Brain imaging reveals the substance of placebos. Expectation alone triggers the same neural circuits and chemicals as real drugs.

"Placebos are supposed to be nothing. They're sugar pills, shots of saline, fake creams; they're given to the comparison group in drug trials so doctors can see whether a new treatment is better than no treatment.

But placebos aren't nothing. Their ingredients may be bogus, but the elicited reactions are real. "The placebo effect is in some way the bane of the pharma industry's existence because people have this nasty habit of getting better even without a specific drug," says David Spiegel, a psychiatrist at Stanford University School of Medicine.

It all boils down to expectation. If you expect pain to diminish, the brain releases natural painkillers. If you expect pain to get worse, the brain shuts off the processes that provide pain relief. Somehow, anticipation trips the same neural wires as actual treatment does.

Scientists are using imaging techniques to probe brains on placebos and watch the placebo effect in real time. Such studies show, for example, that the pleasure chemical dopamine and the brain's natural painkillers, opioids, work oppositely depending on whether people expect pain to get better or worse. Other research shows that placebos can reduce anxiety.

The first brain imaging study to show what happens in the brain during the placebo effect was not necessarily aiming to do so. Its goal was to use brain scans to study what happens when people take apomorphine, which is a drug for Parkinson's disease, a condition marked by a lack of dopamine. The drug brings quick relief but is infamous for its unpleasant side effects of dizziness and nausea. Led by neurologist Raúl de la Fuente-Fernández of the University of British Columbia in Vancouver, the project used PET scans to monitor the activity of the brains of Parkinson's patients the same day patients took the drug. PET scans are tools to identify where the brain is activated and which brain chemicals are involved in a task.

But patients in the study experienced so many side effects from the drug that the researchers had to cancel the PET scans. De la Fuente-Fernández wondered whether the combination of undergoing PET scans and worry over side effects made some patients react to the drug more strongly than they should have. So he changed the protocol. On scanning days, investigators gave the drug in several injections rather than a single dose. Participants knew that one dose was placebo, but not which one.

That simple adjustment reduced side effects, kept the trial going and led to a Science paper in 2001 showing that placebos trigger dopamine release through the same circuitry as Parkinson's drugs. This finding was "serendipity, just serendipity," says de la Fuente-Fernández."

... . Science News