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Although the term placebo effect might appear logically to refer to "the effect produced by a placebo," that definition is not in fact the one most commonly used. It would be more accurate to define the placebo effect as "the mind-body interaction triggered by medical treatment, historically discovered as a result of placebo use." That is, medical science may first have learned about the potential impact of the patient's mental state on healing by observing the effects of placebos ("dummy" or "sham" therapies thought to be lacking in any ingredients capable of producing bodily changes by chemical or physical means). If patients' bodies and symptoms were altered in impressive ways after the administration of placebos, the absence of any chemical explanation for the change suggested that it could only be by means of the patients' minds that such changes occurred. Once this basic observation is made, one may go on to divorce the patients' mental state from the use of dummy or sham remedies. Virtually any aspect of the encounter with a physician or other health worker could stimulate the requisite mental state, whether that state is one of expecting that one will get better, feeling trust in the caregiver, or whatever the precise psychological mechanism may be. It is in keeping with most modern usage to define placebo effect as "a change in a person's health status attributable to the symbolic or emotional impact of a healing intervention."

History

Ancient Greek medicine and the humoral medicine of the Middle Ages and Renaissance simply took for granted that words had the power to both cause or cure disease and that the mind and the body were constantly interacting to determine the individual's state of health. The earliest known reference to deliberate use of a placebo appears in a 1580 essay by Montaigne (1533–1592) describing a hypochondriac who was cured by an enema administered with great fanfare but without any substance actually being injected into the body. It is almost certain, however, that the use of placebos in medicine antedates this essay, probably by many centuries.

Medical science underwent a more materialistic turn and began to ignore the mind during the nineteenth century, but even then, citations appeared in the medical literature testifying to the power of placebos, and to the imagination generally, to alter disease. Placebos were frequently administered in the nineteenth century, in part because the profession lacked more effective medicines for most diseases.

Benjamin Franklin (1706–1790) was one of the first to use a single-blind technique in experiments on the power of mesmerism (hypnosis) conducted in 1785. Franklin was able to show by concealing the hypnotist behind a curtain that subjects' reactions were based on what they thought was happening and not on what was actually happening. Medicine increasingly demanded a blind technique when investigating "unconventional" or "quack" remedies in the nineteenth century but resisted the idea that conventional medical drugs and other remedies ought to be subjected to the same methods. After World War II, medical scientists became more aware of the potential for bias to skew research results if either the subject of the experiment, or the physician observing the experiment, knew who was receiving the "true" medicine, so the double-blind design, with neither party knowing which subject got the study medication and which got the placebo, gradually was adopted as the standard of valid research. Thus, precisely when placebos were less often used in medical practice (because so many powerful new drugs were available), placebos began to be used much more often as a research tool.

Modern medical ethics demands frank disclosure to the patient of the nature of any treatment administered. This, in most cases, rules out the deceptive use of placebos in therapy. But ethics does not rule out the attempt to elicit a placebo effect by creating a positive emotional environment during interaction with the patient. After largely dismissing the mind for many decades as largely unimportant and resistant to scientific study, modern medical science has developed a renewed interest in understanding the mechanisms by which the placebo effect might work. In 2001, the U.S. National Institutes of Health announced a new research program specifically aimed at understanding the mechanisms of the placebo effect and helping practicing physicians to enhance the effect.

Scientific understanding

Two psychological mechanisms appear to contribute to the placebo effect: expectancy (believing that a positive bodily change will occur) and conditioning (being in circumstances that, in the past, produced a positive bodily change). Evidence is accumulating that expectancy of pain relief can produce the release of endorphins, naturally occurring morphine-like chemicals in the brain that produce analgesia. In one study, when patients in pain following surgery were given a visible injection of a narcotic painkiller into their intravenous tubing, they experienced twice as much pain relief as when the same drug was given by hidden injection and the patient was unaware of receiving the drug. When naloxone, a drug that antagonizes the effects of endorphins, is administered to patients in the same manner, the placebo effect can be reversed.

Modern brain imaging techniques promise to expand the understanding of the mechanisms of the placebo effect. Using positron emission tomography (PET) scanning, for instance, patients experiencing a placebo effect in Parkinson's disease were shown to be manufacturing more dopamine in their brains, indicating that the placebo effect in Parkinson's may work by the same biochemical mechanism as the standard drug therapy.

Amidst new findings on how the placebo effect works, some skeptics continue to question whether the effect even exists. A systematic review of 114 randomized double-blind clinical trials (Hróbjartsson and Gøtzsche, 2001) concluded that there is no good evidence that administering placebos in the context of scientific trials produces any significant change in the subjects. (The authors did not intend their findings to address whether the placebo effect might exist in actual medical practice.) The methods used in this review have been challenged by placebo-effect advocates. Regardless, an important lesson from skeptical research such as this is that there are many mimics whose effects must be carefully separated from true placebo effects. Perhaps the most common mimic is the natural history of the illness, or the body's inherent healing powers. Many older studies that are quoted as confirming a powerful placebo effect in fact failed to distinguish between the patient's getting better because the illness was self-limited and the body's defenses were capable of eliminating it (as is the case with most common viral illnesses) and improvement that truly depended on the patient's mental or emotional state.

Implications for religion

Placebo effects may be of greatest interest in one category of so-called complementary and alternative medicine (CAM): methods of healing that rely particularly on religious faith or religious practices.

Religiously-based healing might be thought, by believers, to occur in one of two ways. In what one might call the natural route, faith, prayer, or other religious practices may be seen as stimulating the same chemical and physical processes in the human body as would be produced by any other system of medicine or healing. In what one might term the supernatural route, faith or prayer comes directly from a divine source and does not depend solely upon processes that science can measure or understand.

In religious healing by the natural route, the placebo effect could account for some and perhaps all of the healing observed. Faith and prayer may produce positive expectancies, and religious ritual may be a powerful source of psychological conditioning. So long as one believes that the human mind is part of the natural world, molded by the same creator who is responsible for any other healing modality, it seems logical that one would seek to harness the powers of the mind as part of whatever healing occurs. On this understanding the placebo effect becomes simply one means by which faith can heal.

In religious healing by the supernatural route, it might appear by contrast that if one could show that a placebo effect were occurring, that would exclude the possibility of the postulated healing effect. This seems particularly true for studies of intercessory prayer, in which believers claim that patients can be healed when people pray for them unbeknownst to the patients themselves. By definition, no emotional or mental effect can be generated if the subjects are completely unaware of the intervention. Therefore, to claim that the results of intercessory prayer are a placebo effect would be the same as denying that intercessory prayer works.

Another important implication of the placebo effect for religious healing is shared with other types of CAM: the design of appropriate comparison groups to conduct reliable research. What counts as adequate evidence that any form of CAM, including religious or faith healing, works? Some scientists reject all CAM out of hand as based on superstition and quackery, but more careful scientists are willing to accept CAM insofar as it can be shown to be effective in rigorous scientific studies. The question then arises as to what counts as adequate scientific "rigor" given the subject matter under study.

One way to approach this concern is to view science as a highly systematic way to show with a high level of probability that one explanation is the correct explanation for the phenomenon in which we are interested. Showing this requires that we consider all other plausible explanations and find ways to exclude them, so that we are left with only one explanation that appears to be correct. This is what it means in general terms to have a controlled study. It follows from this analysis that having a placebo or sham-treatment control group is one good way to eliminate several plausible explanations for healing. A placebo control group can eliminate the placebo effect, the natural course of illness, and a number of chance statistical associations as reasons why the subjects receiving the healing intervention got better. Because the placebo control is useful for many study purposes, it is tempting to assume that the only valid scientific study is one with a placebo control, but this would be mistaken. Depending on the question being investigated and which alternative explanations are most plausible, there may be other scientific methods to exclude the alternative explanations with a high degree of reliability. In many possible studies of religious healing, the usual methods to assure scientific rigor will simply not be possible. It is hard, for example, to imagine a population of both believers and nonbelievers agreeing to be assigned randomly to receive real or sham faith-healing.

See also MEDICINE; MIND-BODY THEORIES; SPIRITUALITY AND HEALTH

HOWARD BRODY