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placebo

placebo (pləsē´bō), inert substance given instead of a potent drug. Placebo medications are sometimes prescribed when a drug is not really needed or when one would not be appropriate because they make patients feel well taken care of. Placebos are also used as controls in scientific studies on the effectiveness of drugs. So-called double blind experiments, where neither the doctor nor the patient knows whether the given medication is the experimental drug or the placebo, are often done to assure unbiased, statistically reliable results. A traditional placebo's lack of side effects, however, often identifies it, so an older drug is sometimes used in drug tests instead of or in addition to a placebo.

The "placebo effect" is an apparent improvement in health due not to any treatment but only to the patient's belief that he or she will improve (as by taking a dummy pill that is thought to be a cure). A report released in 2001, however, reviewed 114 studies where use of a placebo was compared to both treatment and no treatment and found no placebo effect with respect to measurable medical conditions, such as blood pressure and cholesterol levels. An opposite, or "negative placebo effect," has been observed when patients believe their health will get worse.

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placebo

placebo A treatment which has no effect, and is administered to a control group in experimental research, in place of a treatment whose effects are being studied. This usually happens only in medical research; in social research, control groups are rarely offered a placebo experience or treatment.

In the medical context, a substance lacking known pharmacologically active ingredients is given to the sick in order to please them; that is, for possible beneficial effects arising from faith in the powers of treatment (the placebo effect). Placebos are also widely used as controls in evaluating the therapeutic efficacy of the active components of new drugs. Conventionally, the experimental treatment is given to cases selected at random, with the ineffective placebo given to all other cases, even though they are suffering from the same illness. In the ‘double blind’ situation, even the person administering the treatments does not know which is which, as the medicines are made to look the same, to prevent him or her inadvertently communicating their knowledge to recipients.

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placebo

pla·ce·bo / pləˈsēbō/ • n. (pl. -bos) a harmless pill, medicine, or procedure prescribed more for the psychological benefit to the patient than for any physiological effect: his Aunt Beatrice had been kept alive on sympathy and placebos for thirty years | [as adj.] placebo drugs. ∎  a substance that has no therapeutic effect, used as a control in testing new drugs. ∎ fig. a measure designed merely to calm or please someone.

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placebo

placebo (liturg.) vespers for the dead. XIII. First word of the antiphon to the first psalm in the office: ‘Placebo Domino in regione vivorum’ (Psalm 114: 9) I shall please the Lord in the land of the living.

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placebo

placebo (plă-see-boh) n. a medicine that is ineffective but may help to relieve a condition because the patient has faith in its powers. New drugs are tested against placebos in clinical trials.

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placebo

placebo a pill, medicine, or procedure prescribed more for the psychological benefit to the patient of being given a prescription than for any physiological effect.

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Placebo

Placebo

Punk rock band

For the Record

Selected discography

Sources

The London-based trio known as Placebo takes pride in creating provocative music. We like to provoke strong reaction in people, bassist Stefan Olsdal admitted in an interview with the iMusic.com website. Indifference is something we try to avoid. Sometimes that leads to confusion, or anger, or interestbut you can never really predict the outcome. And forthose who follow up-and-coming pop-rock bands, figuring out Placebo did prove challenging at first.

Based on appearances alonefrontman Brian Molko favored an androgynous look with heavy dark makeupreviewers most often dubbed Placebo a goth-rock ensemble. But after the release of the bands eponymous debut in 1996, followed by 1998s Without You Im Nothing, pop enthusiasts discovered that there was more to Placebo than meets the eye. Rolling Stone writer Chuck Eddy, for instance, asserted, Placebo are the latestand toughestin the recent line of English pretty-boy guitar-glam bands ([London] Suede, Supergrass, Mansum, Rialto, Elcka). Soon, the band earned a reputation for their eclectic songcraft, as well as for their ambiguity and uncertainty, and also gained admiration from such accomplished musicians as R.E.M.s Michael Stipe, U2s Bono, David Bowie, and Marilyn Manson, all of whom Placebo claimed as friends.

Gender-bending lead singer Brian Molko first met Swedish-born bassist/guitarist/keyboardist Stefan Olsdal while attending school in Luxembourg. However, even though both students shared the common interest of music, the pair didnt become fast friends. Olsdal was a jock and played sports, on the one hand, while on the other hand, Molko was a self-described loser. Although they never hung outtogether much during their school days, the two did meet up again by chance years later in London and decided to form a band. Together, along with drummer Robert Schultzberg, Molko and Olsdal formed a group called Ashtray Heart. By around 1995, Ashtray Heart transformed into Placebo.

For Placebos first release, the band enlisted the technical skills of Chicago-based producer Brad Wood, who also worked with Liz Phair, Sunny Day Real Estate, and Jesus Lizard. On the surface, Placebo, issued by Caroline Records in the United States, contained some more traditional rock and roll ingredients, like heavy-metal guitar riffs and lyrics that celebrated sex and drugs. However, as Mark Jenkins concluded in a review for the Washington Post, the effect of the bands self-titled album is not exactly routine. Indeed, such ironically titled songs as Teenage Angst and Hang on to Your IQ are engagingly askew. Molkos vocals are so ambiguously high-pitched, on I Know, he scales heights reminiscent of the Undertones Feargal Sharkey. Placebos

For the Record

Members include Steve Hewitt (born c. 1971 in the U.K.; joined band C 1997), drums; Brian Molko (born C 1973; son of Scottish and American parents), vocals; Stefan Olsdal (born C 1974 in Sweden), bass, guitar, keyboards; Robert Schulzberg (left group C 1997), drums.

Formed in London around 1995; released self-titled debut on Caroline Records, 1996; toured with the Sex Pistols, U2, and Weezer, 1996-1997; released Without You Im Nothing on Virgin Records, played cameo role in Velvet Goldmine and appeared on the film soundtrack, 1998.

Addresses: Home London, England. Record companyVirgin Records, 338 N. Foothill Rd., Beverly Hills, CA 90210. Management Riverman Management. Booking Creative Artists Agency (U.K.).

debut also spawned the bands first hit single, Nancy Boy, which peaked at number four on the British charts.

Soon after releasing their highly-anticipated, self-titled debut album, the group seemed well on their way to establishing a name for themselves, appearing on the covers of both New Musical Express and Melody Maker, two well-known British publications. Moreover, they opened for the legendary punk group the Sex Pistols, David Bowie, and U2 in Europe, as well as for the pop band Weezer during that bands American tour. A lot of people were there just to hear [Weezer play] Buddy Holly, Olsdal recalled of Placebos lukewarm welcome from Americanaudiences, as quoted by Doug Reece in Billboard. We were getting coined [having coins thrown at them by the audience], so we just punked it up and ended up winning over a lot of crowds. Spending most of 1996 through 1997 touring in Europe and abroad, Placebo was also invited to perform for Bowies fiftieth birthday celebration held at New Yorks Madison Square Garden. By the end of 1997, Placebo had gained a respectable audience in Europe, and their fan base continued to grow in the United States.

Before starting work on their follow-up and debut major-label release for Virgin Records, Placebo replaced Schultzberg with a new drummer, Steve Hewitt, and also enlisted producer Steve Osborne. The addition of Hewitt and Osborne to the team, Olsdal believed, helped the band achieve a new direction for Without You Im Nothing, released in November of 1998. Comparing the bands first album to Without You Im Nothing, Olsdal described the latteras more schizophrenic, according to Reece. The first album was a very sexual record, Molko further explained, packed full of youthful vigor and lust. The new album is introverted, more of a post-coital depression: the comedown. It deals with an ever-pervading heartbreak and loneliness that seems to be in the air. The morning after is usually more analytical than the night before, and its often more painful, as quoted iMusic.com. On this album, we wanted to go away from that classic rock sound toward a more modern sound, Olsdal added, as quoted by Reece. Its more textured with expensive toys. On the first album, we were using toy instruments.

The time between Placebo and the debuts follow-up allowed the band to explore other musical pursuits and renewed their focus and energy. Theres two years between the two albums, and theres been a hell of a lot of living going on during that time, admitted Molko to iMusic.com. In many ways it feels like a different band. This is our first album with Steve on drums, and the band dynamic has changed. It can seem a bit schizophrenic, but were just trying to take it as far as possible in each direction: stretch it, and aim for a wider scope. And although Molko wrote most of the lyrics for the tracks on Without You Im Nothing, all of the band members contributed to the musics sonic flow. The first album was pretty much written by Brian in his bedroom. This album has been a three-way collaboration, revealed Olsdal.

The albums first single, Pure Morning, introduced Without You Im Nothing in a big way, debuting on the British singles charts at number four. A song that sounded somewhat reminiscent of the Butthole Surfers hit Pepper, Pure Morning immediately took hold of modern rock radio in the United States as well. I personally feel this is one of the most compelling-sounding albums to come out of England since Radio-head, a Los Angeles radio station executive, KROQs Gene Sandbloom, commented to Reece. [Pure Morning] is very unique, very alternative, and just something that immediately stands out on the air. Likewise, the expansive concept video for the single earned positive feedback on cable television network MTV.

In addition to giving a nod of approval to Pure Morning, music critics such as Eddy provided favorable references to the albums other songs as well. Tracks like Every You Every Me and Scared of Girls gallop with exhilaration; The Crawl and My Sweet Prince prance into preening spaces of piano gloom, wrote Eddy. The disc winds down to the triumphantly downtrodden Burger Queen (which swipes its sad tune from Altered Images 1981 New Waveclassic, I Could Be Happy). Molkos hissy-fit voice cracks toward transcendence whenever he hitches its pitch up another fruity notch.

By coincidence, the release of Without You Im Nothing corresponded with the November/December release of the glam-rock-era, Mirimax film Velvet Goldmine, produced by Michael Stipe. The movie includes a cameo appearance by Placebo, for which the band performed a cover of Marc Bolans [formerly of the now disbanded T. Rex] 20th Century Boy. Placebos version of the song also appeared for the soundtrack. In the great tradition of T. Rexwhose 20th Century Boy they actually improved for the Velvet Goldmine soundtrackPlacebos hooks are no less muscular for their androgyny, commented Eddy. About Placebos role in Velvet Goldmine, Olsdal recalled to Reece, We got dressed up in these ridiculous glam clothes and a lot of makeup and strut around onstage. It was a bit like being on a video shoot.

Selected discography

Placebo, Caroline, 1996.

(With others) Velvet Goldmine, (soundtrack), 1998.

Without You Im Nothing, Virgin, 1998.

Sources

Periodicals

Alternative Press, August 1999, p. 42.

Billboard, October 10, 1998, pp. 14, 20.

Melody Maker, July 24, 1999, p. 4.

Rolling Stone, February 4, 1999, p. 61.

Washington Post, September 20, 1996.

Online

iMusic.com, http://www.imusic.com/showcase/modern/placebo.html(November 29, 1999).

Rolling Stone.com, http://www.rollingstone.tunes.com(December 7, 1999).

Laura Hightower

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placebo

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Placebo

Placebo

In medicine, especially in clinical trials conducted for medical research, a placebo is a substance used as a control in a double-blind test. Half of a group of test subjects are given a medicinal substance being investigated, while the other half is administered an inert material, like a sugar pill, made to look indistinguishable from the medicine. In the optimal double-blind test, neither the research staff nor the test patients know which is which until the study has been completed. By this process, psychological effects of the placebo are hopefully kept separate from the biological effects of the chemically active agent being tested.

The non-medical definition of the word placebo indicates the general phenomenon called the placebo effect. Any action, such as gift-giving, which is intended to soothe an agitated person without directly solving any problem is referred to as a placebo. Indeed, the word placebo is derived from the Latin for I will please. As far back as the sixteenth century, the writer Montaigne commented that a patients faith in a doctor had more bearing on the successful outcome of a therapy than any other factor.

There is accumulating evidence that the use of a placebo can have a beneficial effect. This may be due to the release into the bodys circulation of of compounds called endorphins by someone who takes a placebo, believing that they are receiving a real medicine. Endorphins are analgesic (pain-reducing) chemical agents produced by the human brain. They serve the same purpose as morphine, a narcotic extracted from the poppy.

Even surgery can be used as a placebo, by cutting open a patient under anesthesia without actually operating. Control groups among angina sufferers have reported a decrease in chest pains after such dummy surgery, which indicates that angina may be at least partially psychosomatic. The problem with extreme placebos is the ethical issue of leaving any one patient untreated for the sake of being a control.

The use of a placebo is one of the important parts of a well-designed clinical trial. If the number of patients in the treatment and placebo groups is large enough, and if the trial is a double-blind design, then the effect of the drug being evaluated can be assessed with accuracy. Such trials are essential before a drug is introduced for general use.

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Placebo

PLACEBO

•••

The terms placebo and placebo effect are quite difficult to define. Most commonsense definitions contain serious inconsistencies. For example, one commonly hears placebo defined as an "inert remedy"; but if a placebo were totally inert, there would be no point in giving it.

In Latin, placebo means "I shall please," but the effects of a placebo can be either positive or negative (the term nocebo, roughly meaning "I shall harm," is sometimes used to designate negative effects). Adolf Grünbaum emphasized that whether or not a remedy is a placebo is always relative to some biomedical theory. A sugar pill is a placebo for a migraine only because the biomedical theory agreed upon by all discussants denies any pharmacologic efficacy of small amounts of oral glucose in altering the pain of vascular headache.

Some find it useful to locate the species "placebo" under the genus "nonspecific therapy," by which they mean a therapy that strengthens the general resistance of the organism to disease of many sorts (as opposed to a therapy that removes the specific cause of a single disease or class of diseases). But the latter term may be as hard to define precisely as placebo is. Moreover, there may be an unspoken assumption that nonspecific therapies are synonymous with "therapies that operate through psychological rather than biological mechanisms." But this is clearly false; some psychological therapies may be very specific for certain diseases according to established psychiatric theories, and some biological therapies, notably diet and exercise, seem to be good candidates for "nonspecific" status.

For purposes of ethical analysis, placebo effect may be defined generally as the change in a patient's condition that results from the symbolic aspects of the encounter with a healer or with a healing setting, and not from the pharmacological or physiological properties of any remedy used. The term symbolic alludes not only to the psychological processes that occur within the patient but also to the social and cultural belief systems that form a background to the patient's thoughts and feelings and that give meaning to the healing process. A placebo, then, is a remedy administered either for purposes of eliciting the placebo effect or as a control in an experimental situation. Virtually any modality, including surgery and psychotherapy, can function as a placebo; the term is not confined to pills, capsules, or injections.

The practical goal of defining placebo effect as precisely as possible is to distinguish the changes it produces in the patient's condition from changes produced by other causes. In treatment, the two factors likely to be confused with placebo effects are the pharmacological or physiological effects of the therapy employed and the natural history of the illness. For example, if a patient with gastritis visits a physician, who recommends antacids, and the patient improves, the relief could have come from the pharmacological properties of the antacids, the natural tendency of gastritis to heal over time, the soothing symbolic effects of the physician consultation, or some combination of the three. The two-group design in a controlled experimental trial ("active" treatment versus placebo) allows the investigator to distinguish pharmacological or physiological effects from the placebo effects and the natural history of the illness. It does not allow a distinction to be made between natural history and placebo effects.

It is also helpful to distinguish a pure placebo, thought to have no pharmacological potency under any circumstances whatever, from an impure placebo, which has pharmacological potency under some circumstances. Common examples of impure placebos are vitamins administered to patients who have no documented deficiency and antibiotics administered to patients who have viral illnesses (which do not respond to antibiotics). In today's medical practice, impure placebos are probably used much more commonly than pure placebos.

Scientific Controversies

A number of works published in 2001 showed the controversy surrounding the science of the placebo effect. A careful meta-analysis of 114 randomized controlled trials concluded that the placebo effect does not exist in that context, and changes previously attributed to the placebo effect resulted from either natural history or random variation (Hróbjartsson and Gøtzsche). Other scientists reported further evidence that placebo effects in pain are mediated by endorphin release in the brain (Amanzio et al.) and that alteration in dopamine release in response to placebo therapy for Parkinson's disease can be detected by positron emission tomographic imaging of the brain (de la Fuente-Fernández et al.). The results of a conference on "The Science of the Placebo" sponsored by the U.S. National Institutes of Health (NIH) were published (Guess et al.), and the NIH announced that research programs would for the first time be devoted specifically to studying the mechanisms and extent of placebo effects. Readers were thus led to various conclusions: that the placebo effect is a myth; that scientists understand better how it works; and that further research into its mechanisms will be fruitful. The majority view appears to be that the "myth" dismissal is premature and that more study is needed.

At the biochemical and cellular level, placebo effects may induce organ changes via the release of catecholamines, endorphins, or immunoactive cells; all three have been shown to be very sensitive to a patient's psychological or emotional state. At the social and psychological level, one must identify aspects of the setting or of the human interaction that cause the patient to perceive the situation as a healing one, thereby releasing whatever biochemically active substances might be involved. It appears safe to claim that a positive change in the patient's health status is most likely to occur when at least three things happen: the patient receives a satisfying explanation of the illness and treatment, the patient feels cared for and supported, and the patient feels an enhanced sense of mastery and control over symptoms.

During the 1990s and early 2000s, the ethics of placebo-controlled trials has been both challenged (Rothman and Michels) and defended (Miller and Brody). Besides the ethical questions concerning whether it is permissible to deprive research subjects of an effective standard treatment, some researchers have questioned how much scientific benefit is added by the use of a placebo control as opposed to an active-treatment control (Freedman, Weijer, and Glass). Systematic reviews have claimed that at least for selected conditions, such as depression, studies conducted without placebo controls might be scientifically suboptimal (Walsh et al.).

Ethical Issues

In the traditional use of placebos, a pharmacologically inert pill might be administered to a patient under circumstances that encourage the belief that a powerful drug is being given. Many patients—the average of one-third is often cited, though this conceals a wide variation among different settings—will experience some degree of positive response (White, Tursky, and Schwartz). This traditional use is ethically questionable because the patient is deceived. Therefore, an ethical analysis of placebo use might proceed with two questions. First, is deception necessary to produce the patient benefit promised by the placebo effect? Second, are there nondeceptive uses of placebos?

If one wishes to use placebo effects for the benefit of patients, one can simply work to enhance those aspects of the patient encounter that have been scientifically correlated with symptom improvement. One can show care, offer explanations, and enhance perceived mastery and control in many ways that require no deception whatever. Because, in the traditional use of placebos, the deception is justified by appeal to patients' benefit (Rawlinson), it is important to see that in almost all patient encounters, a nondeceptive alternative can produce the same result. Moreover, Sissela Bok argued, in her 1978 book, Lying, that the defender of the deception entailed in the traditional use of placebos makes two miscalculations: ignoring possible short-term harm(e.g., missing a diagnosis of serious disease because a placebo has temporarily relieved the patient's complaints) and failing to see how apparently trivial acts build up into collectively undesirable practices (e.g., overreliance on medication).

One may conclude that the traditional use of placebos in therapy can be justified only by very unusual circumstances (in which the use of a dummy pill is the only way to encourage the desired psychological state, for instance). By contrast, because reassuring patients and offering explanations and emotional support are part and parcel of good clinical care, one may argue that a physician has a positive ethical duty to try to enhance the placebo effect in every patient encounter (Connelly).

Counterarguments in defense of the traditional use focus on the claim that the deception is apparent rather than real (Spiro). It might be argued, for example, that if one gives the patient a placebo and says, "There, this will make you feel a lot better," one has not really lied. The increasing scientific interest in the placebo effect has triggered a resurgence of interest in administering placebos to patients, and some have claimed that placebo administration can be combined with respect for patients' rights and with appropriate informed consent (Brown). Perhaps the best reply to these counterarguments was put forth in a 1903 article by Richard C. Cabot: "A true impression, not certain words literally true," (Cabot, p. 345) is what the physician is obligated to promote in the patient. Most efforts at "informed consent" for placebo therapy still seem to rely on some element of equivocation, assuming that if the patient fully understood the pharmacologically inert nature of the remedy, no meaningful placebo effect would result.

Placebos may be employed in ways that do not entail deception and may therefore be fully licit. When placebos are used in controlled studies, it is generally possible to obtain a fully informed consent. It is also possible to use placebos in the therapy of individual patients in a way that avoids deception. One formal procedure for doing so has been termed the "N of 1 Trial," because it is basically a double-blind, controlled research trial performed on a single, informed subject (Guyatt et al.).

howard brody (1995)

revised by author

SEE ALSO: AIDS: Healthcare and Research Issues; Healing; Informed Consent; Pharmaceutics, Issues in Prescribing; Research Methodology; Research, Unethical

BIBLIOGRAPHY

Amanzio, Martina; Pollo, Antonella; Maggi, Guiliano; and Benedetti, Fabrizio. 2001. "Response Variability to Analgesics: A Role for Non-specific Activation of Endogenous Opioids." Pain 90(3): 205–215.

Bok, Sissela. 1978. Lying: Moral Choice in Public and Private Life. New York: Pantheon.

Brody, Howard. 1982. "The Lie That Heals: The Ethics of Giving Placebos." Annals of Internal Medicine 97(1): 112–118.

Brody, Howard. 2000. "The Placebo Response: Recent Research and Implications for Family Medicine." Journal of Family Practice 49(7): 649–654.

Brown, Walter A. 1998. "Harnessing the Placebo Effect." Hospital Practice 33(7): 107–116.

Cabot, Richard C. 1903. "The Use of Truth and Falsehood in Medicine: An Experimental Study." American Medicine 5(9): 344–349. Reprinted in Ethics in Medicine: Historical Perspectives and Contemporary Concerns, ed. Stanley J. Reiser, Arthur J. Dyck, and William J. Curran. Cambridge, MA: MIT Press, 1977.

Connelly, Robert J. 1991. "Nursing Responsibility for the Placebo Effect." Journal of Medicine and Philosophy 16(3): 325–341.

de la Fuente-Fernández, Raúl; Ruth, Thomas J.; Sossi, Vesna; et al. 2001. "Expectation and Dopamine Release: Mechanism of the Placebo Effect in Parkinson's Disease." Science 293(5532): 1164–1165.

Freedman, Benjamin; Weijer, Charles; and Glass, Kathleen Cranley. 1996. "Placebo Orthodoxy in Clinical Research, I: Empirical and Methodological Myths." Journal of Law, Medicine, and Ethics 24(3): 243–251.

Grünbaum, Adolf. 1989. "The Placebo Concept in Medicine and Psychiatry." In Non-specific Aspects of Treatment, ed. Michael Shepherd and Normal Sartorius. Bern, Switzerland: Hans Huber.

Guess, Harry A.; Kleinman, Arthur; Kusek, John W.; and Engel, Linda L., eds. 2001. The Science of the Placebo: Toward an Interdisciplinary Research Agenda. London: BMJ Books.

Guyatt, Gordon; Sackett, David; Taylor, D. Wayne; et al. 1986. "Determining Optimal Therapy: Randomized Trials in Individual Patients." New England Journal of Medicine 314(14): 889–892.

Hróbjartsson, Asbjørn, and Gøtzsche, Peter C. 2001. "Is the Placebo Powerless? An Analysis of Clinical Trials Comparing Placebo with No Treatment." New England Journal of Medicine 344(21): 1594–1602.

Miller, Franklin G., and Brody, Howard. 2002. "What Makes Placebo-Controlled Trials Unethical?" American Journal of Bioethics 2(2): 3–9.

Rawlinson, Mary C. 1985. "Truth-Telling and Paternalism in the Clinic: Philosophical Reflections on the Use of Placebos in Medical Practice." In Placebo: Theory, Research, and Mechanisms, ed. Leonard White, Bernard Tursky, and Gary E. Schwartz. New York: Guilford Press.

Rothman, Kenneth J., and Michels, Karin B. 1994. "The Continued Unethical Use of Placebo Controls." New England Journal of Medicine 331(6): 394–398.

Spiro, Howard M. 1986. Doctors, Patients, and Placebos. New Haven, CT: Yale University Press.

Walsh, B. Timothy; Seidman, Stuart N.; Sysko, Robyn; and Gould, Madelyn. 2002. "Placebo Response in Studies of Major Depression: Variable, Substantial, and Growing." Journal of the American Medical Association 287(14): 1840–1847.

White, Leonard; Tursky, Bernard; and Schwartz, Gary E., eds. 1985. Placebo: Theory, Research, and Mechanisms. New York: Guilford Press.

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Placebo

Placebo

In medicine, especially in clinical trials conducted for medical research, a placebo is a substance used as a control in a double-blind study . Half of a group of test subjects are given a medicinal substance being investigated, while the other half is administered an inert material, like a sugar pill, made to look indistinguishable from the medicine. In the optimal double-blind test, neither the research staff nor the test patients are allowed to know which is which until the study has been completed. By this process, psychological effects of the placebo are hopefully kept separate from the biological effects of the chemically active agent being tested.

The non-medical definition of the word placebo indicates the general phenomenon called the placebo effect. Any action, such as gift-giving, which is intended to soothe an agitated person without directly solving any problem is referred to as a placebo. As far back as the sixteenth century, the writer Montaigne commented that a patient's faith in a doctor had more bearing on the successful outcome of a therapy than any other factor.

The initial and often ongoing symptom being treated by a physician is pain , whether or not the cause of this pain is curable or even treatable. Sometimes treatment for an illness such as cancer leads to painful side effects, which must be tended. Only recent studies have begun to unlock the secrets of endorphins, analgesic or pain-reducing chemical agents produced by the human brain . They serve the same purpose as morphine , a narcotic first extracted from the poppy in the 1800s, and long used as an analgesic and anesthetic. There are still many questions as to what triggers an increase of endorphins in the body, how this contributes to the placebo effect, and how much endorphin production may be consciously controlled by a patient.

Other causes of pain are psychosomatic: stress-related, neurotic or phobic reactions with no detectable organic origin. Chronic discomforts describable as psychosomatic include allergies, ulcers, and hypertension . These conditions not only respond positively to placebos, they can also arise in a patient after taking a placebo, as negative aftereffects. Attempts to isolate a typical "placebo personality" have yet to succeed in predicting if any one person might be more susceptible to the placebo effect than another.

Even surgery can be used as a placebo, by cutting open a patient under anesthesia without actually operating. Control groups among angina sufferers have reported a decrease in chest pains after such "dummy" surgery, which indicates that angina may be at least partially psychosomatic. The problem with extreme placebos is the ethical issue of leaving any one patient untreated for the sake of being a control. The Tuskeegee syphilis experiment conducted in Alabama during the late 1930s is one example of an extreme clinical trial, during which penicillin was deliberately withheld from certain patients without their knowledge. While a few of these untreated patients survived, others died painful and preventable deaths.

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