As an article on placebos in an edition of “Lancet” in 2010 tells it, the term placebo, derived from the Latin verb placere (to please), has its origin in religion. Apparently, a fourth century theologian, St. Jerome, erred in his translation of the verb in the 116th psalm. Instead of translating the Hebrew phrase, “I shall walk before the Lord,” he wrote: “I will please the Lord.” (“Placebo Domino in regione vivorum,” so I am told). In the Middle Ages, hired mourners chanted this line repetitively, and thus became known as “placebos,” to describe their feigned behavior. The first described use of placebo controls was recorded in the 16th century. At the time, exorcism was widely practiced. In an effort to gain control over this activity and to discredit some of its practitioners, Catholic clergy performed sham exorcism procedures.

Medical interest in placebo effects did not occur until the end of the Second World War, when clinical investigators adopted the use of randomized controlled trials. Enlightened researchers realized that the appropriate approach to the study of efficacy (and safety) required the drug under study to be compared to an active comparator arm, which generally consisted of a placebo therapy. These clinical investigators noted something quite unexpected: Regardless of the drug or treatment being studied, about one-third of patients assigned to the placebo control arm responded favorably.

While this phenomenon certainly confounds the process of determining the efficacy of a given therapy, the placebo effect is a fundamental part of the healing process. In fact, this effect is considered by some authors to be etched in our brains as a result of evolution, since it may offer an evolutionary advantage to human beings by providing a critical pathway for promoting optimal health, according to Walter A. Brown in his book, “The Placebo Effect in Clinical Practice.” Not surprisingly, the placebo effect has been observed more commonly in the fields of psychiatry and psychology, where some consider psychotherapy to be the ultimate placebo therapy. The placebo effect has had a huge impact on pain therapy research, as it has been found to modulate the response to pain by increasing brain endorphin and endogenous opioid production, similar to what has been observed in the “runner’s high.” In a study of rectal pain published in the journal “Pain” a couple of years ago, functional magnetic resonance imaging (fMRI) observed that the expectation of pain relief could substantially change the perceived degree of pain. This effect was modulated through activation of pathways in the prefrontal and somatosensory cortex and the thalamus. This and other studies seem to provide the biological basis for the placebo effect, giving scientific support to an observation by the late astronomer Carl Sagan, who almost 20 years ago said: “A placebo works only if the patient believes it’s an effective medicine. Within strict limits, hope, it seems, can be transformed into biochemistry.”

As healthcare professionals we now have an excuse to slow up for a moment or two, to not be hopping from examination room to examination room. There is indeed, at least in some instances, a biochemical basis for hoping and believing. I have written blogs about attitudes towards patients, and the importance of the expression of empathy. Our words, attitudes, and behaviors play dominant roles in both the doctor–patient interaction and in the placebo response. It is always about being nice, but add on to that that it is also about making a patient physically better. There must be some evolutionary reason for the emergence in man of altruism, empathy, and compassionate behavior. Dr. Benedetti postulated last year in the journal “Physiological Reviews” that facial expressions are likely to have evolved for eliciting medical attention from others.  It is as if we are characters in some evolutionary puppet show, and so much does work, we do feel better and make others better, as long as we don't forget our parts.

We should respond not just with medical attention, but also with genuine personal attention.  We are not simply prescribers of medicines, we are advocates for the placebo effect.

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