Placebo Research

[Guest guest]

Placebos do something....now if Abbott or GSK could just figure out how

to increase the " Convincing Power " and sell it at

$30,000/patient/year....

M.

**

The Chronicle of Higher Education

http://chronicle.com/daily/2005/11/2005112103n.htm

Today's News

Monday, November 21, 2005

Placebos Could Play a Role in Treating Some Conditions, Scientists

Say

By LILA GUTERMAN

Washington

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 that 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 doctors want 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 sham

medicine.

Those studies show that placebos affect the brain in much the same way

that actual treatments do, researchers reported here last week 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, " said Tor D. Wager, an assistant professor of psychology

at Columbia University. " They are deeper physiologically than we

have previously appreciated. "

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

how 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, said Christian S. Stohler, dean of the school of

dentistry at the University of land 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 at 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 suggested 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

covertly.

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

PET.

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 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 areas.

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 land, 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, " said Dr. Stohler. " Our

brain is on drugs. It's on our own drugs. "

Relief for Parkinson's

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 the 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 that

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 placebo

effect.

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

University.

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

regions.

She 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 had not yet taken its full

effect.

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 said, 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.

Raising Expectations

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 said, perhaps should imagine themselves

getting well. " What is expectation? " she asked. " How do

you cultivate it? "

Those are questions that all of the scientists involved in this research

would like to answer. Patients with chronic pain, said 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 said, " The

question is, How do things like this, or meditation, or biofeedback,

work? We don't know. "

Dr. Stohler, of land, agrees. " Getting a person to boost their

own machinery to improve health -- that's something that medicine needs

to know, " he said.

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-payments or

deductibles.

Copyright © 2005 by The Chronicle of Higher Education