[Paleopsych] CHE: Duping the Brain Into Healing the Body

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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

    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
    sham medicine.

    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
    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 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
    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

    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
    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 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.

    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 says, perhaps should imagine
    themselves getting well. "What is expectation?" she asks. "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, 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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