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.