, she says, the men's state of mind
could be interpreted as a "heightened state of expectation" since they
were anticipating clinical improvements. Nonresponders did not show
those patterns, so such expectation could be key to whether a
depressed patient will recover.
Dr. Mayberg would like to find ways to help those who do not respond
to antidepressant drugs, and she surmises that expectation could make
the difference. Such patients, she says, perhaps should imagine
themselves getting well. "What is expectation?" she asks. "How do you
Those are questions that all of the scientists involved in this
research would like to answer. Patients with chronic pain, says Dr.
Zubieta of Michigan, perhaps have lost the ability to produce the
brain's natural painkillers. "If you are able to recruit mechanisms
that help you cope with stress or pain, that's a good thing," he says,
"The question is, how do things like this, or meditation, or
biofeedback, work? We don't know."
Dr. Stohler of Maryland agrees: "Getting a person to boost their own
machinery to improve health -- that's something that medicine needs to
It may be especially urgent for patients with dementia, according to
Dr. Benedetti. At the conference, he reported preliminary results that
patients with Alzheimer's disease may not experience placebo effects
at all. He found that Alzheimer's patients felt no difference between
overt and hidden administration of painkillers. To Dr. Benedetti, that
suggests that the psychological components of treatments -- the
expectation of health improvements, and the circuits that such
expectations create in the brain -- are absent.
Perhaps, he said at the conference, doctors need to take that loss
into account when prescribing any drug for Alzheimer's patients. Those
patients may need higher doses of many drugs, such as painkillers, if
their brain has stopped aiding the drug's action.
The mind, it seems, may play a critical role in treating diseases. And
its services come free of charge, with no co-payment or deductible.
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