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Revealed: how the mind processes placebo effect

July 18, 2007 By Michael Hopkin This article courtesy of Nature News.

Expecting a big reward helps the reward to come true.

Neuroscientists have found that people who experience a strong dose of pleasure at the thought of an upcoming reward are more susceptible to the placebo effect.

The research shows how the placebo effect, in which patients perceive a benefit from a medical treatment despite it having no genuine therapeutic activity, hinges on the brain's 'reward centre' — a region that predicts our future expectations of positive experiences, and which is also implicated in gambling and drug addiction. Greater activity in this brain region, called the nucleus accumbens, is linked to a stronger placebo effect, the new research shows.

This kind of mechanistic understanding of how the brain reacts to placebo treatments could help doctors to boost the effect, argues Jon-Kar Zubieta of the University of Michigan, Ann Arbor, who led the research.

"This is driving the idea that you can manipulate the placebo effect, to increase it for therapeutic treatment," he says.

Conversely, reducing or eliminating variations in the placebo effect could improve the accuracy of medical trials, which evaluate the effects of new therapies against that of a placebo. Reducing the variation in placebo effects among different volunteers could help to standardize trial results.

Great expectations

Zubieta and his team evaluated the placebo effect by giving volunteers a painful injection of salt solution into the cheek. Subjects were then told that they would be randomly assigned an injection either of painkiller or of placebo. In fact, all volunteers received a placebo. Later, some of the same patients were retested and not offered a second injection at all.

This is driving the idea that you can manipulate the placebo effect, to increase it for therapeutic treatment.
Jon-Kar Zubieta, University of Michigan
Participants generally reported more reduction in pain when given the placebo injections than those not given any placebo treatment at all, Zubieta and his colleagues report in the journal Neuron1. But the volunteers showed significant variations in the strength of their placebo effects.

The researchers suspected that the effect may be linked to the brain's reward centre, which kicks into life when a reward (in this case, pain relief) is expected. They scanned the brains of 14 of their 30 volunteers to monitor the production in the nucleus accumbens of a brain signalling chemical called dopamine, which is boosted in response to reward anticipation.

Activity in the nucleus accumbens was greater in those patients experiencing a strong placebo effect, the researchers found. "If your dopamine system doesn't work very well your placebo effect is probably going to stink," Zubieta says.

What's more, people who tended to show a strong placebo effect also had higher reward expectation in general, as demonstrated by a game in which they were told that they would be given varying amounts of money. During the game, their brains were scanned to assess their levels of optimism that the reward would be a handsome one.

Brain booster

The findings raise the possibility that patients could be given medically active drugs to activate or boost the placebo effect, although Zubieta warns that we don't really know how to do this yet. Drugs already exist to boost the brain's dopamine system, but can have a bizarre range of side effects, including turning patients into reckless gamblers as their reward-expectation centre goes into overdrive, he points out.

A better way to approach the problem might be to encourage doctors to be upbeat when telling patients about their treatments, suggests Chris Frith, a neuropsychologist at University College London. That should boost the patients' anticipation of reward and cure. "The doctors who do best are the ones who are most deluded that their treatments do work," he says.

It is still unclear how any anticipation of reward might then specifically affect the physiological problem being suffered by a patient. It is possible that the reward-anticipation triggers the production of homemade painkillers called endogenous opioids, for example. If so, it may be possible for people to control the release of such chemicals through thought (and belief) alone. "Is it possible to release these at will?" Frith asks.


  1. Scott, D. J. et al. Neuron 55, 325-336 (2007).


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