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Placebo Effect Probed in Parkinson's

Sham injections trigger release of dopamine, study says

THURSDAY, Aug. 9, 2001 (HealthDayNews) -- Scientists have long believed that Parkinson's disease patients seem to be highly susceptible to the placebo effect. Now they know more about why.

Sham treatment of people with Parkinson's triggers a flood of the same brain messenger molecule that "active" drugs target -- and from the same region of the brain that's damaged by the disorder, new research says.

"We conclude that dopamine release in the nigrostriatal system is linked to expectation of a reward -- in this case the anticipation of therapeutic benefit," write the authors, led by Raul de la Fuente-Fernandez, a visiting scientist at the University of British Columbia's Neurodegenerative Disorders Center.

The findings, which appear in the Aug. 10 issue of Science, also might explain how the placebo effect works in patients with other conditions since dopamine is intimately involved in the brain's reward mechanism.

"To our knowledge this is the first time that anyone has demonstrated a chemical or physiological basis for the placebo effect," says co-author Dr. Jon Stoessl, a neurologist at the University of British Columbia.

The legitimacy of the placebo effect was challenged earlier this year by Danish researchers who reported in the New England Journal of Medicine that the phenomenon is largely overstated. If it exists at all, they said its impact is minor and almost entirely limited to easing pain.

"Clearly, we disagree with their conclusions," says Stoessl, whose group is preparing a rebuttal to that study.

Stoessl and his colleagues studied the impact of a saltwater solution on the brains of six Parkinson's patients who also received the drug apomorphine, which stimulates dopamine receptors. Using positron emission tomography (PET) scanning, the researchers saw that the addition of the placebo sparked as much as a 19 percent increase in dopamine activity in the brain.

"The magnitude of the effect is quite substantial and much larger than most people would have anticipated," Stoessl says.

But other researchers reacted warily to the latest work.

"There is no question that the psychological setting of a person can temporarily influence" a Parkinson's patient's symptoms, says Dr. Abraham Lieberman, a neurologist at the University of Miami and medical director of the National Parkinson Foundation.

Lieberman says patients confined to wheelchairs have been known to jump to their feet in a fire, while tremors and other motor symptoms of the disease often change during periods of stress, a phenomenon called "kinesia paradoxica." Yet once the danger or stress has passed, the immobility returns. "The trouble is, we can't control it," he says.

Dr. Raj Pahwa, who directs the Parkinson's Disease Clinical and Research Center at the University of Kansas in Kansas City, says he has "a lot of concerns" about the latest study.

"They did in it just six patients, and they studied a very short-acting drug," says Pahwa. "The issue is for how long [the placebo effect lasts]. It's not whether they get a benefit or not. We have known forever that patients with Parkinson's definitely have placebo responses."

What's more, Pahwa says apomorphine comes as an injection, not a pill, which might increase its effect on patient psyche more than tablets.

However, Stoessl says the injection was "minuscule" and probably insufficient to signal a surge of dopamine.

What To Do

To find out more about Parkinson's disease, try the American Parkinson Disease Association or the National Parkinson Foundation.

For more on the placebo effect, check Creighton University. You can also try the Skeptic's Dictionary.

SOURCES: Interviews with Jon Stoessl, M.D., professor of neurology, director of the Neurodegenerative Disorders Center, University of British Columbia, Vancouver; Abraham Lieberman, M.D., professor of medicine, University of Miami Medical School, medical director of the National Parkinson Foundation, and Raj Pahwa, M.D., director, Parkinson's Disease Clinical and Research Center, University of Kansas, Kansas City; Aug. 10, 2001, Science
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