It is well known that placebo effects can alleviate symptoms of illness: for this reason, new drugs, for example, should always be tested in comparison with a placebo treatment in order to determine their actual effectiveness. However, even a known effective therapy can be improved if the treating physicians additionally increase positive expectations regarding the active ingredient. Researchers from the SFB/TRR 289 “Treatment Expectation” have demonstrated this in an experimental study.
A total of 124 healthy volunteers received either ibuprofen treatment or a placebo in the experiment, combined with either a positive or neutral explanation from the treating physician. All participants were then injected with the substance lipopolysaccharide, which causes inflammation-related disease symptoms. Up to six hours after the injection, the researchers measured several inflammation markers and recorded the physical symptoms of the participants, such as pain or swelling, as well as psychological symptoms such as feeling low or feeling ill.
Positive expectations alleviated the symptoms of illness – and enhanced the effect of ibuprofen
The result: As expected, those treated with ibuprofen showed fewer symptoms of inflammation than those in the placebo group. However, even a placebo treatment alone was able to alleviate the symptoms – when combined with a positive explanation from the doctor. And the effect of ibuprofen was significantly greater when the doctor had previously raised positive expectations of the medication.
These improvements were particularly noticeable in symptoms reported by the participants themselves, especially so-called affective or psychological symptoms. In contrast, the doctor's explanation had no influence on the physiological markers of inflammation – an indication that expectation effects work in a different way than directly influencing the immune response.
This study, in which our projects A04, A10, and A11 participated, shows for the first time that placebo effects can also increase the benefits of active ingredients in cases of inflammation. This is an important finding for healthcare professionals: even small changes in the way patients are addressed give a positive connotation to a therapeutic measure, which can significantly increase the success of the therapy.
Original work:
Schmidt, J., Reinold, J., Rohn, H., Schedlowski, M., Engler, H., Elsenbruch, S., & Benson, S. (2025). Placebo effects improve sickness symptoms and drug efficacy during systemic inflammation: a randomized controlled trial in human experimental endotoxemia. BMC medicine, 23(1), 455. https://doi.org/10.1186/s12916-025-04292-8
"Ibuprofen works even better with the right words" – Foto: freepik