Placebo Effect: Expensive Sham Medical Treatments Cause Worse Side Effects Than Cheap Ones

Tinnermann and fMRI
Alexandra Tinnermann and her colleague set up a research subject to receive a functional magnetic resonance imaging scan for her research on how the strength of a "nocebo" effect can change based on perceived price. Courtesy of Alexandra Tinnermann

Many of us are familiar with the placebo effect—a fake pill, for example, that has an effect on us because we think it's real—but the phenomenon of experiencing side effects from a placebo is lesser known. It turns out that this effect is heavily tied to how much the fake pill cost: the more we spend, the worse we feel.

In a study published in Science Advances on Thursday, nearly 50 young, healthy people were told the cream they were testing would relieve itches. Participants were also told that the price and the side effects may differ between the creams. However, the creams were exactly the same and had no medicinal ingredient at all.

During a series of pain tests after the cream had been applied, people said they felt nearly 30 percent more pain when the cream they got looked expensive.

The experience of negative side effects from placebos has a separate name—"nocebo." Prior research has uncovered the role that nerves in the spinal cord play in triggering sensations of pain that stem from our imagination, for example. How the perceived price shapes our experience of a sham treatment has also been investigated. But the new study puts all these pieces together using a real-time brain scanning technique called functional magnetic resonance imaging (fMRI) to track where the perceived pain was being processed in the brain and the spinal cord.

"Usually you would record activity either in the brain or in the spinal cord," lead researcher Alexandra Tinnermann tells Newsweek, "but not at the same time."

Tinnermann and cream application
Alexandra Tinnermann applies cream to a woman's forearm. Her research used these creams to determine how people perceived side effects of sham treatments. Courtesy of Alexandra Tinnermann

The finding provides important insights about real medications. For example, how physicians present different treatments could alter the experience patients then have, Tinnermann says. "I think physicians really underestimate their power and how they could influence the recovery or the development of side effects." A commentary that accompanied the findings also noted that discussing the potential side effects of an experimental drug with people participating in a clinical trial—a key part of getting informed consent—may make these kinds of nocebo effects more likely.

The boxes that she and the rest of the team at University Medical Center Hamburg-Eppendorf used were Tinnermann's own design. She created the "products" after looking for patterns in pharmaceutical packaging and reading studies about product design. "White and lighter colors are associated with rather cheap products and darker colors are more associated with expensive ones," she said. As part of the study, she asked subjects who didn't use the fake creams how much they thought the medications cost. On average, people said the cheaper one would cost about $12. The more expensive one got an estimated price tag of nearly $18.

These are the "medicated creams" that Alexandra Tinnermann, a researcher at the University Medical Center Hamburg-Eppendorf, used to test how perceived price might change how much people felt side effects of these sham treatments. Courtesy of Alexandra Tinnermann

A. Vania Apkarian, a pain researcher at Northwestern University who also uses brain imaging techniques, but was not involved in the research, says that the study advances our understanding about how our biases influence our healthcare. "We have assumed for many years that the brain would control pain perception at many different levels and that expectations would change those things," he tells Newsweek. This study is the first to show the entire circuitry linking expectations and perceptions, Apkarian explained.

Pain isn't just felt in the brain; the sensation of pain is also transmitted up and down nerves running through the spinal cord. This entire descending pain pathway is associated with the placebo and nocebo effects, and Tinnermann and her team found that the level of activation in areas involved with the pathway was correlated with the amount of pain people said they were feeling.

However, that entire circuit could be markedly different for the people for whom it matters most—patients in actual pain. Tinnermann and her team tested only healthy subjects, which she and Apkarian noted could limit the generalizability of the findings.

"What we learn from these healthy subjects does not necessarily apply to the clinical population where these things are more relevant," Apkarian says. Pain patients have different brain circuitry, for example, because of their experiences. Tinnermann also says she would have liked to include even more people in the study if she'd had the resources to do so.

Nevertheless, these limitations "do not diminish the value of the study," Apkarian says. "The overall concept is quite elegant."