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Great expectations: Research explains placebo effect


A spate of recent studies demonstrating the powerful effect of placebos, or fake treatments, reinforces the idea that what we think about our medical care really can affect our health.

The new research, particularly studies using the latest in brain scanning technology, is giving scientists the most detailed and direct evidence yet into how expectations - beliefs about whether a treatment will work - can have an actual, observable effect in patients' brains and on their well-being.

In one study, researchers hooked 14 healthy young men up to PET scanners that monitored changes in brain function. The researchers injected a pain-inducing solution into the men's jaw muscles and asked them to rate their pain every 15 seconds for 20 minutes.

Intermittently, they gave them intravenous injections of plain salt water, though the men were told these were painkillers.

Every time the men got the "painkillers," the PET scans showed their brains were pumping out natural, opiate-like painkillers called endorphins, said Dr. Jon-Kar Zubieta, the study leader and associate professor of psychiatry and radiology at the University of Michigan Medical School. This showed that even though the "painkillers" were fake, the men's beliefs caused changes in their brains and lessened their perception of pain.

But it takes a healthy brain to produce a placebo effect. In a soon-to-be released study, Italian researchers have shown that the expectation of pain relief does not lead to reduced pain in people with Alzheimer's disease.

Even in people with healthy brains, not all placebos are created equal. Last week, Harvard researchers announced results of a new study that showed that sham acupuncture provides more pain relief than a sugar pill that comes with a promise of relief. The conclusion, said researcher Ted Kaptchuk, is that medical ritual "may be a critical component" of treatment.

The placebo effect can work in reverse, too, through its evil twin, the "nocebo" effect. At least 25 percent of the time, when people take a placebo, they report side effects such as headache, insomnia and fatigue, said Dr. Arthur Barsky, a psychiatrist at Brigham and Women's Hospitals in Boston.

In other words, telling patients about potential side effects can make it more likely that they will occur.

Eventually scientists hope to determine more precisely what their drugs are doing and how the placebo effect contributes to healing, though it is still unclear how best to harness the placebo effect to make patients feel better.

"The whole point of all this [research] is, how do we capitalize on the placebo response?" said Dr. Helen Mayberg, a professor of psychiatry and neurology at Emory University School of Medicine in Atlanta.

The research shows that it's not possible to "psych yourself" into making a drug work. But not trusting your care - whether it's popping a pill handed to you by a doctor, or undergoing 30 minutes of treatment from an alternative medicine practitioner - is likely to undermine its benefits.

"This is not about the power of positive thinking, it's about positive expectations," Mayberg said. "I can't think myself well, but if you go in with a new treatment and say, 'This is not going to work,' it probably won't help you."

In general, 30 percent to 60 percent of patients with ailments ranging from arthritis to depression report an improvement in symptoms after receiving a placebo.

One-third of depressed people feel better after taking placebos, compared with 50 percent to 60 percent of those taking real antidepressants, said Dr. Andrew Leuchter, vice chairman of the department of psychiatry at the University of California, Los Angeles.

"The placebo effect is the summation of all the things we do in treatment that help people get better that are not part of a known specific treatment," he said. "I define it that broadly because when we interact with someone in a positive way, when we give them encouragement and support, and also when they become part of the health care system - no longer sitting at home ill, but in a milieu where they are getting treatment - we tap into positive expectations."

The effects of placebos wear off with time, but real drugs keep working. Because of this - and medical ethics - no one is suggesting that doctors prescribe their patients sugar pills or sham treatments. But combining real medicines with the "placebo effect" does more than either can alone.

"The take-home message is that when you get an active drug, you get the effect of the drug itself and the placebo effect," said Zubieta of the University of Michigan School of Medicine.

The newest research, much of it based on brain imaging techniques, provides direct evidence of how the placebo effect works. Among the most recent findings:

Columbia University researcher Tor Wager has used brain scans to map where in the brain the placebo response occurs. Some turned out to be areas activated when a person is in pain, including the thalamus, insula and anterior cingulate cortex.

Curiously, the placebo effect can even kick in when there's no placebo, according to Dr. Fabrizio Benedetti, a professor at the University of Turin in Italy who also conducted the Alzheimer's research.

In one study, Benedetti hooked pain patients to a computerized injection device. In some cases, the computer administered morphine without the patients knowing it and in others, a doctor gave the drug in full view. The hidden therapy was much less effective than the open one, showing that to get the most from a treatment, you have to know you are getting it.

Similarly, Parkinson's patients improved more when they were told doctors were activating a stimulator in their brains than when the stimulator was turned on without their knowledge.

Though all this makes for compelling research, it's still unclear what it means to patients and their doctors. "That's the new frontier," Harvard's Kaptchuk said.

What is clear is that having a reasonably positive belief that a new treatment will work can at least stack the odds in your favor. Not focusing on all the possible side effects makes sense, too. It's also essential to pick a doctor you trust so that the doctor's words of encouragement can boost the chance that a treatment will work for you.

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