The placebo effect weirds everyone out. I think we can say that without much fear of contradiction. It seems like magic, the fact that just thinking that you’re getting some treatment of benefit can have actual benefits.

Magic, though, it is not. This new study in the journal Neurology (press release here) is, at first, one of the weirder placebo effects yet documented. But if you look closer, it provides a scientific way to think about what’s going on. What the authors did was a double-blinded study in Parkinson’s patients, testing a new injectable drug affecting dopamine receptors. The patients got two shots of the same drug, one in a formulation which they were told cost $100 per dose, and the other in a formulation that they were told cost $1500 per dose. Half the group would take them in one order, and half in the other, with the second shot to be given after the effects of the first had worn off, four hours later. The entire study group was told that the purpose of study was to prove equivalence between the two formulations, and that the two were, in fact, believed to be of similar efficacy.

What everyone got, though, was saline. There was no drug. Both placebo doses improved motor function, which was expected: the placebo effect has been documented (PDF) in Parkinson’s patients before. But when patients were told that the first dose was the expensive one, the effect was greater than when they were told that the first dose was the cheap one. The belief is that that placebo effect is so noticeable in Parkinson’s (and in pain relief and in depression) because the reward and expectation system in the brain has a large dopamine signaling component, which matches well with these conditions. And this study shows another way to maximize that in turn.

The placebo effect itself is surely driven by neurotransmitters and hormonal signaling, as is the flip-side nocebo effect. Reward and expectations versus stress and anxiety – these are emotional states, to be sure, but they work through physical mechanisms that can alleviate or exacerbate other conditions. Some of those are going to have a higher signal-to-noise than others, and the effects will vary in different people according to their own emotional makeup. That showed up in this study as well:



After the study, the participants were told about the true nature of the study. “Eight of the participants said they did have greater expectations of the “expensive” drug and were amazed at the extent of the difference brought about by their expectations,” Espay said. “Interestingly, the other four participants said they had no expectation of greater benefits of the more expensive drug, and they also showed little overall changes.”

People probably feel more effect from higher-priced homeopathic preparations, too, although they’re the same distilled water as all the rest of them. (Probably a good reason to turn around and raise the prices, or launch a more expensive line from the same production runs). If you tell people that they’re drinking expensive wine, they report that it tastes better than the cheap stuff, even though they both came from the same bottle. That link raises some interesting philosophical points – when you’re reporting a sensation like taste, there’s no way to distinguish between what’s “objectively” in the substance being tasted versus what being “added” by the mind. Some parts of medicine are closer to that than we like to think.