09 Aug 2001

A study published in May in the New England Journal of Medicine questioned long-held views on the placebo effect, sparking intense debate (Hrobjartsson and Gotzsche). In the August 10 Science, scientists in Jon Stoessl's laboratory at the University of British Columbia, Vancouver, show that the placebo effect is not only demonstrable in Parkinson's disease (PD), but that it owes its existence to activation of the compromised dopaminergic pathway associated with this disorder.

Using positron emission tomography (PET) of the substantia nigra, they measured changes in amount of the dopamine competitor raclopride, which inversely correlate with the level of dopamine itself. The authors report two main findings.

First, patients receiving placebo had a drop in raclopride binding throughout the nigrostriatum, indicating increased dopamine production. The raclopride binding reduction was greatest in the posterolateral part of the putamen, averaged 17 to 21 percent depending on the region studied, and was no different from that observed in patients who received the dopamine agonist apomorphine. In addition, the estimated increase in dopamine was greater in the patients who received a placebo and perceived an effect.

Secondly, the effects of the placebo and apomorphine were not found to be synergistic. Patients who received a placebo and perceived an effect respond less well to apomorphine than did those who received placebo and did not perceive an effect, indicating that the placebo-stimulated activity of the dopaminergic pathway was not further increased by the drug.

"It's a fascinating study, says Daniel Tarsy, Harvard Medical School. "It provides a chemical basis for the PD placebo effect that has been observed for some time in the clinic."—Tom Fagan