Karolinska study shows placebo can be activated unconsciously

A new study by scientists at Karolinska Institutet and Harvard Medical School shows that the placebo effect - i.e. the effect of positive expectations on a medication or treatment - can be activated automatically outside of conscious awareness. This contradicts the common opinion that placebo responses are related only to conscious beliefs or thoughts.

The results, which are published online first in Proceedings of the National Academy of Sciences (PNAS), also include the negative placebo effect, called the nocebo effect.

"The process is likely to begin, for example, in a room with medical equipment, where the mind may implicitly make associations to previous hospital visits and thereby anticipate positive treatment outcomes in response to these contextual cues", says Karin Jensen, who led the study. "We are talking about an automatic reaction in the central nervous system that may lead to considerable changes in patient's health outcomes."

In the current study, the scientists have created a unique experimental model which shows that this 'cognitive unconscious' could produce reduced pain (placebo responses) and increased pain (nocebo responses). The study includes two experiments in which the responses to thermal pain stimuli were assessed. In the first experiment, clearly visible cues for high and low pain where used. The second experiment in a separate group of subjects, assessed whether the responses could be triggered by non-conscious (masked) exposures to the same visual cues. A total of 40 healthy volunteers (24 female, mean age 23 years) were investigated in a laboratory setting.

Participants rated each pain stimulus on a numeric response scale, ranging from zero (no pain) to one hundred (worst imaginable pain). Significant placebo and nocebo effects were found in both experiments, i.e. it didn't matter if the participants experienced clearly visible or non-recognizable stimuli. According to the scientists, this indicates that mechanisms responsible for placebo and nocebo effects can operate without conscious awareness of the triggering cues. In other words, it is not what a person think will happen, it is what the non-conscious mind anticipates, despite any conscious thoughts.

"Such a mechanism would generally be expected to be more automatic and fundamental to our behavior compared to deliberate judgments and expectations", says Karin Jensen. "These findings can help us explain how exposure to typical clinical environments and routines can activate powerful health improvements, even when treatments are known to be ineffective."

The scientists will now further investigate placebo and nocebo mechanisms by using tools such as neuro-imaging. Karin Jensen is affiliated to both Harvard Medical School and Osher Center for Integrative Medicine at Karolinska Institutet. The work was supported by funding from the Swedish Society for Medical Research, the Swedish Council for Working Life and Social Research, the National Center for Complementary and Alternative Medicine (NCCAM), and the National Institute on Drug Abuse.