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Painful Pessimism: Our Expectations Influence How Well Drugs Work

Although the power of positive thinking is clear, little is known about how negative mind-sets affect the success of therapies














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An upbeat attitude can do more than put a spring in your step; it can also improve medical outcomes. Although the power of positive thinking is clear, little is known about how negative mind-sets affect the success of therapies.

Now cognitive neuroscientist Irene Tracey of the Uni­versity of Oxford and her collaborators have found that both sunny and cynical beliefs determine how well drugs work. The team published its findings February 16 in Science Translational Medicine.

In the study, 22 healthy participants underwent a func­tional MRI scan while a device heated their right calf to an uncomfortable level for 10 minutes. As expected, regions in the brain associated with pain perception were active.

During the rest of the fMRI experiment, the volunteers continuously received a rapid-acting painkiller called remi­fentanil in their bloodstream as they sensed the same heat on their leg. But the researchers misled them about when they were getting the drug. At first, the volunteers did not know treatment had begun, so they did not think their pain would decrease. Ten minutes later they learned that the drug was being administered, so they believed their discomfort would begin to subside. After another 10 minutes, the researchers told them the infusion had stopped, so the volunteers assumed their leg would start to hurt more.

The subjects indicated that their pain was much less intense and unpleasant when they believed they were re­ceiving the painkiller than when they thought they were not, even though the infusion had been constant. In fact, when they expected their pain to increase because they thought the infusion had been halted, that dismal outlook obliterated any benefit of the painkiller—their pain was the same as it was in the first, drug-free trial. In addition, the brain’s pain network was more active when they were expecting the worst, mim­icking the brain activity during the initial heat application.

The effects of pessimism are probably more pronounced in patients with chronic medical conditions because they are more likely to have experienced years of frustration with ineffective medications, Tracey says. “Doctors should not underestimate the significant influence that patients’ nega­tive expectations can have,” she cautions—and patients should speak up if they suspect their low expectations are getting the better of them.


This article was originally published with the title Painful Pessimism.



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  1. 1. ScienceisNotOpinion 09:15 AM 8/1/11

    Isn't this known as the Placebo effect?

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  2. 2. emilyhasbooks 10:29 AM 8/1/11

    How did the author conclude the title for this article? "Our Expectations Influence How Well Drugs Work" is an awfully concrete statement for a study only involving 22 subjects. "Our Expectations May Influence How Well Drugs Work" would have been more appropriate and less misleading.

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  3. 3. lamorpa 10:36 AM 8/1/11

    The 'pain of pain' (worry about or anticipation of pain) is as significant as the pain itself. I've done a great deal of training with the Clear Light Society (.org) and have learned ways to work with it that have helped me a great deal at times.

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  4. 4. DaoudaW 01:05 PM 8/1/11

    The title is misleading; most drugs are taken to affect a cure, but the study was only on pain management. It has long been known that pain management is very complex and involves both physical and psychological factors. My wife has ovarian cancer so I've become very aware of how many people truly believe that a positive attitude is the key to a cure. T'ain't necessarily so! We have had drugs fail totally when we expected them to work and vice-versa. Please, please, please Scientific American don't feed the anti-science, anti-pharma sentiment.

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  5. 5. bucketofsquid 04:19 PM 8/3/11

    There are a variety of factors that may apply with this situation. Placebo affect as previously mentioned as well as conformity expectations. I also notice the small sample size (as previously mentioned) and the total absence of a control group. This study shows that expectations are worthy of having a real study done but isn't useful for anything more than that.

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  6. 6. apark6 03:57 PM 7/7/12

    What should be included in this topic, because it is essential for any patient or professional to know; that is SET AND SETTING.
    The drug is only the source of 50% of the high, the other half comes from "The Set"; your expectation of the high one wants to feel, then "the Setting"- is what it says, the place where you use the drugs affects the altered state in 2 ways; one can enhance the high by creating in the setting, a mood or feel that is "altered" This can range from going to see a move you have been dying to see and selecting a theater with IMAX or great sound. When the first "Lord of the Rings" movie was released, I selected the Ziegfeld in NYC, because they have the best sound system, and had installed really comfortable high back seats. I even brought my favorite candy and cheese rice cakes. I made it as much a "natural High" as I could. The second effect setting has is it creates a "conditioned tolerance" When using is done in the same place consistently, the high is paired with the setting. When a person gets high in another setting, the effects skyrocket. This because the setting modulated the high to consistently be the same because setting is unchangeable. In a large city in the Midwest, a study was done on several hundred heroin addicts who had a near fatal overdoses. In collecting the data, they found that 90% were in a different setting when they overdosed. The researchers weren't expecting this and so "conditioned tolerance"is part of the our science.
    Andrew Park LCSW

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