Like a magician’s illusion, the placebo effect has the power to turn something fake or inert into something real simply through belief that it is real. But what is the placebo effect? Placebo comes from the Latin, placere, meaning “I shall please.” It describes a real phenomenon where something inert, like a sugar pill, has a measurable, beneficial effect; whereas its harmful counterpart has been named the nocebo effect. There have been numerous studies investigating the neural mechanisms of the placebo effect (e.g., Benedetti et al 2011). Strictly speaking, this effect is not just “mind over matter” alteration of human health, but anything that produces a non-zero effect for an otherwise fake or sham treatment. There are three important causes that also count towards the placebo effect, including random chance, statistical biases and regression to the mean.
The first non-physiologic cause is random chance. By mere coincidence, the control group of an experiment, often a placebo control in clinical trials, may appear to have had a beneficial (placebo) or harmful (nocebo) effect. Researchers should be especially suspicious if the sample size in the experimental groups are small. The only thing guaranteed by taking s random sample is that the expected group effect, which should be none for the placebo, will approach this value with increasing sample size.
A second contributing factor is a social expectation bias. If a patient is sick, and they expect treatment, the patients expectations will rise and may exaggerate their symptoms and responses in favour of a successful treatment (or not). Therefore, a biased effect is measured.
The last and likely largest cause of the placebo effect is regression to the mean, more simply put as “symptoms fluctuate with disease.” Take patients suffering from chronic pain, in which some days are better than others. Patients measured on a worse day, reporting worse symptoms, are more likely to report improved symptoms on another day when the pain is likely to be closer to the average. Under this effect, pain may be improved/worsened simply by measuring it at two different times and regardless of treatment. More importantly, this phenomena occurs with any naturally fluctuating process, which makes it possible to observe in nearly all clinical trials. This last effect is also demonstrated in double blind placebo-controlled trials which have a non-treatment arm, in addition to the placebo and experimental arms. The effects measured in both the placebo and non-treatment arms are the same or similar.
The placebo effect, and it’s harmful counterpart nocebo, are real and measurable effects. There is interest in teasing out the molecular mechanisms behind such effects, but there are also causes for a spurious effect, including random effects, biases and regression to the mean.
Benedetti, Carlino, Pollo. How placebos change the patient’s brain. Neuropsychopharmacology (2011).