Placebo Effect: All in the Brain

August 29, 2005

Pharmaceutical Executive

Pharmaceutical Executive, Pharmaceutical Executive-08-30-2005, Volume 0, Issue 0

Scientists at the University of Michigan found a brain mechanism that increases the release of pain-fighting endorphins when the subject was given a placebo. The implication? Better clinical trials, and maybe, new methods of pain relief, researchers say.

Scientists at the University of Michigan found that giving placebos for pain treatment can cause the brain to release natural painkillers that actually diminish the unpleasant sensation and the associated stress.

    According to a study published in the August 24 issue of the Journal of Neuroscience, nine out of the 14 participants’ brains responded to being told that they were receiving pain medication by releasing pain-fighting endorphins, even though all of the subjects were given placebos.

    “The effects of our own thinking are more pervasive and deeper than we even thought,” Tor Wagner, assistant professor of psychology at Columbia University, said in response to the study.

    The nine subjects who responded to the placebos reported that they felt a decrease in pain intensity and in the unpleasantness of the sensation, lead author Jon-Kar Zubieta explained. They also indicated a decrease in emotional responses to pain, including fear and irritability.

    In addition, Positron Emission Topography (PET) scans of the subjects showed that the brains of these nine reacted to the expectation of pain relief by releasing endorphins. This was observed in four different areas of the brain, according to Zubieta – the left dorsolateral prefrontal cortex, the pregenual rostral right anterior cingulated, the right anterior insular cortex and the left nucleus accumbens.

    These regions are also involved in other complex processes besides pain management, which may play a part in reducing the stress of pain, he explained.

    “Placebo effects are physiology, not just psychology,” Zubieta said.

    He described the reaction to placebos as graded, not black and white as is often indicated when the effect is observed in clinical trials. Zubieta indicated that future studies should try to determine the reasons for different levels of response to placebo such as emotional state, brain function and genetics.

    Zubieta thinks that understanding the placebo effect could help both scientists and doctors. First of all, it could aid clinical researchers in improving their interpretation of trial results. Alternatively, Wagner and Zubieta both suggested that pharma companies could develop a product that harnesses the placebo effect by targeting the brain pathways involved in this phenomenon.

    Additionally, physicians could maximize the impact of real drugs by using the mechanisms of the placebo effect to encourage their patient’s brains to provide additional relief, Zubieta said.

    Wagner believes understanding the placebo effect would change the way doctors interact with patients about the medicines they prescribe. He said these findings as contribute to a scientific dialog between doctors and sociologists concerning “how to think about pain, healing and health.”

    But Ted Kaptchuck, assistant professor at Harvard School of Medicine, said the clinical impact of understanding the placebo effect is “still a long way off.”

    Kaptchuck praised the Zubieta paper for tying several lines of enquiry together. But he said that more work needs to be done. He thinks that researchers should examine the placebo effect in patients with actual clinical problems. The Zubieta study used healthy volunteers and injected salt solution into their jaw muscles to cause pain. Kaptcuck also is interested in studying the placebo effect on subjects with long-term pain.

    He recently completed and submitted an 8-week study on the placebo effect in a clinical population. It has not been published yet.

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