Placebo releases dopamine

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

R. de la Fuente-Fernández, T. J. Ruth, V. Sossi, M. Schulzer, D. B. Calne and A. J. Stoessl (Neurodegenerative Disorders Centre, TRIUMF, University of British Columbia, Vancouver). Science 293:1164–1166, 2001. Funders were not read.

What happened

The team used positron emission tomography (PET) with [11C]raclopride, a tracer that sticks to dopamine receptors. When the brain releases dopamine, the dopamine competes with the tracer, so less tracer binds. They gave Parkinson's patients a placebo and saw tracer binding fall in the striatum, the dopamine-receiving movement hub.

• Alzforum reports a binding fall of 17 to 21 percent across the nigrostriatum, greatest in the posterolateral putamen.
• Alzforum says that fall was no different from the one in patients given apomorphine, a dopamine-mimicking drug. (Whether the two effects were additive is not stated in the sources read, so the earlier claim that they were not is removed.)
• The abstract concludes that the placebo effect in Parkinson's is powerful and is mediated through activation of the damaged nigrostriatal dopamine system (landmark 1).

Why it moved us toward a cure

Disease-modifying trials rely on clinical scores that a patient's expectation can move through real dopamine release. This explains why placebo groups often improve, why open-label studies look good, and why surgical trials of cell grafts and gene therapy need a sham-controlled arm. It makes blinding and placebo groups non-negotiable. It also helps explain why open-label reports like the early foetal grafts (landmark 3) were hard to interpret before sham-controlled trials.

Outcome

Advanced. It is a standard reference in discussions of placebo response in Parkinson's. It does not show that placebo changes the course of the disease; the paper reports a release of dopamine, not a change in disease course.

Sources

• de la Fuente-Fernández et al., Science 2001;293:1164-1166, DOI 10.1126/science.1060937, PMID 11498597 (abstract read via Europe PMC)
• Alzforum, "Putting Parkinson's placebo effect on a chemical footing"
• Not yet verified: the number of patients and exact study design (full text not read; Alzforum does not give them); how long the release lasts; how much the finding changed trial design in practice.