Can open-label placebos work even when we know they are “inert”?

For decades, it was believed that placebos only worked when administered covertly. Informing a patient that they would take a pill with no active ingredient seemed absurd. However, recent studies show that so-called open-label placebos (administered with full honesty) can have real effects.

A team led by Michael Schaefer investigated this phenomenon in a randomized controlled trial. Healthy participants were exposed to emotionally disturbing images and received a nasal spray labeled as a placebo or an identical spray without that indication. The aim was to test three possible mechanisms: the administration ritual (self-applying the spray or having it administered by the investigator), positive expectation, and belief in placebos.

The results suggest that open-label placebos reduced emotional discomfort compared with the control group. The mode of administration made no difference. Initial positive expectation was not associated with an actual reduction in emotional discomfort, but it was linked to the subjective perception that the treatment was effective. Belief in placebos, however, was associated with a greater reduction in emotional stress. In other words, it is not enough to have a conscious expectation that it will work; the data indicate that unconscious processes seem to play a central role in the open-label placebo effect. Interestingly, people who believe in homeopathic treatments did not show greater benefit, although they reported more positive expectations.

The study reinforces prior evidence that open-label placebos can alleviate symptoms even when we know they are “inert.” How? Probably through unconscious mechanisms linked to cognitive, social, and physiological factors that are still not well understood. The data suggest that honesty does not nullify the placebo effect, which could open the door to safe and ethically acceptable therapeutic approaches. This study was published in the scientific journal Scientific reports, in the article Roles of administration route, expectation, and belief in placebos in a randomized controlled trial with open-label placebos, as a part of research project 98/22 - Neural correlates of open-label placebo effects in emotional distress, supported by the Bial Foundation.

ABSTRACT

Recent reports challenge the view that placebos need to be given in deception. Numerous studies report remarkable effects when giving placebos honestly in an open way. However, the mechanisms of open-label placebos still remain to be cleared. For example, while expectation is often regarded as an important mechanism for concealed placebos, it is unclear whether this process may also account for open-label placebo effects. Thus, alternative theories based on, for example, the embodiment theory are also discussed. Here we examined possible mechanisms of open-label placebos including administration route (to address rituals or sensorimotor embodiment mechanisms), expectation, and belief in placebos. Healthy participants viewed emotional distressing pictures and were given an open-label placebo beforehand or were in the control group. Results replicated previous studies by showing that participants in the open-label placebo conditions felt less emotional distress. Route of administration did not affect the placebo response. Treatment expectancy did not predict the placebo effect but was linked to the strength of the placebo effect that participants self-reported (which was not related to the actual placebo effect). Belief in open-label placebos was related to the strength of the placebo effect. Interestingly, an affirmative attitude towards homeopathic treatments was linked to a positive treatment expectation, but not to the actual placebo effect. We discuss the results with respect to different theories explaining open-label placebo mechanisms and argue that open-label placebos may work predominantly in an unconscious way.