Revealed: how the mind processes placebo effect

Expecting a big reward helps the reward to come true.

Michael Hopkin

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.

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.

La capacité d'auto-illusion ou la conviction de l'acteur seraient donc la clef d'un effet placebo maximal. Les cours de comédie seront bientôt au cursus universitaire médical. On pourrait aussi verser plus de crédits à la recherche médicale pour améliorer les traitements et les rendre largement supérieurs à ce que l'effet placebo peut produire.

Vitamin C Offers Little Protection Against Colds, Review Finds

Science Daily — Unless you run marathons, you probably won't get much protection from common colds by taking a daily supplemental dose of vitamin C, according to an updated review of 30 studies.

Conducted over several decades and including more than 11,000 people who took daily doses of at least 200 milligrams, the review also shows that vitamin C (ascorbic acid) does little to reduce the length or severity of a cold, according to the researchers at the Australian National University and the University of Helsinki.

However, they found that people exposed to periods of high stress -- such as marathon runners, skiers and soldiers on sub-arctic exercises -- were 50 percent less likely to catch a cold if they took a daily dose of vitamin C.

For most people, the benefit of the popular remedy is so slight when it comes to colds that it is not worth the effort or expense, the authors say. "It doesn't make sense to take vitamin C 365 days a year to lessen the chance of catching a cold," said co-author Harri Hemilä, a professor in the Department of Public Health at University of Helsinki in Finland.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Since the discovery of vitamin C in the 1930s, controversy regarding its efficacy in treating ailments from lung infections to colds has surrounded it. In the 1970s, Nobel Prize-winning chemist Linus Pauling popularized its regular use. His book, "Vitamin C and the Common Cold," encouraged people to take 1,000 milligrams of the vitamin daily.

The current recommended daily allowance of vitamin C is 60 milligrams. An eight-ounce glass of orange juice has about 97 milligrams of vitamin C.

Despite early mixed results and later evidence against its efficacy, charismatic Pauling became the world's vitamin C champion. "Pauling never recanted and never backed down," said Wallace Sampson, founding editor of the Scientific Review of Alternative Medicine and emeritus professor of medicine at Stanford University.

Regardless of the evidence against it, vitamin C remains popular because many people -- including those funding studies -- want to believe that it works, said Sampson, who debated Pauling on the radio and in letters.

These days, there is less interest in studying vitamin C and the common cold, said Hemilä, who has studied the vitamin for more than 25 years. The Cochrane Review was originally published in 1998 and updated in 2004 and this year. The latest update includes a single new study on the Vitamin C-cold connection.

However, researchers continue to examine vitamin C alone and in combination with other vitamins and substances, such as Echinacea, for its efficacy in preventing and treating diseases and conditions, including cancer. This is not necessarily a good thing, Sampson said. "It's broadside quackery."

Hemilä said he sees little use in further study for colds for adults. However, he would like to see more studies on vitamin C and colds in children and vitamin C and pneumonia. Vitamin C is not a panacea, but it is not useless either, Hemilä said. "Pauling was overly optimistic, but he wasn't completely wrong."

Note: This story has been adapted from a news release issued by Center for the Advancement of Health.

Le mythe de la vitamine C a la vie dure, malgré toutes les études scientifiques montrant que son efficacité est extrêmement limitée et s'applique à des cas peu courants comme celui des athlètes de haut niveau en effort intensif. Les crédules adeptes des pseudo-médecines continuent à en faire la publicité, pour le plus grand avantage financier des laboratoires pharmaceutiques qui la commercialisent.