Nocebo: Placebo Effect Works in Reverse

A new study suggests that the placebo effect may work in reverse.

In the past, placebos have been given to participants in studies to detect whether the participant would still feel the effects of the “drug” they thought they were being given. This has proved to be true, and so the opposite may be true as well now.

In the study, the participants were given a dose of a potent painkiller, remifentanil, and their pain levels fluctuated greatly depending on their belief of whether they were receiving the pain killer or not….when in reality, the dosage did not change for the full length of the study.

"We found that positive treatment expectancy substantially enhanced—doubled–the analgesic benefit of remifentanil. In contrast, negative treatment expectancy completely abolished remifentanil's painkilling effect," said lead researcher Dr. Ulrike Bingel, of the department of neurology at the University of Hamburg Medical Center in Germany. Researchers from Oxford University in the U.K. also assisted with the study.

"Intriguingly, this very same pattern was found in the activation of those brain areas that are well known to be involved in the intensity of pain," Bingel added.

Bingel's team supplied 22 healthy volunteers the opioid painkiller remifentanil and then studied the effect of the drug by changing the patients' expectations for the effect of treatment.

For the entirety of the study, the participants were positioned inside of an MRI brain scanner. An intravenous line was attached to them to administer the drug as well and stayed affixed the entire time.

Once this was set up, the researchers began the tests by giving the volunteers remifentanil but did not tell them. Then the researchers began applying heat to the leg of each volunteer until it caused self-reported pain; they positioned the heat at such a point that each participant rated their first dose of pain at 70 out of 100.

With the drug in their bodies, the average level of pain levels the participants felt dropped slightly from 66 points down to 55 on a 100-point scale. The researchers then informed the volunteers that the remifentanil was starting, even though they had already been getting the drug.

The results were dramatic: the average pain levels of the patients fell considerably, to 39 points.

Bingel's researchers studied the “nocebo” effect—when patients believe they are not receiving medication by are—by lying and telling the volunteers that they were going to stop receiving the drug and that they might start to feel more pain once more. Immediately, the pain levels the volunteers reported feeling rose rapidly again to an average of 64 points, despite the fact that the researchers continued to administer the same level of the painkiller.

MRI scans illustrated diverse brain activity in retort to the expectations the participants held concerning the pain relief. The researchers reported the MRI scans showed that areas of the brain’s of participants who believed they were getting painkillers were occupied and it was harder for pain signals to reach the brain or spinal cord.

"Our study provides evidence that the expectation of a drug's effect critically influences its therapeutic efficacy," said Bingel.

Experts said the results suggest that doctors may need to deal with beliefs of their patients concerning a treatment, whether positive or negative.

This study is published in the Feb. 16 issue of Science Translational Medicine.