Just as a placebo can fool the mind and bring about real positive effects on the body, expecting that a drug will not work, or that you're not receiving a drug when in fact you are, can negate the effects of a powerful painkiller, according to a new study.
Researchers from the United Kingdom and Germany studied brain scans of 22 study participants in pain as they were given a painkiller, but varied in what they told the participants about what they were receiving. They found that telling participants they were receiving no drug — even though they actually were — completely eliminated the painkiller’s effectiveness. On the other hand, when patients received and were told they were receiving a powerful painkiller, they saw their pain relief double.
"The overall treatment outcome is substantially modified by the patient's individual expectations and prior experience with treatments and physicians," said Dr. Ulrike Bingel, a neurologist at University Medical Center Hamburg-Eppendorf and one of the study authors.
The study was published today (Feb. 16) in the journal Science Translational Medicine.
Of pain and placebos
In the experiment, the researchers attached a thermode — a device designed to deliver painful heat — to each participant's calf, and set it to give pain at a level of 70, from the subject’s perspective, on a scale of 1 to 100. They also injected each participant with a solution.
On the first trial, participants were given a saline solution, to establish a baseline.
The participants were then given remifentanil, a potent and quick-acting painkiller, but told the solution was a placebo. They reported feeling slightly less pain — rating their pain at a level of 55.
Next they were given remifentanil and told they were being given a painkiller. This dropped their pain down to a 39 — even though there was no real difference from the previous trial.
Finally, they were again given the painkiller, but told they were receiving no drug. They reported their pain to be level 64, which was not significantly different from the baseline pain they reported when receiving only saline.
Tellingly, different areas of the brain lit up on functional magnetic resonance imaging (fMRI) scans when patients were told they were being given a painkiller than when they were told they were not.
Remifentanil is a fairly powerful opiod, and therefore was a good choice for the study, said Dr. Randy Gollub, an assistant in neuroscience in radiology at Massachusetts General Hospital, who wrote an editorial accompanying the study but was not involved in the research.
"There's nobody you give remifentanil to who won't feel less pain," she told MyHealthNewsDaily. "Here is a beautiful paper showing we can double or half the potency of the drug."
While many have thought the placebo effect applied only to placebos, the idea that the same effects can take place with actual medicines, "is not a phenomenon that's embraced broadly in clinical medicine and clinical research," Gollub said.
But just as important as the fact that there was an enhancement of the drug may be how it happened.
"They don't know for sure that the drug works better, they know that the overall effectiveness is better when you know you're getting a drug," said Tor Wager, director of the Cognitive and Affective Control Laboratory at the University of Colorado at Boulder, who was also not involved with the study.
Wager said that it is unclear if the drug had its typical effects, and the placebo effect took place on top of that, or if the combined effect of the two yielded a different result.
The study looked at pain, and the results would likely be different when looking at drugs that have less subjective outcomes, such as antibiotics used to treat infection, he said.
"Nobody has ever demonstrated that a placebo elicits any kind of immune response that is useful in fighting bacteria," Wager said. "It would be amazing if that were the case, but it's not that likely."
How expectations may affect drug trials
The effect that a treatment can have outside of the medication itself is important to watch in future studies, researchers said.
Clinical studies should aim at identifying how to optimally enhance the effects of a drug, rather than treating expectations as a confounding factor, Bingel said.
In other words, future research may need to take into account not only the drug, but the best way to ensure a patient feels good about the course of treatment.
"It's challenging, but vitally important to make sure a research project has a good handle on what sort of sources of placebo effect there might be," said Dr. Ian Cook, director of the UCLA Depression Research and Clinic Program. "What this study tells us is that what we believe, what we think, can have a tremendous impact on what our brain does and how it processes information."
Doctors working with patients, Cook said, should take this into account.
"If you're a clinician, encourage patients to be optimistic. They may experience better outcomes," he said.
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