Title: Exploring the placebo effect

Key words: physical, metaphysical, shamanism, science, mysticism, physicians, rationalism, antibiotics, placebo effect, physiological balance, imbalance,

Date: Jan 2002

Category: Materia Medica

Type: Abstract

Author: Bob Roehr






The placebo effect "is a riddle wrapped in a mystery inside an enigma," to appropriate Winston Churchill's language in describing the Soviet Union of Joseph Stalinís day. The National Institutes of Health in the USA is assembling a research agenda that may peel away some of the placebo's multiple layers of unknowns.

Exploring the placebo effect

The placebo effect is a concept that many biomedical researchers find disconcerting. It carries the stigma of "some unspoken and unacknowledged conspiracy between caregiver and patient, one pretending to help, the other pretending to get better," says Robert M. Rose, director of mental health at the John D. and Catherine T. MacArthur Foundation. "There is a presumption that the psychological is not quite real, that that which emerges from suggestion is just made up."

Separation of the physical from the metaphysical is a recent development. Over most of recorded time, the healing arts of shamans, mystics, and, eventually, physicians have treated the person as much as the malady. Their crude tools made it largely irrelevant to patient and provider whether success came directly from the potions they administered or their laying on of hands in administering them.

The distinction became an issue only with the ascendance of rationalism. It became important only with the mid-20th century development of antibiotics and the accompanying evolution of research as an endeavor separate from the practice of medicine.

Now one had to prove that the elixir produced the magic. For many, explanatory mechanisms became as important as the clinical benefits they conferred. And the effect known as placebo became both a yardstick and a nemesis.

One way that biomedical research sought to both prove and protect itself was through the randomized placebo-controlled trial, says Anne Harrington of the Department of the History of Science at Harvard University. But the placebo effect confounds this refuge of rationality. "So long as placebo was seen as noise, it probably didn't matter much," she says. Only when research began to measure very real physical effects of placebo did it come to be seen as a serious problem.

"To what extent are we addressing a culturally constructed problem [of the placebo effect] that was never an issue in any other culture in civilization except the one that modern medicine has created?" asks Ted Kaptchuk of Harvard Medical School. "In addressing this, I think that we are addressing the question, Are we burdened with an impoverished vision of healing?"

The quest to reunite shaman and science in the healing arts has led the National Institutes of Health (NIH) to delve into the myth, insight, and science surrounding the placebo effect. Its initial aim is to formulate an interdisciplinary research agenda to explore this terra mal cognita.

The placebo effect raises "fundamental questions about the practice of evidence-based medicine," says Josephine Briggs, director of the Division of Kidney, Urologic, and Hematologic Diseases at NIH. It may be additive in the sense of having its own value, either alone or in synergistic combination. It may be modulatory, both positively and negatively, in terms of changing the real effect of what is considered to be the active intervention.

"Can the placebo effect occur without placebo?" muses Daniel Moerman of the Department of Behavioral Sciences and Anthropology at the University of Michigan at Dearborn. "Of course," he responds to his own question. "Words are not inert; they can have profound effect." He cites a study in England that compared a well-known over-the-counter analgesic, a generic aspirin, and placebo. Belief that one received the branded product brought greater headache relief, regardless of what was dispensed.

Moerman calls this "a meaning response." He argues that neither patients nor doctors are blank slates, that each brings a vast matrix of expectations with them, both in terms of a cultural context and knowledge and expectations of the planned intervention.

For example, in Chinese cosmology every fourth year is an "earth year" and those born during it are said to be particularly vulnerable to tumors. One study found that Chinese-Americans living in California who were born in earth years died significantly earlier of tumors than those with the same medial condition born in other years, while non-Chinese Californians showed no variability by birth year. The reduction in life span correlated with the strength of commitment to traditional Chinese culture.

Moerman points to other studies indicating that "as new drugs come along, old ones become less effective." The intervention does not matter - from pills to surgical procedures, newer seems to be better. He says the effect often is not because the old procedure or drug begins to fail but because physicians invest in the notion of progress. They transfer their enthusiasm to the new procedure or drug, which may be passed on to the patient and shade the physician's evaluation of the response.

Moerman suggests that adherence to a therapeutic regimen may be a marker of patient expectations. Because adherence correlates with a successful outcome, changing expectations may change outcomes. The prophecy becomes self-fulfilling.

He believes that understanding the cultural context and expectations of those involved in the healing dynamic can "help us recognize meaning embedded in our own medical system," meaning that we tend to overlook.

Steven Hyman, director of the National Institute of Mental Health, says, "We are not going to be able to grapple very well with issues of potency, reliability, and time course [of interventions] until we begin to dig into some of the mechanisms underlying these responses."

He is looking to "ultimately bring together psychological explanations and underlying neural mechanisms" of action in response to interventions. "Expectancy might be a rather transient phenomena," he posits, "depending upon the immediate context, whereas conditioning, true learning, means that there has been synaptic remodeling which will last a lifetime."

"We need statistics of nonspecific effects," says Kaptchuk. "When we say that a clinical trial has a 30 percent placebo effect, do we mean that 30 percent of the people have the identical response as if they were on the drug? Or do we mean that an undetermined number of people had a response that was less than the drug?"

Robert Ader of the University of Rochester Medical Center is "not sure" that the placebo effect can be studied in healthy individuals. A body in physiological balance differs from that same body when it is in a state of imbalance.

Just as vitamin C can alleviate scurvy in a person deficient in that vitamin but have little effect upon a person with sufficiency, so too, some placebo response may occur only in a deficient condition of the ill. Adler's doubts extend to staging of disease, where the effect of both placebo and active intervention may differ greatly between chronic and acute states.

So how can one study the placebo effect? Harrington believes that these "shy fauna that live and lurk in the territory of human psychobiological functioning" perhaps could be observed by looking closely at historical data to try to discern patterns of where placebo has had its most powerful effects.

"If you could identify and isolate the biochemistry underlying the placebo effect and make it into a pill, would it still be a placebo effect?" she asks.

Harrington's question reinforces the sense that the placebo effect is a black box containing all those things that we do not understand and cannot attribute to other causation. As artifacts hidden within that container become better characterized, measured, and manipulated, they will shed the mantle of placebo and come to stand on their own.

Thus, NIH's exploration of the placebo effect is not a reversion to shamanism at the expense of scientific rigor. Rather, it is the frontier of understanding complexity in the real world of biomedical cause and effect. It is likely to remain so as we parse the unknown into finer gradients of what becomes known.

Bob Roehr is a freelance journalist and medical reporter based in Washington, DC. He writes frequently for the monthly journal of the International Association of Physicians in AIDS Care.


National Conference Explores the Placebo Effect - a brief article about the recent NIH meeting on the placebo effect. From the January 23, 2001 issue of the NIH Record. Also see the NIH's meeting site, The Science of the Placebo.

The Placebo Prescription and Sham Surgery Returns as a Research Tool - two recent articles from The New York Times. Free registration required for access.

The Placebo Effect - an interview with Walter Brown of Brown University and Ted Kaptchuk that originally aired on January 10, 2000 on The Connection. Requires RealPlayer.

The Mysterious Placebo Effect - discusses the history of the word placebo and placebo trials, as well as recent studies to understand how they work. From the July/August 1999 issue of Modern Drug Discovery, an American Chemical Society publication.

Placebo Effect Could Skew Tests of New Therapies - warns against using patients' self-assessment of well-being as a clinical trial outcome. From the Office of Public Affairs at Duke University.