Académique Documents
Professionnel Documents
Culture Documents
Placebo Effects:
Andrew G. Reece
Naropa University
April 2010
Running Head: INTEGRAL PLACEBOS 2
Abstract
This paper makes a broad survey of placebo effects in present and historical medical literature. Placebo
effects are considered from the perspective of Integral Psychology, specifically from the four-quadrant
model of holonic development. Additional sections cover the following topics: Arguments against the
validity of placebo effects, problems with identifying and measuring placebo effects, and ethical
This is a story about the power of stories. In a sense, storytelling is art of recounting of reality
from a particular perspective – from the way it seemed real to me, or you, or to an entire community.
Over the course of writing this particular tale, I have come to understand a paradoxical truth: that in
transmitting these stories there is a new reality, every bit as real, which is born with each new telling.
The stories of Mind, Body, Culture, and Environment, are not simply fanciful visions or subjective
opinions in a fictional frame of reference. Rather, they speak of what IS, and as their words come to
our ears, they actually serve to shape our view of the world, in and around us. I suppose I'm getting a
bit ahead of myself – telling the end before the beginning, as it were – but suffice for now to say that I
wasn't expecting to find out about this storyteller's secret when I set out to write this paper.
Originally, I had planned to write my thesis on the practice of long-distance healing, where a
healer exerts a beneficial effect on a patient from a remote location. Early on in my preliminary
research I quickly ran into the confounding problem of how to determine whether or not an observed
effect was actually brought about by the remote healer, or whether some other factor had contributed to
a patient's improvement. This soon led me to a deeper investigation of the placebo effect, a term used
to describe the curious phenomenon of the mind's ability to heal the body when it has been fooled into
thinking it has been given medical treatment, when in fact it has not. It didn't take long for me to
realize that there was a fascinating (and, not insignificantly, far-better documented) wealth of research
Placebo effects, along with their relationship to unusual phenomena like long-distance healing,
interest me because the greater part of my adult life has been spent in environments where the
inexplicable and esoteric are seen as commonplace. For the past ten years, I have travelled the world to
study with warriors, healers, mystics, and contemplatives, along my own path of self-inquiry and
pursuit of wisdom. I currently live on a small island in southern Thailand, in a community of yogis and
Running Head: INTEGRAL PLACEBOS 4
healers, where I am both a student and teacher. It has become something of a hobby of mine to look
into the scientific support for many of the theories and practices that I and my colleagues follow, many
of which originated in ancient spiritual traditions often thought to be incompatible with contemporary
scientific knowledge. In my research, I have uncovered a curious mix of authentic truth and regional
coloring; it has become my own personal aspiration to develop a spiritual practice and worldview that
To this aim, a comprehensive study of the placebo effect seemed invaluable, and indeed, it has
so proved itself. During the course of my research for this paper, I often fancied as though I could feel
my conscious mind rewiring connections and opening new possibilities, as I learned more about what
we know, as a collective, about the capacity of the mind (both individual and collective) to influence
and even govern our biological exteriors. As with most successful inquiries, I am left with more
questions than answers – but these new questions don't seem to demand their own responses; rather,
they sit formidably astride my accumulated worldview, dangling their legs near the top of my
perspective, continually presenting the same challenges: How much of what you are experiencing right
now is a product of mind? Where is the line between objective and subjective realities? Are they
I also consider my placebo research to be timely in another way. I have recently entered into a
new phase in my life, one in which I am attempting, as best I can, to strip bare the various assumptions
I have been carrying about myself, others, and the way the world works, and to start anew with an
open, honest, and authentic approach to rebuilding myself as an individual (as well as a part of a greater
whole). I'm not sure whether learning more about the power of placebos contributed to this new effort,
or whether the effort itself influenced my interest in them as a topic of research – I suspect the two
possibilities were and are engaged in a symbiotic relationship. Along with this new phase comes a
tremendous amount of doubt, or at least skepticism; in attempting to reformulate the way I experience
Running Head: INTEGRAL PLACEBOS 5
the world, I am trying to apply the sharpest discernment I have to evaluate those beliefs and
perspectives that make up my conscious mind. Many of the things I hold most sacred – my
understanding of yoga, my belief in a higher power, my own self-image – have come under a powerful
barrage of questions and new data (much of which I accumulated as a result of this research).
From what we know about the power of the physician as a therapeutic agent in his own right,
there is good reason to believe that much of the explanation for why a sugar pill can sometimes cure
disease lies not in the fact of the pill itself, but because the physician, whom the patient trusts, has
conferred the power of his authority into the placebo substance. The pill becomes a talisman, potent
for the ability to heal that it represents. It is a short leap from there to considerations of religious and
spiritual concern – and there the questions take on a wicked double edge: Does God provide us with the
placebos, conferred with Its Holy power? Or is God the placebo, an idea imbued with the confidence,
faith, and trust we place in our teachers? And even if the latter is the case, if placebos have genuine
power to deliver, then would it really matter, as long as we manage to invest our faith fully in Buddha,
in Tao, in Brahma? Is the disillusionment of the cosmos another way of saying that post-Enlightenment
culture found out it was being given a placebo? Or is our current reliance on rational-materialism a
placebo that wards off the existential fear of death and the unknown? These are questions with which I
currently wrestle.
At the same time, somewhere in the background, I can just barely feel a certain sense of deep
ease behind all this turmoil – perhaps this core equanimity is the one thing that will emerge as a stable
truth when the smoke clears. I rather suspect it will be so. In the meantime, though, I am intensely
grateful for this opportunity to make a comprehensive study of placebo effects, not only with respect to
my life, but also to my culture, social environment, and to the world at large.
Running Head: INTEGRAL PLACEBOS 6
The burgeoning discipline of placebo research tries to understand how seemingly useless
treatments, such as sugar pills and sham surgery, can yield tangible, therapeutic results.1 Medical
science refers to these as placebo effects, from the Latin “I will please” (Evans, 2004, p. 2). Although
for much of its early status as a medical phenomenon, placebo was thought to be related mainly to the
subjective phenomenon of analgesia (Beecher, 1955; Harrington, 1999; Levine, Gordon, & Fields,
1978), it is now understood that objective, physiological effects can be generated with placebo
treatments as well.2 In a recent meta-analysis, Mark (2009), for example, reported that placebo
recipients have demonstrated significant improvements across a wide range of pathology, including
bipolar mania, chronic fatigue syndrome, ulcerative colitis, Crohn's disease, depression, erectile
dysfunction, irritable bowel syndrome, migraine, osteoarthritis, pre-menstrual syndrome, and restless
leg syndrome. The problem arising today in placebo studies is therefore not one of acknowledgment,
but rather one of comprehension: even though most scientists now recognize that the placebo effect has
both psychological and physiological significance, still efforts to develop a more inclusive, integrated
medicine have been slow in forming. These efforts have been hampered largely by a lack of a coherent
framework within which to formulate a new vision. I propose that such a framework does exist, in the
ontological model laid out in theorist Ken Wilber's Integral Psychology. Integral Psychology offers a
cogent format for a more complete understanding of the significance of placebo studies, as well as for
This paper is divided into six parts. In Part One, I provide a clearer definition of Integral
1 Some placebo use today is true to this original notion of a placebo being a sugar pill or some otherwise completely inert
substance, however a distinction is now made between “pure placebos” and “impure placebos”. (Fässler, Gnädinger,
Rosemann, & Biller-Andorno, 2009, p. 3) The latter category indicates the use of active medicine not meant to treat the
ailment for which it is being prescribed, ie. giving antibiotics to treat a viral infection. Impure placebos are used more
frequently today than their purer counterparts. (Fassler et al., 2009; Hrobjartsson & Norup, 2003; Sherman & Hickner,
2007)
2 Analgesia is the medical term for pain relief.
Running Head: INTEGRAL PLACEBOS 7
Psychology and its composite parts. Part Two presents a literature review of relevant research which
supports my assertion that Integral Psychology is, in fact, a useful framework for understanding
placebo and the larger medical context. The review is divided into four sub-sections, according to
Integral theory's four-quadrant epistemological approach. (I'll elaborate on this more in the next
section). Part Three draws on the conclusions presented by each of these four perspectives, to
formulate a vision of a truly integrated medical model, based strongly on placebo research. In Part
Four, I briefly present some of the arguments put forth by skeptics, which attempt to discredit the
significance of the placebo effect. Part Five looks at a few of the most important issues facing placebo
studies today, and offers some speculation as to how future applications of the placebo effect might be
used in medicine. Finally, in Part Six I present a summary of findings, and point the reader to a handful
Before we can really get settled into our story, I first need to take a moment to introduce
Integral Psychology. Call it the flashlight I'll be pointing upward from under my chin as we all gather
'round the fire. The Integral system is its own vast network of stories, the full scope of which has
already taken up numerous volumes. As an introduction, however, the following should give us
Integral Psychology is a contemporary school of thought that regards personality and behavior
branch of Transpersonal Psychology, Integral Psychology was largely born out of the work of a single
theorist, American philosopher Ken Wilber (Visser, 2005). Wilber (2002) synthesized the spiritual
systems of the world's ancient wisdom traditions with 20th century developments in psychological
understanding, which he then used to model the full potential range of human development in an
Running Head: INTEGRAL PLACEBOS 8
elaborate spectrum of consciousness. The latest version of Wilber's Integral vision now extends
Integral theory asserts that human behavior can best be understood by employing a broad range
of analytical schema which Wilber (2006) refers to as the “AQAL” model (pronounced “AH-kwall”)
(p. 26). Wilber uses AQAL as shorthand for “all quadrants, all levels” (p. 26), indicating the model's
reliance on two primary modes of analysis – a four-quadrant epistemological grid of his own design,
and a scheme of gradated human maturation first outlined by researchers in the field of developmental
psychology. In the Integral framework, individual entities are considered as “holons” – units which are
wholes in themselves but also parts of greater wholes, such as in the relationship between atoms and
molecules, molecules and cells, and cells and organisms (Wilber, 2000, p. 7).3 Each holon, in order to
be fully understood, must be considered from at least four basic perspectives: its interior and exterior
characteristics, in conjunction with its individual and social qualities (Wilber, 2006). According to
interior, and collective-exterior – constitutes the minimum ways of looking at a holon in order to make
an informed statement about its overall condition (see Fig. 1). An individual born in Switzerland, for
example, has her own interior consciousness, as well as an individual body. In addition, her existence
is also undeniably affected by her being raised amidst Swiss culture (her collective-interior) and by the
social institutions (laws, government, means of transportation, media, etc.) which give her culture its
outer structure (her collective-exterior). It would be difficult, if not impossible, to relate to this
individual in her entirety, without first taking into account these four foundational perspectives.
Holons are also entities capable of maturation (Wilber, 2000). Drawing on the work of
developmental theorists including Piaget, Loevinger, Graves, Maslow, and Kegan, Wilber (2006)
described how this maturation unfolds in identifiable stages from lesser to greater complexity.
3 This is a term originally coined by Koestler (1967), to describe the organizational properties of organisms and life
systems in general.
Running Head: INTEGRAL PLACEBOS 9
This occurs over a broad range of developmental lines, among roughly two dozen distinct streams of
concern, ranging from cognitive to interpersonal to artistic and psychosexual (Wilber, 2000). An
emotional level (or vice-versa). The aggregate of a holon's various lines and each line's degree of
developmental maturity is referred to as the Integral “psychograph” (Wilber, 2006, p. 10, fig.1). In
addition, Integral Psychology employs various typologies (ie. Myers-Briggs, Gurdjieff's Enneagram),
as well as an awareness of the differing states of consciousness (waking, dreaming, deep sleep) to
This network of quadrants, levels, lines, types, and states makes up the bulk of Integral
Psychology's analytical model. Although the full scope of the Integral framework is exhaustively
Running Head: INTEGRAL PLACEBOS 10
comprehensive, for the purposes of this paper consideration will be mainly given to the AQAL model's
four-quadrant approach. The story told by the four quadrants is one of specialization in service to the
big picture, and in the often-fragmented world of medical research, that kind of approach can be very
useful. As such, I will present a review of placebo-related literature in the context of the four quadrant
model – I'll go through each quadrant, one-by-one, and show how unique, indispensable research is
being done which wouldn't be available from any of the other quadrants. To better set the stage for this
analysis, this next section will begin with a historical overview of placebo use in healing contexts
around the world, up to the present-day view of placebo effects and their role in modern medicine.
Voltaire famously noted that “the art of medicine consists of amusing the patient while nature
cures the disease” (Andrews, 1987, p. 72). From the perspective of modern medicine, this appears to
have been largely accurate for most historical healing systems. In a comprehensive survey of herbal
remedies used in ancient Chinese, Indian, Babylonian-Assyrian, Greek, and Roman medicine,
researchers Arthur and Elaine Shapiro (1999) concluded that out of the roughly 4,785 drugs and 16,842
prescriptions accounted for, “with only a few possible but unlikely speculative exceptions, all were
placebos” (p. 13). Certainly, the administration of placebos was commonplace by the early Industrial
Era. In an 1807 journal entry, US president Thomas Jefferson wrote of a prominent physician who
assured him that “he used more bread pills, drops of coloured water and powders of hickory ash than
all other medicines put together” (Evans, 2004, p. 3). Even Richard Cabot, perhaps the most famous
American physician of the early 20th century, confessed, “I was brought up, as I suppose every
physician is, to use placebos...for acting upon a patient's symptoms through his mind” (Harrington,
2009, p. 63). In nearly all cultures and eras which have some record of healing practices, from First
Nation shamans (Znamenski, 2007) to World War II front-line medics (Beecher, 1955) to modern-day
Running Head: INTEGRAL PLACEBOS 11
clinicians (Placebo: Healing the body, 2009), placebo treatments have been used as a matter of
common resource.
While the art of the placebo has existed throughout the course of recorded history, it is only
recently that we have begun to develop a more precise understanding of how it works, and for whom.
For instance, the oft-quoted statistic is that placebos are effective in about a third of any experimental
group. Beecher's (1955) seminal work on placebo effects is largely responsible for this statistic; since
its publication, actual rates of placebo efficacy have been shown to vary dramatically (Wall, 1992).
Placebo effects are nearly non-existent when treating some illnesses, such as cancer, and in other cases,
as in that of depression, placebos have been observed to be effective up to 90% of the time (Moerman
Benedetti (2009) notes that the term “placebo effect” is actually now something of a misnomer,
factors. Some of these factors may actually represent phenomena completely unrelated to the actual
treatment, which in one way or another may color the accuracy of a healing assessment. “Regression
to the mean”, for example (also referred to as “spontaneous remission”), describes the obvious (but
often overlooked) fact that many diseases or ailments simply get better on their own over time.
(Benedetti, 2009; Kirsch & Sapirstein, 1998) As many people seek out medical help either at or near
the height of their illness, any resulting treatment, whether active or placebo, may be aided by a natural
course of improvement. False reporting of improved or worsened conditions, either by the doctor or
the patient, can also skew assessment (Benedetti, 2009). In addition, co-treatment – the receipt of other
forms of therapy from a different source – often goes unreported and also contributes to a murky
These examples are among a wide range of factors potentially at play in the healing process. As
they do not relate specifically to the actual treatment in question, but yet still present the outward
Running Head: INTEGRAL PLACEBOS 12
conclusion of improved health or recovery, some physicians now prefer to distinguish between a
placebo effect and a placebo response (Benedetti, 2009; Kirsch & Sapirstein, 1998). A placebo
response is any observable improvement from a placebo treatment, after the effects of all outside
factors have been accounted for. The more general “placebo effect” represents the sum total of all
improvements that occur after a placebo is administered – this can include those elements mentioned
above, such as regression to the mean, passage of time, reporting bias, et cetera (Benedetti, 2009).
Even within the more narrow context of placebo response, however, there still remains a distinct
lack of consensus as to the actual nature of the placebo mechanism. Shapiro and Shapiro (1999) wrote,
“We are not even close to selecting the significant from the multitude of variables proposed as
underlying the placebo effect” (p. 29). Today, twelve years later, the exact extent to which
One reason for this lack of coherency in placebo research is due to a lack of collaboration
among different disciplines. As a result, disparate camps have arisen – some in biology, some in
psychology, some in pharmacology and even social anthropology – each of which is attempting to
evaluate the placebo effect in its own terms. In order to fully grasp the import of each groups' findings,
I believe it is first necessary to introduce a collaborative framework by which placebo researchers can
understand not only the significance of their own data, but also the synthetic wisdom available from a
inter-disciplinary view. I propose that the AQAL four-quadrant model of Integral Psychology is just
such a framework. The following section presents a review of relevant research literature intended to
illustrate more fully how the placebo effect is representative of distinct but mutually interdependent
factors, which line up nicely within the grid of the AQAL model.
As the dominant mode of inquiry in science remains one that uses empirical, observable data to
draw conclusions, the interior consciousness of the individual is often overlooked as unimportant, even
non-existent (Begley, 2007). But the idea that one's personal conviction – call it faith, belief,
assurance, or trust – is highly important to the healing process is an ancient one, with plentiful
examples (Brody, 1999; Harrington, 2009). In more modern times, take, for instance, the 1957 case of
Mr. Wright, as reported in Dylan Evans' Placebo (1994). Wright had been diagnosed with acute
lymphoma, with just weeks left to live, when he learned of a new experimental anti-cancer drug called
krebiozen and insisted that it be given to him. Within days of taking the krebiozen injection, Wright's
tumors shrank “from the size of oranges to the size of golf balls” (Evans, p. 12), and days later he was
released from the hospital, seemingly free of malignancy. When new findings revealed that krebiozen
was actually useless, his tumors returned. At that point, his doctor lied and said that the newspapers
were wrong, and that krebiozen was actually a powerful remedy. Wright's physician gave him a
placebo injection of saline (claiming it was krebiozen) and the tumors disappeared again. Months later,
when Wright learned that the American Medical Association had issued a formal statement indicating
the worthless status of the drug, his cancer returned immediately; Wright died just days after hearing
the news.
Other dramatic, medically confounding examples have been well-documented over the past
century. A case of congential ichthyosis, a disfiguring skin disease thought to be completely incurable,
disappeared from the arm of a 16 year-old boy after a doctor used an experimental form of hypnosis
(Mason, 1952). Harrington (2009) reported the story of a woman who refused treatment for life-
threatening injuries from a car accident, and instead completely healed her wounds after a night of
intense prayer. A French man completely debilitated by multiple sclerosis achieved a total recovery
(thought to be medically impossible) after a visit to the town of Lourdes, a holy site for Christians
(Harrington, 2009). Lourdes Medical Bureau chief Patrick Thellier later remarked with evident
Running Head: INTEGRAL PLACEBOS 14
surprise:
[The subject] suffered an organic infection of the multiple sclerosis type in a severe and
advanced stage of which the sudden cure during a pilgrimage to Lourdes corresponds with an
unusual and inexplicable fact to all the knowledge of science. It is impossible for medical
science to say anything more today. (Zenit International News Agency, 1999, Para. 9)
The firm conviction that a treatment will have a positive outcome can even override the effects
of a known toxic substance. Wolf (1950) reported giving two nauseous women (one of them pregnant)
ipecac, a strong emetic agent, while telling them that it would ease their discomfort. Both of them
reported immediate and lasting relief; normally, ipecac would have induced powerful vomiting within
moments of ingestion. Wolf concluded, “The above 'placebo' actions depended for their force on the
conviction of the patient that this or that effect would result” (p. 106).
Conversely, when patients believe they are receiving treatment that is harmful, even if the
substance is completely inert, negative effects can result (Barsky, Saintfort, Rogers, & Borus, 2002;
Hahn, 1997). This phenomenon is called the nocebo effect, from the Latin, “I shall harm” (Evans,
1994, p. 24). The case of Mr. Wright's recurring tumors (on hearing that his medicine didn't work)
could be considered an early anecdotal example of nocebo at play. Later, it was discovered that nocebo
could be produced by conditioning as well (Ader & Cohen, 1975; Amanzio, Corazzini, Vase, &
surgery, once thought to be a laughable concept, has produced significant results (Cobb, Thomas,
Dillard, Merendino, & Bruce, 1959; Johnson, 1994; Linde, Gadler, Kappenberger, & Rydén, 1999). A
recent set of studies employing sham arthroscopic knee surgery showed that placebo surgery can be just
as successful as actual surgery, calling into question the efficacy or ethical justification of subjecting
patients to such invasive surgery (Moseley, Wray, Kuykendall, Willis, & Landon, 1996; Moseley et al.,
Running Head: INTEGRAL PLACEBOS 15
2002).
What we broadly refer to as placebo extends even beyond the strict context of medical
treatment. Studies have shown that people who perceive their health as poor have much higher
mortality rates than people who believe they have excellent health, even when controlled for actual
health conditions (Idler & Kasl, 1991; Kaplan & Camacho, 1983). Crum and Langer (2007) conducted
a study of 84 hotel maids whose everyday work activity more than exceeded the US Surgeon General's
recommendations for daily exercise. Despite their rigorous workday, 66% of the maids reported not
exercising regularly, and 36.8% declared they did not exercise at all. Crum and Langer report:
Interestingly, the health of the room attendants reflected their perceived levels of exercise rather
than their actual levels: According to their initial physiological measures, the subjects were at
risk with respect to BP, BMI, percentage of body fat, and WHR—all important indicators of
health. These results suggest the possibility that at the onset of the study, the room attendants
were not receiving the full benefits of their exercise because they were not aware that they were
Langer's research team divided the maids into two groups, and gave only one of the groups an
extensive education on exactly how much exercise they were getting each day by performing their
daily work routine. These newly informed maids, along with the uninformed control group, were
instructed to continue about their work, without altering their activity. After four weeks' observation,
the uninformed group showed no significant signs of change, but the informed maids showed
significant improvements in every measure of health (weight, body fat, body-mass index, blood
pressure, and waist-hip ratio). These findings suggest that, at least in some cases, it is mental outlook
The interior perspective of not only the individual patient, but also the doctor, has some bearing
on the efficacy of medication, whether real or placebo. Gracely, Dubner, Deeter, and Wolskee (1985)
Running Head: INTEGRAL PLACEBOS 16
demonstrated this in a study of post-operative placebo analgesia for 60 patients recovering from
wisdom tooth surgery. Two groups of patients were informed that they would be receiving one of three
possible treatments: a powerful painkiller (fentanyl), a pain antagonist (naloxone), or a placebo. This
wasn't actually true though; doctors who administered the injections knew that one group (Group A)
would only receive either naloxone or placebo treatments (ie. no possibility of pain relief), while
subjects in the second group (Group B) could potentially receive the painkiller. Those who received
pain-enhancers and painkillers responded as expected. The people who received placebos, however,
showed surprisingly split results. Although the doctors were under strict orders not to relay their
expectations to the test subjects in any way, placebo recipients in Group A experienced far greater and
longer-lasting pain relief than did placebo recipients from Group B. Somehow, the doctors' own
internal states of knowing influenced patients' results. While the study authors speculated that the
doctors' foreknowledge could possibly have resulted in “subtle behaviors that influence patient
responsiveness,” their only clear conclusion was that “clinical analgesia depends not only on the
physiological action of the treatment administered, but also on the expectations of patient and
While these data strongly suggest that personal perspective is a powerful component of the
placebo effect, it should be acknowledged that the individual does not exist within a vacuum. Culture
and society play an important part in shaping our interior landscape of belief, conviction, and attitude,
and any attempt to understand the healing process without taking into account these factors would be
incomplete. This next section will examine how the various forms of community and collective
The most obvious collaboration in the context of medicine is that between the doctor and the
patient. The quality of the relationship that doctors form with patients has long been acknowledged as
Running Head: INTEGRAL PLACEBOS 17
having therapeutic implications (Benson & Epstein, 1975; Dixon, Sweeny, & Gray, 1999; Houston,
1938). Good bedside manner is an attribute appreciated even in the common wisdom of popular
culture; in the 1911 play, “The Doctor's Dilemma,” George Bernard Shaw describes the character Dr.
Bonnington as “cheering, reassuring, healing by the mere incompatibility of disease or anxiety with his
welcome presence. Even broken bones, it is said, have been known to unite at the sound of his voice”
From this perspective, many of the examples of placebo at work in the previous section,
ascribed to the strength of the individual's interior convictions, could just as easily be seen as having
originated from the shared relationships, exchanges, and meanings present in the medical environment.
Thomas (1987) showed that just by giving a firm, confident diagnosis, clinicians' positive interaction
with patients highly increased the likelihood of speedy recovery. Gryll and Katahn (1978) showed that
doctor-patient communication – specifically the implied meaning behind a doctor's choice of words,
and the confidence they impart to a patient – has a significant effect on placebo treatments. Patients
were given sugar pills before a dental injection, but doctors described the effects of the supposed
treatment differently, either expressing great enthusiasm for the efficacy of the treatment (“I've found
[this pill] to be very effective”), or low expectations (“I personally have not found [this pill] to be very
effective”) (p. 256). Patients who were given the enthusiastic explanation not only experienced less
actual pain, but reduced fear and anxiety related to the dental procedure as well. Gryll and Katahn
conclude, “These data argue rather strongly for paying close attention to what information patients are
given about the effects of drugs....either a warm dentist or a warm dental technician can potentiate
Beyond the immediate context of doctor-patient relationship, the wider cultural imprintings of
meaning, symbolism, and value, all have been shown to play a significant part in determining the
strength of placebos. Many studies have been done, for example, on the importance of pill color. Pink,
Running Head: INTEGRAL PLACEBOS 18
red, and orange pills have been shown to work best as stimulants; blue and purple pills work better as
sedatives and antidepressants (Blackwell, Bloomfield, & Buncher, 1972; de Craen, de Vries, Kleijnen,
1996; Schapira, McClelland, Griffiths, & Newell, 1970). The only known exception to the blue pill
rule is found among Italian men; Benedetti hypothesizes that this is because the Italian national soccer
team, a source of great pride and passion for many Italian men, is blue (Abumrad & Krulwich, 2007).
(Italian women responded much the same as the rest of the world.) The cultural and emotional
relationships people have to color are clearly strong enough to determine even the effectiveness of
pharmaceutical drugs.
The vehicle and route of administration makes a difference as well, based on cultural notions of
effectiveness. Hussain and Ahad (1970) noticed that sedatives in capsule form worked better than the
same dosage in pill form – in a time when capsules were a relatively new product and seen as an
advancement in technology. Placebo injections have been shown to work better than placebo pills for
blood pressure, headaches, and post-operative pain. (de Craen, Tijssen, de Gans, & Kleijnen, 2000;
Gracely, Dubner, & McGrath, 1979; Grenfell, Briggs, & Holland, 1961) Branthwaite and Cooper
(1981) even demonstrated that flashy, impressive packaging improves the power of placebos (as well as
actual medicine). Our cultural preferences for flash, color, and high technology have been shown to
Our perceptions of quantity, in addition to quality, also affect our experiences with placebo
medication. In the perspective of mainstream medicine, greater quantity of medicine almost always
means stronger effects. 100mg of medicine versus 50mg of medicine is expected to have a stronger
effect. Oddly enough, this holds for placebo treatments as well. Moerman (1983) and de Craen,
Kaptchuk, Tijssen, and Kleijnen (1999) both showed that subjects who received twice the quantity of
placebo medication (four pills instead of two) reported stronger healing reactions. Despite the seeming
obviousness of this relationship, between quantity and strength, it still must be recognized that this is
Running Head: INTEGRAL PLACEBOS 19
also an artifact of our cultural assumptions about medicine. By way of contrast, the alternative medical
paradigm of homeopathy considers smaller quantities of medicine to be more potent. I think it would
be interesting to see if someone who believed in homeopathy would have an opposite experience in a
Alongside these myriad curiosities, the wider convictions held by our collective belief system
about science and its ability to name and understand our world can have an impact on placebo and
healing as well. Brody (1999) remarks, “It is typical of the Western post-Enlightenment culture at a
certain time in history to believe that science can exercise power over the natural world and that it does
so in part by naming and categorizing natural phenomena” (p. 82). This acknowledgment, of our
reliance on the scientist's hold over nature, is not dissimilar to Harrington's (2009) description of the
pre-Enlightenment role of religion in exorcism: “The role of the priest was precisely delineated...he
must function as a sort of spiritual physician-cum-surgeon, first confirming the presence of the
demonic, then using his spiritual authority to expunge it” (p. 37).
Indeed, the power of physicians to heal, simply by virtue of their medical authority, is alive and
well in the minds of many people today. Take, for example, the recent study done on sufferers of
irritable bowel syndrome at Massachusetts General Hospital (Kaptchuk et al., 2008). There were three
arms of the trial: the control group, which consisted of patients under observation, but who were not
receiving any special care or treatment; a placebo treatment group, which received sham acupuncture
twice per week; and a placebo-plus-care group. Members of the third group followed the same sham
acupuncture regimen, but also received a full 45-minute consultation with their doctor, who encouraged
them to share what they felt their disease meant, and what sort of story they had to tell about it. After
three weeks, 44% of subjects who were given placebo treatment only showed marked signs of
placebo efficacy.4 Subjects in the placebo-plus-care group, however, showed an overall improvement
rate of 62%, a result that ranks as “comparable with the responder rate in clinical trials of drugs
currently used in the treatment of irritable bowel syndrome” (p.6). This indication, that quality time
spent between doctor and patient can, in some cases, successfully treat disease as well as an established
course of medication, seems laden with significance in a healthcare system where doctors are pressured
to limit face-to-face interactions with patients to seven minutes or less (Salgo, 2006).
Clearly, then, the cultural background which frames our encounters with medicine is another
distinctly powerful element at play here. In a sense, the placebo effect has spawned a greater
understanding of not only the mind's own hidden powers of healing, but also insight into the way that
medicine itself, once thought of as a model for objective, irrefutable scientific process, is in fact highly
susceptible to culturally-dependent values and meaning. This is not to say, of course, that the value of
medicine is completely determined by subjective impressions – even in the case of placebo treatments,
studies have demonstrated a clear neuro-physiological basis for this remarkable mechanism. The next
section will address how placebo effects happen in the quadrant of the individual-exterior – the human
body.
Just as personal and cultural history is responsible for the belief or mental attitude of the
placebo responder, there are also corresponding effects that occur in the physical body that serve as
testament to the power of individual belief and expectation. This information is relatively new, and still
forthcoming; up until the late 1970s, the prevailing view was that the placebo effect (if it existed at all)
took place largely in the subjective sphere, and that the physiology of the individual remained
unaffected, even if one's conviction in the power of a treatment made it seem to work. Today, we know
4The often-observed improvement that occurs in a small percentage of trial participants simply by virtue of their subjective
impressions related to being part of a trial is known as the Hawthorne Effect, and is another variable that is considered in the
effect vs. response debate in placebo studies (Parsons, 1974).
Running Head: INTEGRAL PLACEBOS 21
that this is not entirely accurate – it has been well-established that thought both expresses and
determines neurological activity. Science journalist Jonah Lehrer writes, “There is nothing inherently
mysterious about a psychological thought impacting the activity of neurons. That's what thoughts do”
(2008, Para. 3). Particularly in the fields of immunology and pain research, scientists have
demonstrated numerous times that there are undeniably placebo effects happening in the body as well
as the mind. From what we know today, there are two primary ways we can consider the placebo effect
at work in the physical body (the individual-exterior quadrant): first, as an effect born of behavioral
Ader and Cohen's (1975) experiment with rats and immunosuppresants was the first to show
that physiological placebo (or, in this case, nocebo) responses could be elicited through conditioning.
By giving rats sugar water laced with cyclophosphamide, Ader conditioned their bodies' immune
systems to be negatively affected upon the biological stimulus of the ingestion of sugar water. Even
after the chemical itself was removed from the water, rats with prior conditioning continued to have
weaker immune systems than others newly introduced to the sugar water. This proved to be a twist on
classic conditioning studies, as no overt psychological mechanisms were used in the conditioning
process, rather the rats' bodies themselves became conditioned without any conscious efforts on the
parts of the rats themselves. Numerous studies since then have verified this conditioning potential in
both animals and humans (Amanzio & Benedetti, 1999; Buske-Kirschbaum et al., 1992; Goebel et al.,
2002).
volunteers to painful electric shocks (kellyneill, 2009). He then administered an inert saline injection,
but told subjects it was a powerful painkiller. On the next round of shocks, the current was reduced by
60% (check stat) without subjects' knowledge. Subjects accordingly registered lower pain responses,
all the while believing that this was because the painkiller was working, and not because the strength of
Running Head: INTEGRAL PLACEBOS 22
the shock had been lowered. On the next round, the electrical current was turned back up to its original
power, and yet subjects continued to report lower levels of pain. Benedetti used this experiment to
In addition to the conditioned response evident in some placebo mechanisms, the mind's
Levine et al. (1978) demonstrated that pain relief from placebos could be disrupted by administering
naloxone, an opiod5 antagonist. This finding was the first to strongly suggest a neurological
mechanism at work – if placebo relief could be blocked by a neurochemical substance, then placebo
effects must at least in part be taking place in the brain. Although the initial experiment design had
several possible weaknesses, it has since been replicated with better controls in place, with the same
results (Benedetti, 1996; Grevert et al., 1983; Levine & Gordon, 1984).
Further research has turned up extensive evidence for placebo effects as acting along opiod-
receptive neural pathways (Amanzio & Benedetti, 1999; Petrovic, Kalso, Petersson, & Ingvar, 2002),
as well as a variety of non-opiod networks (Benedetti, 1996; (Fabrizio Benedetti et al., 1995); Brody,
1999; de la Fuente-Fernandez, 2001). These data indicate that placebo effects work along a diverse
array of neurological and physiological pathways, even beyond the confines of the brain and into the
vast neurological network of the body entire. Moyers (as cited in Brody, 1999) acknowledged this in
concluding that “the mind is part of a communication network throughout the brain and body” (p. 85).
Brody's (1999) comments regarding the ubiquity of peptide receptors6 further elucidate this point:
If identical peptide molecules are found to be active in the brain, the intestine, and the immune
system, and cells in all three tissues have receptors for the same peptide, then it seems quite
arbitrary to insist that a process goes on in the brain which is qualitatively different from
It has been further speculated that by mapping these specific pathways, it may be possible to
glean some insight via neurophysiology into the major psychological mechanisms responsible for
placebo efficacy in the subjective realm. Brody (1999) notes that peptide receptors are clustered most
heavily in the parts of the brain linked to generating emotion, and are least present in the cerebral
cortex (the center primarily associated with cognition), suggesting that “the placebo response is
principally linked to the patient's emotional reaction to a healing encounter and that it effectively
bypasses the patient's cognitive processes” (p. 86). Wager et al. (2004) and Lehrer (2008), on the other
hand, have observed placebo effects which seem to diminish activity in the emotional areas of the
brain, and increase it in cognitive areas. This issue remains a source of dispute, and one in which
Most recently, focus on placebo neurophysiology has shifted to phenomena observed in the
spinal cord. Matre (2006) and Goffaux, Redmond, Rainville, and Marchand (2007) both presented
evidence suggestive of spinal pain processing modulation during placebo analgesic effects. Eippert,
Finsterbusch, Bingel, and Buchel (2009) recently demonstrated via fMRI conclusive data showing that
placebo effects, at least in the realm of analgesia, occur first in the spinal cord's processing of pain
These data suggest a robust and highly inclusive framework for placebo activity in neurological
corridors. Over the past 30 years, research has demonstrated that a) subjective belief that a placebo
remedy is effective stimulates clear neurological effects, b) these effects are not limited to a single
response network (ie. pain relief, immune function, or mood regulation), and c) placebo activity is seen
not only in the brain, but extensive to the entire central nervous system (both brain and spinal cord). In
addition, certain researchers have made initial forays into the possibility that physiological data on
placebos may, in time, be able to actually inform us regarding the way placebos work in the subjective,
psychological domain, and not simply the other way around. (Brody, 1999; Wager et al., 2004) The
Running Head: INTEGRAL PLACEBOS 24
physical realm of the individual-interior quadrant has contributed valuable information to our overall
understanding of the mind-body relationship. The final piece to consider in this four-quadrant analysis
is related to the physical realm on a macroscopic level – the collective-exterior. This next section
examines how the material components of societal systems – namely, technological and economic
The collective-exterior quadrant deals exclusively with a society's exterior makeup, including
technological, economic, political, and institutional means. The growth of modern medicine has been
largely dependent on advances in this quadrant. A hospital can treat more patients with a wider range
of illness than a local physician, or an apothecary, ever could have. Ambulances and helicopters can
transport sick individuals to medical care with greater haste, and the laws of air and ground traffic
make special allowances for them to do so. Specific to our story, the many advances and discoveries
made in the neuro-physiological arena of placebo research have been entirely dependent on the level of
development of the systems in this quadrant. We can only know as much as we have the ability to
observe. In addition, the behavioral framework under which scientists conduct their experimentation
also plays a factor in determining the degree of accuracy and clarity of testing results. In this section
we will examine how the development and refinement of experimental methodology has affected our
understanding of placebo, as well as how brain imaging technology has improved our ability to
observe, on a minute level, the ways in which placebos transform the physical body.
Randomized Blindness
development and standardization of the double-blind clinical trial (Harrington, 2009; Shapiro &
Shapiro, 1999). For a trial to qualify as double-blind, neither the subject nor the administering
physician can have foreknowledge of whether the treatment being given is a placebo or an active
Running Head: INTEGRAL PLACEBOS 25
treatment. The double-blind method ensures both that testers will not be able to betray their knowledge
of the treatment contents (which, in doing so, could potentially influence the subject's perception), and
that patients are not primed to have a certain quality of experience. Results, therefore, are far more
Researchers also narrow down the range of possible explanations for trial outcomes by
randomizing, as best as possible, the demographic and medical backgrounds of trial participants. For
example, let's say a trial for hypertension medication is conducted with the only requirement being that
trial participants have high blood pressure. The trial results seem to indicate that the drug was effective
in lowering blood pressure, but then it is noticed that, for whatever reason, all the trial participants just
happened to be under 45 years of age, and a large number of them were Asian. This means that all we
can really say about the drug is that it seems to work for an under-45 population, and quite possibly the
results may be significant only for people of Asian ethnicity. Both the selection process as well as the
properly randomized selection process is the best way to ensure that a representative sampling across as
many factors as possible will be present during the trial. Randomization procedures combined with
double-blind testing have been combined in the randomized clinical trial (RCT), commonly considered
the gold standard for medical research today. As placebo effects are observable in all but the most
dramatic forms of illness or injury (cancer and broken bones, for example), they have taken a place of
primary importance in RCTs as the benchmarks against which new treatments are tested.
Observational Technology
The available technology of a given era quite literally determines how well any medical
the early years of placebo research, researchers' ability to see into the inner workings of the brain was
7 See Gracely, Dubner, Deeter, and Wolskee (1985) for an example of revealed bias when trials only include subject
single-blinding.
Running Head: INTEGRAL PLACEBOS 26
extremely limited, as digital imaging techniques were still decades away from being invented. As a
result, the placebo effect was thought to be primarily a subjective phenomenon, limited entirely to the
subject's perception, and divorced from the actual physiological goings-on of the body. (Beecher, 1955)
Later, the emergence of physiological and neurological imaging techniques such as positron emission
tomography (PET) and functional magnetic resonance imaging (fMRI) led to a greater understanding
of exactly what a placebo effect looked like, as now scientists could see its effects both in the body as
well as observe its impact on the psychology of their subjects (Kong et al., 2006; Lieberman et al.,
2004; Petrovic et al., 2002; Wager et al., 2004).8 While Benedetti (2009) acknowledges that “modern
brain imaging techniques have been fundamental in the understanding of placebo analgesia” (p. 80),
still for the most part, the importance of this quadrant is often overlooked, even taken for granted, when
assessing the varied factors at play in our understanding of the placebo effect, and of medicine as a
whole. Indeed, the social framework and technology base under which we operate is of foundational
importance to our clear perception of mind-body interactions and their medical implications.
Although each of the four quadrants is able to inform us in their own unique capacity, I would
contend that only in examining the placebo phenomenon from an all-quadrant view can we most fully
comprehend its significance to the fields of medicine and health. Particularly from the arena of placebo
research, a growing number of physicians and researchers are calling for a more inclusive model of
medical treatment. Based on the results and implications of placebo research as outlined in this
chapter, in the following chapter I will argue for the necessity of transitioning towards a truly integrated
medical model.
8 In layman's terms, PET scans work by injecting a short-lived radioactive substance into the bloodstream, which
eventually gets to the brain. The scanner picks up on the glow given off from the radioactive decay, and makes a picture
with it. FMRI, on the other hand, measures the change of blood flow to different areas of the brain and spinal cord.
Where there's blood flow, there's increased neural activity, so an image of these changes gives a fair idea of what's
happening in the brain at a given moment.
Running Head: INTEGRAL PLACEBOS 27
Integral theory insists that it is not just a good idea to look at a thing from its four fundamental
perspectives, but rather it is imperative that we do so. One simply cannot claim to speak authoritatively
on a subject without a good sense for the reality – the story – of each of its four quadrants. Wilber
(2000) writes, “In our quest for an integral holism...we want to honor all four quadrants, and not
merely privilege one of them in a reductionism blatant or subtle” (p. 72). This truth is clearly reflected
here in the placebo literature – the findings of neurological activity in the brain and spinal cord are
meaningless without knowing about the subjective perceptions that trigger these neural pathways.
Looking at placebo from a purely subjective individual standpoint doesn't really take into account the
way that cultural background can shape our understandings and conceptions, which in turn make us
more or less susceptible to placebo effects under certain circumstances. The degree to which our
collective technology base has grown over time is intimately linked with our ability to see the placebo
for what it is when experimenting in the individual quadrants. And so on and on it goes – the
livelihood of placebo research in any one quadrant is dependent on all the others, and to do anything
This is an important truth that applies far beyond the field of placebo research. After all, what
do we know about how well medicine works, other than from comparisons to placebo effects? In the
United States, the current standard set by the Food and Drug Administration (FDA) is that any new
drug must have performed better than placebo in two separate authenticated clinical trials in order to be
considered for distribution to the public (Silberman, 2009). But seeing placebo effects through the lens
of the four quadrants, it becomes obvious that there isn't just one effect at play, but many.
Pharmaceutical companies, in order to come up with viable products, are essentially competing against
the healing power of everything involved in the process besides actual pharmacological substances,
from the personalities of the individuals involved in clinical trials, to the cultural biases implicit in
Running Head: INTEGRAL PLACEBOS 28
participants' expectations, to the degree to which available technology can distinguish between real and
artificial results.
Two important results come out of the way that this system currently operates. First, the more
that is known about the placebo effect, the more the exact importance and effectiveness (or, in some
cases, ineffectiveness) of active medical treatments can be measured and understood. At the same time,
the more we find out about what makes a placebo powerful, the more we find out about a core set of
phenomena that are present to some degree in every treatment of every medical patient. The exact
degree to which placebo effects are present in drug treatments varies considerably, but some studies are
starting to indicate that the percentage is much higher than anyone had previously thought. All of
which is to say that as physicians become more knowledgeable about placebos, they become better,
more honest, and more efficient healers. In this section, I will lay out an argument for why it is
important, even vital, for the future of medicine, to adopt an integral, all-quadrant, placebo-inclusive
approach.
The placebo effect has basically taken on the position of an adversary to medical researchers
and pharmaceutical companies. This attitude, however, is based on old, outdated thinking which
assumed that placebos were acting purely at a subjective level, and that they could not be responsible
for any genuine physiological effects in the body. As reviewed in Part Two, there is now extensive
evidence for the fact that some aspects of the placebo effect are real, that they stimulate definite
neurological activity and can generate observable shifts in the physical body.
Perhaps more significant is recent evidence that suggests some aspects of placebo effects,
specifically related to the degree of caring present in the physician's attitude towards the patient, are as
important and successful for treating some disease as even the best pharmaceutical solutions. Recall
Kaptchuk et al. (2008), which strongly suggested that bedside manner, an interpersonal placebo of
Running Head: INTEGRAL PLACEBOS 29
sorts, is in itself a powerful healing treatment. Compared to Sherman and Hickner's (2007) findings
that only 51% of doctors surveyed believed that the doctor-patient relationship is of psychological and
physiological help to the patient, this disparity suggests an enormous potential healing resource in
methods and treatments which are currently relegated by the medical community to the taboo category
of “mere placebo”.
Furthermore, new evidence has emerged in recent years that indicates that, in several high-
profile situations, these supposedly “mere” placebo effects have been mistaken (or purposely
mislabeled) as effects of active medication. Specifically, Kirsch and Sapirstein (1998) determined that
popular antidepressants actually had never performed much better than placebo in clinical trials, yet
were made available on the market anyway due to a convenient mixture of technicalities and half
truths. Kirsch and Saperstein used the US Freedom of Information Act to request all of the clinical
trials that pharmaceutical companies had submitted to the FDA for the six most widely-used
antidepressants from 1987 to 1999. The resulting meta-analysis revealed a mean drug-placebo
improvement difference far below clinical significance (1.8 points versus the required 3.0 points to
qualify as clinically significant on the Hamilton Rating Scale of Depression). Said in another way,
none of the antidepressants on the market during this period had demonstrated improvements at a level
which would be considered meaningful in a real-world setting, but were allowed to go out for public
consumption due to their statistical (not clinical) victory over placebo treatment. In another article,
Kirsch (2005) noted that antidepressant drug responses only were able to attribute about 25% of their
effectiveness to the actual drug under trial, with nearly 50% of the response being related to some
Data like these cast a curious light on the role of regulatory bodies in medicine, such as the FDA
– why would these organizations allow a drug to be purported as useful or effective if the actual
evidence failed to support such a claim? In fact, internal memos from the FDA show that this is a
Running Head: INTEGRAL PLACEBOS 30
matter of some debate, even within the organization, as is evidenced by this 1998 communication from
Paul Leber, then director of the FDA Division of Neuropharmacological Drug Products, regarding
I believe it is useful for the prescriber, patient, and 3rd-party payer to know...that citaprolam's
antidepressant effects were not detected in every controlled clinical trial intended to
demonstrate those effects. I am aware that clinical studies often fail to document the efficacy of
effective drugs, but I doubt that the public, or even the majority of the medical community, is
aware of this fact....The Office Director is inclined toward the view that the provision of such
information is of no practical value to either the patient or prescriber. I disagree... (Leber, 1998)
However commendable the perspective laid out in this memo, the FDA practice of protecting
questionable drugs continues. When the Washington Post ran a 2004 story on the apparent lack of
evidence for antidepressant drugs being effective for children, it reported the following:
The Food and Drug Administration has repeatedly urged antidepressant manufacturers not to
disclose to physicians and the public that some clinical trials of the medications in children
found the drugs were no better than sugar pills, according to documents and testimony released
Regulators suppressed the negative information on the grounds that it might scare
families and physicians away from the drugs, according to testimony by drug company
executives. (Vedantam)
This effort to maintain the public's belief in medicine, despite failed trial results, implies that the
FDA understood that the belief itself was more important than whether or not the drugs actually
worked. This is tantamount to acknowledging that it is the power of belief – or, said another way, the
power of placebo – more than the power of any single medicine, that is at the heart of the medical
system.
Running Head: INTEGRAL PLACEBOS 31
If you can create a more effective healing practice based on the manipulation of meaning, then
you're going to heal more people. Is it some sort of failure if it isn't due to a pill? The
With the stark irony of the FDA's position in mind, along with substantial evidence showing
that not only are placebos important and useful, but that doctors believe in them and use them in their
clinical practice, it seems to be an eminently reasonable suggestion that placebos be embraced, rather
In order to effectively integrate the power of the placebo into modern medicine, first the concept
of the placebo effect must be considered from an Integral, all-quadrant standpoint. Placebos, as we
have seen, are far more than simple variations on Jefferson's “bread pills [and] drops of colored water”
(Evans, 2004, p. 3) Rather, the placebo effect stretches to include elements of personal conviction,
belief systems, and personality (the placebos of the individual-interior), as well as the ways culture and
society shape and support those systems (the effect of the collective-interior). The actual pill given to
the patient, be it active or inert, is in large part simply a condensed symbol of meaning related to the
much bigger quadrants of the subjective interior from which it gains its authority. The physician, too,
becomes a representative of the intersection of the quadrants of medicine and healing, one who has
some understanding and ability to manipulate the truth of each individual domain. Unpacking the
placebo in this way reveals that a fully integrated understanding of placebo effects leads to an integral
There are some signs that seem to indicate physicians are already looking for more holistic
ways to approach their trade, ways that include the fullness of the four quadrants' perspectives.
Running Head: INTEGRAL PLACEBOS 32
Thomas' (1987) clinical research showed a demonstrable, significant improvement in patients who had
positive, caring physicians. Kaptchuk and Jacobson (personal communication, December 10, 2009) are
currently making an anthropological assessment of their 2008 work with IBS patients, to look for fresh
insights on their already-strong data regarding the importance of doctor-patient relationships. Brody
(1999) focused on the importance of qualitative and ethnographic research methods to understand
disease. In Sherman and Hickner (2007), 74% of Chicago physicians interviewed said they felt that
emotional health was an important factor in not only psychological health but physiological health as
well; 65% also felt social support systems were of psychological and physiological help to patients
recovering from illness. That medical physicians are stressing a need for social support groups,
emotional health, cultural understanding of disease and illness, and a caring bedside manner, seems
significant in a culture which has become conditioned to expect that a cure for everything exists in the
The Integral approach, however, would stress that it is equally as important to address the
objective sphere of medicine as well. No real success can be gained by a reversal of trends, to go from
the starkly objective landscape of physical medicine, over completely to the warm and caring world of
the emotional interior of doctor-patient relationships. Both objective and subjective must be considered
equally and appropriately in an integral model. The 2000 New York Times article, “The Placebo
Prescription,” articulates the proposed role of placebos in bridging this divide, wondering,
What if they started thinking of placebos as a way of bridging the gap between the magnificent
but sometimes cold efficiency of modern American medicine and the unproven but evidently
To accept the placebo effect openly as a viable part of medical treatment is to make the first
steps in establishing a truly integral medicine, one that goes beyond the borders of objective-exterior
priority which assumes medicine starts and ends within the perimeter of the physical body. In Part
Running Head: INTEGRAL PLACEBOS 33
Five, we will look at some of the current discussion surrounding just how this might eventually happen.
First, though, I would be remiss in this presentation if I were to ignore the storytellers on the other side,
so to speak – the objections of those who remain skeptical about the usefulness, and even the very
existence, of the placebo effect. Part Four gives voice to these objections, as well as to my own
Despite the overwhelming evidence now available to medical science, which points to the tenable
reality of placebo effects, there continues to be a small but persuasive minority which considers the
placebo effect to be grossly overstated in its importance, or, even not to exist at all. This section will
briefly outline the arguments against the placebo effect, as well as the evidence their proponents use to
One such argument stems from the valid assertion that the placebo effect isn't really an effect at
all, but many phenomena rolled into one. Many of these phenomena can be understood or explained by
other known issues – regression to the mean, reporting bias, outside factors at play, etc. (Benedetti,
2009). Other effects observed after placebo treatment, such as feelings of relief, are subjective and
cannot really be determined in a specific cause-effect relationship (palMD, 2009). After all these things
have been accounted for, placebo skeptics say at the very least it is important to acknowledge that any
actual placebo responses would constitute a small percentage of the overall pool of phenomena
Some even go so far as to say that placebo effects don't exist at all. Hrobjartsson and Gotzsche
(2001) conducted a meta-analysis of 114 clinical trials and found overall that results from groups which
received placebos were not significantly greater than those from no-treatment groups, with small
exceptions made for some subjective measures, such as pain relief. While this report served as a
Running Head: INTEGRAL PLACEBOS 34
rallying call for many placebo skeptics, significant criticisms were later leveled at its findings,
including the fact that overall findings combined results from trials for both objective and subjective
illnesses. Placebos tend not to work reliably on difficult physical conditions such as cancer or anemia,
so by including studies which focused on these illnesses in a meta-analysis along with more placebo-
prone ailments like asthma, skin rashes, and depression, it has been suggested that the authors' findings
should more properly be characterized as having demonstrated that placebos do work, but primarily for
Nunn (2009) argued instead against the existence of a placebo effect, on grounds of the many
failed attempts to define exactly what a placebo is. If, Nunn questions, placebo are inert substances,
then how can they have active effects? If they are treatments with non-specific effects, then how can
you observe the effects – wouldn't that then make the effects observed specific? The set of paradoxes
proposed by placebo definitions prompted Nunn to question its actual existence: “Nobody who came
and saw the placebo has conquered its definition....If something cannot be defined and does not make
sense no matter how it is viewed, it’s time to ask if it’s really there at all” (Nunn, p. 1015).
I personally have not been convinced by those who claim the placebo effect doesn't exist.
Hrobjartsson and Gotzsche's (2001) study seems to actually indicate the reality of placebo effects when
the data are carefully examined. I do agree that it is useful to be clear in differentiating known factors
which complicate trial findings (regression to the mean, reporting bias, etc.) from actual placebo
responses (if in fact they do exist), and to this end I think that to lump all apparent but non-specific
healing phenomena under a single category is somewhat misleading. This, however, is not to say that
in the final analysis, all of the healing effects observed over the course of a recovery period will be
explained away by concrete phenomena. I do think it is possible that an actual, yet-unidentified healing
mechanism does exist which relies heavily on the patient's subjective (conscious and subconscious)
relationship to the healer, the healing environment, and the treatment itself, and that some day we will
Running Head: INTEGRAL PLACEBOS 35
This will only be determined as our technological capacity to observe and analyze healing
processes continues to grow, much as our understanding of placebos now far surpasses the meager
knowledge available at the onset of their inclusion into standard medical practice, earlier in the 20th
century. For now, I think it's enough to acknowledge that there is a set of powerful, still poorly-
understood healing effects that can be induced through certain means, including simulated treatments,
strong doctor-patient relationships, and cultural attitudes towards medicine, and that this should be
In this next section I will look at the future potential of the placebo in its own right: how can the
power of the placebo be effectively harnessed by modern medicine, not simply, as one journalist put it,
“statistical noise competing with the active drug” (Silberman, 2009, para. 54), but as an effective and
openly-acknowledged treatment in its own right. In order to answer this question, we first need to look
Steve Silberman's article in the September 2009 issue of WIRED magazine, titled “Placebos Are
Getting More Effective, Drug Makers Are Desparate To Know Why”, addresses the increasing body of
research literature which suggests that the placebo effect is somehow getting stronger. Admittedly, it is
somewhat misleading to claim that placebo effects are actually growing; Bell's (2009) response to
Silberman notes that this statement is really “another way of saying that the difference between placebo
and the drug is getting smaller” (para. 9). That distinction having been made, the exact reasons for this
seeming increase are still unclear, although several theories exist why this may be happening.
The first and most obvious reason, writes Silberman (2009) is that drug companies have done
Running Head: INTEGRAL PLACEBOS 36
such an effective job at marketing their products, that consumer confidence translates into a higher
expectation among clinical trial participants that their treatment will be effective. The second possible
cause for higher placebo rates relates to the greater lengths which pharmaceutical companies need to go
in order to find trial participants who are “therapeutic virgins” – individuals who are not already taking
some form of medication (Silberman, 2009, para. 45). This search has led companies farther and
farther abroad, as more and more individuals in First World countries turn to medication as a long-term
solution for physical and psychological ailments. Doctors in remote regions who are paid to fill trial
rosters may end up including patients with milder symptoms (who would thus be more likely to
respond to placebos) than would normally be acceptable. And individuals in poorer regions with little
or no access to healthcare not only might have stronger hopes for improvement upon going into clinical
trials, but in addition the standard of healthcare in clinical trials is often far superior to that found in any
normal medical facility in impoverished areas; the high quality of in-trial care alone could explain a
Bell (2009) and Silberman (2009) both stressed that a major, although unverified, reason for the
seeming increase in placebo effects may be the continual improvement of study design and quality
control. Silberman pointed out ratings from clinical trial observers using standardized tests actually
varied significantly between different testing sites. This, wrote Silberman, “was like finding out that
the judges in a tight race each had a different idea about the placement of the finish line” (2009, para.
22). Bell cites Schulz, Chalmers, Hayes and Altman (1995), who demonstrated that studies of higher
methodological design significantly reduced errors and biases in estimates of treatment effects. Bell
writes, “So one reason why the placebo effect might be increasing is that studies are just more rigorous
these days” (2009, para. 12). Although speculative, this simple explanation for the placebo effect's
Whatever the actual reasons may be, drug makers of late have been beset with increasing
Running Head: INTEGRAL PLACEBOS 37
tendencies for both new and previously approved drugs to fail against placebo in clinical trials. Major
pharmaceutical companies, including Merck, Pfizer, and Eli Lily, have canceled trial research for new
drugs meant to treat a wide range of illnesses, including schizophrenia, Parkinson's disease, depression,
rheumatoid arthritis, and Crohn's disease, after they failed to outperform placebos (Myers, 2009;
Silberman, 2009). Even tried and true brands such as the antidepressant Prozac are now consistently
failing to beat placebos. Silberman (2009) writes, “Some products that have been on the market for
decades, like Prozac, are faltering in more recent follow-up tests....If these same drugs were vetted now,
the FDA might not approve some of them” (para. 8). From a four-quadrant standpoint, it would seem
that these curious and sometimes confusing data are problematic principally because of a lack of
attendance to the collective-exterior – the behavioral patterns and technological capabilities of the
medical discipline which determine in a very real way the degree to which any particular phenomenon
can be studied.
In addition to overall trends showing a rise in placebo effects across the board, new research
indicates that placebo rates differ based on the geographic region in which trials are conducted.
Arthritis patients in South America have been shown to have significantly higher placebo response
rates than in Eastern Europe, for example (Myers, 2009). Moerman (2000) found considerable cultural
variation in placebo efficacy rates, noting that placebos for ulcer disease in Brazil were less than 20%
as effective as the world average (7% vs. 36%), while rates in Germany were twice as high as the rest
of the world. Among hypertension studies, however, placebo recipients in Germany showed the least
improvement out of the entire international trial pool, and only “middling” results for anxiety
treatments (Moerman, 2000, p. 63). Although Moerman suspects these differences are due to cultural
attitudes towards different diseases, no concrete evidence has been found to support this hypothesis.
(Although as discussed in Part Two, extensive evidence exists to show that cultural influence in general
Running Head: INTEGRAL PLACEBOS 38
These data are poignant reminders of the importance of the collective-interior, a world of
cultures within cultures, where even one's allegiance to a sports team can effect the outcome of medical
treatment. The extent to which these factors play an influential role in placebo studies is still rather
poorly understood, and strongly calls for further research in the area of psychosocial influences on
medical treatment. Keeping in mind these unanswered questions about the nature of placebo effects, I
will now turn to the main issue concerning the future of placebos as medical resources: Knowing how
powerful an ally the placebo effect can be to conventional medical treatment, is there a way to employ
placebos as treatments in their own right, in a safe and ethical way? The second half of this section is
devoted toward identifying and understanding the different perspectives which are vocal in the ongoing
The success of placebos seems to rely on the patient believing that they are effective remedies.
This raises an important ethical issue in the ongoing debate over whether it is possible to use placebos
in clinical practice in a meaningful way; while most medical professionals acknowledge the reality of
the placebo effect, many have also expressed discomfort with the idea of deliberately deceiving
patients, even if there may be a fair chance that a placebo treatment will help. Nordenberg (2000)
render extralegal activist rulings, winegrowers to bottle `placebo' vintages, curators to display
such a world, all of us would be groping for truth in a hall of mirrors. (p. 5)
Much of this concern is grounded in the established standards of medical care that have been
developed by the global medical community over the past century. One modern version of the
Running Head: INTEGRAL PLACEBOS 39
Hippocratic Oath, for example, specifically requires that no treatment be carried out without a patient's
“valid informed consent” (US Army, para. 10), effectively eliminating the possibility of using placebos
covertly. The Helsinki Declaration, a medical code of ethics adopted by the World Medical Assembly
in 1964, affirms that “every patient...should be assured of the best proven diagnostic and therapeutic
method” (Vollman & Winau, 1996, p. 1449), which puts a placebo treatment in the challenging position
of being able to prove that it can be equally or more effective than a given pharmacological or surgical
treatment. This conflict, between the motivation to use whatever treatment may be necessary to effect
healing – including placebos – and the physician's desire to be in complete ethical integrity, on the
other, has led to paradoxical attitudes among doctors. In a 2003 survey of Danish physicians, for
example, 86% of all respondents reported having given patients placebos at least once within the last
year, but only 46% found the clinical use of placebos ethically acceptable (Hrobjartsson & Norup,
2003). The study's authors go on to specify that “of the respondents who found placebo treatments
unethical, 50% reported they still had prescribed them” (p. 160). Other surveys conducted in different
countries, including Israel, Switzerland, and the United States, report similarly contradictory
sentiments, revealing the reality of a medical community in deep conflict with itself over appropriate
placebo usage (Fässler et al., 2009; Nitzan & Lichtenberg, 2004; Sherman & Hickner, 2007).
More specific than the general debate over the use of placebos, another contentious issue arises
regarding the motivation behind a physician's administration of a placebo treatment. The American
Medical Association (2007), while allowing their conditional clinical use9, explicitly forbids issuing
9 The current position of the American Medical Association (AMA) on placebo use in clinical settings is one open but
flexible disclosure. The AMA Code of Ethics states: “Physicians may use placebos for diagnosis or treatment only if the
patient is informed of and agrees to its use” (AMA, 2007, para. 2). Some leeway is provided within this context, however,
as physicians are permitted to conceal the exact details of placebo use. The AMA guidelines continue:
A placebo may still be effective if the patient knows it will be used but cannot identify it and does not
know the precise timing of its use. A physician should enlist the patient’s cooperation by explaining that a better
understanding of the medical condition could be achieved by evaluating the effects of different medications,
including the placebo. The physician need neither identify the placebo nor seek specific consent before its
administration. In this way, the physician respects the patient’s autonomy and fosters a trusting relationship, while
the patient still may benefit from the placebo effect. (AMA, 2007, para. 2)
Running Head: INTEGRAL PLACEBOS 40
placebos “merely to mollify a difficult patient” (para. 3), although this seems to be a prohibition
directed at sham medication, as opposed to other “placebo-like effects” (para. 3) brought about by an
attentive bedside manner, which are, in fact, encouraged. Physicians around the world appear to
interpret placebo-usage guidelines in different ways, in many cases acting in outright defiance of the
spirit of such codes of conduct. For example, Sherman and Hickner's (2007) aforementioned survey of
practicing doctors in the Chicago area reported almost half of all respondents having knowingly given
patients placebo remedies. Only 11% of those who reported placebo use, however, prescribed placebos
“after all clinically indicated treatment possibilities were exhausted”, with another 6% having given
them with the intent “to control pain” (p. 8). The rest of the physicians who gave reasons for their use
of placebos were arguably in violation of AMA standards, including 18% who prescribed placebos “to
calm the patient”, 15% who did so “after ‘unjustified’ demand for medication”, and 6% who simply
wanted “to get the patient to stop complaining” (p. 8). In a similar vein, 63% of Swiss doctors
surveyed provided placebos “to conform with the requests of the patient” (Fassler et al., 2009, p. 5);
43% of Israeli doctors surveyed reported offering placebos to patients “after 'unjustified' demand for
medication”, and 11% did so “to get patient to stop complaining” (Nitzan & Lichtenberg, 2004, p. 945).
Particularly in surveys conducted outside the United States, most physicians actually told their patients
that placebo treatments were real drugs or therapies (Fassler et al., 2009; Nitzan & Lichtenberg, 2004).
These survey data indicate that both official and colloquial views on placebo usage are
extremely varied and difficult to reconcile. In general, however, in the discussion over how to properly
integrate placebos into modern medicine, there are two fundamental approaches to the issue: either
physicians can fully inform patients that they are being administered a placebo remedy, or they can
choose to cover up this truth, using varying degrees of concealment. To many, the concealment option
seems more intuitively in line with the nature of the placebo effect – that the patient must believe the
treatment is real in order for the effect to be activated. The problem with this approach is that such
Running Head: INTEGRAL PLACEBOS 41
deliberate concealment necessarily needs operate clandestinely under an official stance of open and
informed medical practice, as to formally permit the misleading of patients obviously would create a
The other possibility for an ethical placebo – the open-label approach – is at once the least-
making the inactive nature of the remedy explicit to patients or consumers. Little research has been
conducted on open-label placebos thus far, most probably because they present such a counter-intuitive
possibility to researchers. If the placebo effect relies on the subject not knowing a placebo is a placebo,
then were the subject fully informed, by definition a placebo should be rendered useless.
To my knowledge, only two studies have been conducted on open-label placebos, and neither
one provided definitive results. Park and Covi (1965) ran a study on 14 neurotic patients who were
given sugar pills over the course of a week, and who were told that “many people with your kind of
condition have also been helped by what are sometimes called 'sugar pills,' and we feel that a so-called
sugar pill may help you, too” (para. 14). Although its results seemed to show an average significant
improvement across trial participants, in light of its small sample size, and conducted over such a short
period of time, and without being replicated by subsequent independent follow-up, this study amounts
at most to an interesting footnote in placebo research. Sandler, Glesne, and Geller (2008) published a
10 To date, US courts have been somewhat ambivalent about the purposeful reliance on placebo effects in commercial
medical products. A 2006 federal district court ruling (and subsequent 2008 appellate court upholding) decided against QT,
Inc., a company which sold “Q-Ray” bracelets purported to have healing effects, but which were determined by a 2002
Mayo Clinic study to work no better than a placebo (Bratton et al., 2002; Sachdev, 2008). The appellate judges noted in
their opinion statement that the defendants invoked the reality of the placebo effect as part of their appeal, with the
argument that “the placebo effect vindicates their claims, even though they are false—indeed, especially because they are
false, as the placebo effect depends on deceit” (Easterbrook, Bauer, & Williams, 2008, p. 6). Although the judges came
down harshly on the defendants for fraudulent marketing practices, it is interesting to note that they did not completely
discount the theoretical validity of the placebo argument:
The Federal Trade Commission Act condemns material falsehoods in promoting consumer products; the
statute lacks an exception for “beneficial deceit.” We appreciate the possibility that a vague claim—along the lines
of “this bracelet will reduce your pain without the side effects of drugs”—could be rendered true by the placebo
effect. To this extent we are skeptical about language in FTC v. Pantron I Corp., 33 F.3d 1088 (9th Cir. 1994),
suggesting that placebo effects always are worthless to consumers. (Easterbrook et al., 2008, p. 6)
Running Head: INTEGRAL PLACEBOS 42
more robust study some 40 years later, on the use of placebos to enhance doses of medication for
children suffering from Attention Deficit Hyperactivity Disorder (ADHD). The study yielded
promising results – children who received half their normal dose of medication, plus a placebo
“booster” (and who were told ahead of time that the pill was not a real drug) responded similarly to
those who received a full dose of their normal medication. Still, this study is technically one which
evaluates placebos as drug performance enhancers, rather than as fully independent treatments in their
own right. It currently remains to be seen whether an open-label placebo treatment can independently
To summarize this section, it is clear that each of the placebo effect's four quadrants holds
numerous questions and possibilities for future research. More importantly, there is a distinct shift
away from a focus on the biological roots of health and healing (the individual-exterior quadrant), and
towards the subtler influences of personal belief, community values, and societal development
represented in the other three quadrants. For example, the apparent strengthening of the placebo effect
over time seems to be largely correlated with improvements in research technology, as well as patterns
of behavior in clinical trials – the domain of the collective-exterior. Closed-label placebos challenge
the medical profession's ethical comfort zone – the collective-interior – and open-label placebos raise
questions about exactly how patients' belief systems and understanding interact with the healing power
of simulated treatments – the individual-interior. With these complex issues looming on the horizon of
future placebo research, it seems all the more practical to contain them within a coherent framework for
understanding and integration – a framework such as the quadrant model of Integral Psychology.
Amidst the many references, stories, and ideas presented in this paper, if there is a core message
to take away from its reading, I would propose that it relates to a progression of three truths. Well,
Running Head: INTEGRAL PLACEBOS 43
three and a half, to be exact. First, to speak of what we know about the placebo effect is to speak of
what we know about medicine; second, we really don't know much about the placebo effect; and third,
in order to know more, we need to turn to other paradigms of logic, examination, and inquiry, outside
the boundaries of conventional science – paradigms including, but not limited to, integral and
transpersonal studies. In closing, I will spend a brief moment reviewing the case for each of these
Modern medical research follows a simple formula in determining what should and shouldn't be
accepted as a part of its practice. Using the best methodological and technological approach possbile, a
randomized clinical trial is designed and carried out, meant to test a new drug, procedure, or treatment.
If, at the end of the trial, the treatment in question has demonstrated conclusively that it works better
than a placebo, then it becomes a good candidate for acceptance into the medical canon. That's a bit of
an oversimplification – the same test will need to be run numerous times, and ideally be verified
independently by other researchers, in order to be fully accepted – but nevertheless, results from
But at the core of the core, there exists a crucial determining factor: the relative success or
failure of any treatment when compared to placebo treatment. The security of this relationship,
however, is dependent on the degree to which we can trust our assessment of the placebo effect. If a
new drug is determined to be 30% more effective than placebo, then it would appear to be a legitimate
treatment. But if we were to find out some time later that we had incorrectly measured the placebo
effect, and that it was in fact 30% stronger than it initially appeared (thus making it equally effective as
the active treatment), then that same drug we once would have accepted as genuine medicine would
now be considered a failure. This is the essence of the first truth: the better we can evaluate the placebo
effect in research and clinical settings, the better we will be able to evaluate the usefulness of proposed
Running Head: INTEGRAL PLACEBOS 44
new medicines, and, thus, medical science overall. I find it a particularly striking irony, that the more
our scientific endeavors produce technology capable of greatly refined observation, the more we see
As mentioned in Part Five, Silberman's (2009) article, along with Kirsch et al. (2008) and
others, imply that exactly these sorts of miscalculations mentioned in the previous section are now
coming to light. Pharmaceutical companies are terrified because more and more of their drugs are
failing to win out over placebos. There is credible evidence that placebo rates can vary wildly for the
same clinical research, based on geography, culture, and study design. Recalling the findings presented
in the Individual-Exterior section of Part Two, researchers have now found neurological networks in
the brain and the spine that carry real messages of relief and healing, specifically activated by placebo
stimuli. Some of these findings were literally published just weeks ago at the time of this writing.
After 60 years of serious research in the field, there are still at least as many questions as we have
answers, and the questions now seem to suggest stranger and stranger truths about the way our minds,
bodies, and environment co-exist. Remember, these three truths are progressive, they build upon one
another. If the second truth acknowledges that we are floundering in our nascent understanding of
placebos, then to tie it to this first truth is to admit that we are equally at a loss to understand the larger
To be fair, scientific inquiry has always excelled at validating the details, rather than the big
pictures. That's what science is designed to do. When enough details have been amassed, however,
there comes a point when a bigger picture is called for, in order to make sense of the many specifics.11
In the particular case of placebo studies, and, perhaps, for medicine as a whole, the four-quadrant
11 Whence the current thrust in recent decades for a grand, unified theory that brings order and relationship to the
seemingly disparate truths of Newtonian mechanics, quantum physics, and relativity, for example.
Running Head: INTEGRAL PLACEBOS 45
framework of Integral Psychology seems like a great place to start for creating greater order and
cohesive understanding. The four quadrants represent only a small part of the entire Integral vision,
and while a deeper investigation of such possibilities is unfortunately beyond the scope of this paper,
there are many further layers of subtlety and nuance that could apply here to medical research as well.
seems that some new alliance will need to be forged in the near future, one which bridges the strict but
precise orthodoxy of investigative science, and the broader ontological impressions of modern
psychology and philosophy. While the latter without the former may struggle to bring its ideas into
pragmatic application, the former without the latter seems doomed to a self-imploding course of ever-
Fortunately, this story ends on a happier note – or if not happier, then at least a lighter one.
If there is anything I have learned from my research into the placebo effect, it is that there are no truths
which can be held self-evident. (No, not even that one.) The combined wisdom from Integral
Psychology and placebo research provides clear evidence that what we think we know to be real is
actually founded upon a tenuous network of circumstance. Even the definition of the placebo effect
itself is based on elements which will inevitably shift, reorganize, and refine themselves in time. What
physiological context, and technological sophistication – all of which are both illusions and undeniable
realities at the same time! This is the final half-truth – the truth of the two simultaneous and
contradictory poles of knowing – and it is in this paradox that I find the ability to hold this and every
other truth a bit more lightly. All stories make new realities, as I hope I've been successful in
demonstrating with this one; at the same time, there are other stories being told at this very moment,
In closing, and as a thanks for reading, I offer you, the Reader, this benediction:
May the tale of your own inner world be filled with joyful adventure.
END
Running Head: INTEGRAL PLACEBOS 47
References
Abumrad, J., & Krulwich, R. (2007, May 18). Placebo. National Public Radio, WNYC podcast. Podcast
American Medical Association. (2007). Placebo use in clinical practice. American Medical
resources/medical-ethics/code-medical-ethics/opinion8083.shtml
Amanzio, M., Corazzini, L. L., Vase, L., & Benedetti, F. (2009). A systematic review of adverse events
doi:10.1016/j.pain.2009.07.010
Barsky, A. J., Saintfort, R., Rogers, M. P., & Borus, J. F. (2002). Nonspecific medication side effects
and the nocebo phenomenon. JAMA: The Journal of the American Medical Association, 287(5),
622-627.
Beecher, H. K. (1955). The powerful placebo. Journal of the American Medical Association, 159(17),
1602-1606.
Begley, S. (2007). Train your mind, change your brain. New York: Ballantine.
Bell, V. (2009, August 26). Placebo has strength in numbers. Message posted to
http://www.mindhacks.com/.
Benedetti, F. (1996). The opposite effects of the opiate antagonist naloxone and the cholecystokinin
Running Head: INTEGRAL PLACEBOS 48
doi:10.1016/0304-3959(95)00179-4
Benedetti, F. (2008). Mechanisms of placebo and placebo-related effects across diseases and
doi:10.1146/annurev.pharmtox.48.113006.094711
Benedetti, F. (2009). Placebo effects: Understanding the mechanisms in health and disease. New York:
Benedetti, F., Amanzio, M., & Maggi, G. (1995). Potentiation of placebo analgesia by proglumide. The
Benedetti, F., Arduino, C., & Amanzio, M. (1999). Somatotopic activation of opioid systems by target-
directed expectations of analgesia. The Journal of Neuroscience: The Official Journal of the
Benson, H., & Epstein, M. D. (1975). The placebo effect. A neglected asset in the care of patients.
Blackwell, B., Bloomfield, S., & Buncher, C. R. (1972). Demonstration to medical students of placebo
doi:10.1016/S0140-6736(72)90996-8
Branthwaite, A., & Cooper, P. (1981). Analgesic effects of branding in treatment of headaches. British
Bratton, R. L., Montero, D. P., Adams, K. S., Novas, M. A., McKay, T. C., Hall, L. J., Foust, J. G., et
al. (2002). Effect of "ionized" wrist bracelets on musculoskeletal pain: a randomized, double-
blind, placebo-controlled trial. Mayo Clinic Proceedings. Mayo Clinic, 77(11), 1164-1168.
Brody, H. (1999). The doctor as therapeutic agent: A placebo effect research agenda. In A. Harrington
(Ed.), The placebo effect: An interdisciplinary exploration. (pp. 77-92). Cambridge, MA:
Running Head: INTEGRAL PLACEBOS 49
Buske-Kirschbaum, A., Kirschbaum, C., Stierle, H., Lehnert, H., & Hellhammer, D. (1992).
Cobb, L. A., Thomas, G. I., Dillard, D. H., Merendino, K. A., & Bruce, R. A. (1959). An evaluation of
de Craen, A. J., Roos, P. J., Leonard de Vries, A., & Kleijnen, J. (1996). Effect of colour of drugs:
systematic review of perceived effect of drugs and of their effectiveness. BMJ (Clinical
de Craen, A. J., Kaptchuk, T. J., Tijssen, J. G., & Kleijnen, J. (1999). Placebos and placebo effects in
medicine: historical overview. Journal of the Royal Society of Medicine, 92(10), 511.
de Craen, A. J., Tijssen, J. G. P., de Gans, J., & Kleijnen, J. (2000). Placebo effect in the acute
treatment of migraine: subcutaneous placebos are better than oral placebos. Journal of
Crum, A. J., & Langer, E. J. (2007). Mind-set matters: Exercise and the placebo effect. Psychological
Dixon, D. M., Sweeney, K. G., & Gray, D. J. (1999). The physician healer: Ancient magic or modern
Easterbrook, Bauer, & Williams. (2008). Federal Trade Commission vs. QT, Inc., Q-Ray company
Bio-Metal,Inc., and Que Te Park. United States Court of Appeals, 7th Circuit. Retrieved from
http://www.ftc.gov/os/caselist/0323011/080103qtrayseventhcircuitappealruling.pdf
Eippert, F., Finsterbusch, J., Bingel, U., & Buchel, C. (2009). Direct evidence for spinal cord
Evans, D. (2004). Placebo: Mind over Matter in Modern Medicine. New York: Oxford University
Press.
Fässler, M., Gnädinger, M., Rosemann, T., & Biller-Andorno, N. (2009). Use of placebo interventions
among Swiss primary care providers. BMC Health Services Research, 9, 144.
doi:10.1186/1472-6963-9-144
de la Fuente-Fernandez, R. (2001). Expectation and dopamine release: Mechanism of the placebo effect
Goebel, M. U., Trebst, A. E., Steiner, J., Xie, Y. U., Exton, M. S., Frede, S., Canbay, A. L.,
Goffaux, P., Redmond, W. J., Rainville, P., & Marchand, S. (2007). Descending analgesia–When the
Gracely, R. H., Dubner, R., Deeter, W. R., & Wolskee, P. J. (1985). Clinicians' expectations influence
Gracely, R. H., Dubner, R., & McGrath, P. A. (1979). Narcotic analgesia: Fentanyl reduces the
intensity but not the unpleasantness of painful tooth pulp sensations. Science (New York, N.Y.),
203(4386), 1261-1263.
Grenfell, R. F., Briggs, A. H., & Holland, W. C. (1961). A double-blind study of the treatment of
hypertension. JAMA: The Journal of the American Medical Association, 176, 124-128.
Grevert, P., Albert, L. H., & Goldstein, A. (1983). Partial antagonism of placebo analgesia by
Gryll, S. L., & Katahn, M. (1978). Situational factors contributing to the placebo effect.
Running Head: INTEGRAL PLACEBOS 51
Guterl, F. (2001, June 18). How real is the placebo effect? Newsweek. 57-60.
Hahn, R. A. (1999). The nocebo phenomenon: Scope and foundations. In A. Harrington (Ed.), The
University Press.
Harrington, A. (Ed.). (1999). The placebo effect: An interdisciplinary exploration (1st ed.). Cambridge,
Harrington, A. (2009). The cure within: A history of mind-body medicine (Reprint.). New York: W.W.
Houston, W. R. (1938). The doctor himself as a therapeutic agent. Annals of Internal Medicine, 11(8),
1416-1425. doi:10.1059/0003-4819-11-8-1416
Hróbjartsson, A., & Gøtzsche, P. C. (2001). Is the placebo powerless? An analysis of clinical trials
comparing placebo with no treatment. The New England Journal of Medicine, 344(21), 1594-
1602.
Hróbjartsson, A., & Norup, M. (2003). The use of placebo interventions in medical practice--a national
questionnaire survey of Danish clinicians. Evaluation & the Health Professions, 26(2), 153-
165.
Hussain, M. Z., & Ahad, A. (1970). Tablet colour in anxiety states. British Medical Journal, 3(5720),
466.
Idler, E. L., & Kasl, S. (1991). Health perceptions and survival: do global evaluations of health status
doi:10.1053/gast.1997.v112.pm9178676
Kaplan, G. A., & Camacho, T. (1983). Perceived health and mortality: a nine-year follow-up of the
Kaptchuk, T. J., Kelley, J. M., Conboy, L. A., Davis, R. B., Kerr, C. E., Jacobson, E. E., Kirsch, I.
,...Lembo, A.J. (2008). Components of placebo effect: randomised controlled trial in patients
with irritable bowel syndrome. BMJ (Clinical Research Ed.), 336(7651), 999-1003.
doi:10.1136/bmj.39524.439618.25
kellyneil. (2009, March 23). Placebo: Healing the body with the mind (2 of 5) [Video File]. Video
posted to http://www.youtube.com/watch?v=_VjHJj01QH8
Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008).
Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and
Kirsch, I., & Sapirstein, G. (1998). Listening to Prozac but Hearing Placebo: A Meta-Analysis of
Kong, J., Gollub, R. L., Rosman, I. S., Webb, J. M., Vangel, M. G., Kirsch, I., & Kaptchuk, T. J.
functional magnetic resonance imaging. The Journal of Neuroscience: The Official Journal of
Lehrer, J. (2008, June 16). Shyamalan and the placebo effect : The frontal cortex. Message posted to
http://scienceblogs.com/.
Levine, J. D., Gordon, N. C., & Fields, H. L. (1978). The mechanism of placebo analgesia. Lancet,
Levine, J. D., & Gordon, N. C. (1984). Influence of the method of drug administration on analgesic
Lieberman, M. D., Jarcho, J. M., Berman, S., Naliboff, B. D., Suyenobu, B. Y., Mandelkern, M., &
Running Head: INTEGRAL PLACEBOS 53
Mayer, E. A. (2004). The neural correlates of placebo effects: a disruption account. NeuroImage, 22(1),
447-455. doi:10.1016/j.neuroimage.2004.01.037
Mark, D. (2009, July 1). The Placebo Effect Quantified. Nutraceuticals World. Retrieved November
http://www.nutraceuticalsworld.com/articles/2009/07/the-placebo-effect-quantified
Matre, D., Casey, K. L., & Knardahl, S. (2006). Placebo-induced changes in spinal cord pain
doi:10.1523/JNEUROSCI.4218-05.2006
Miller, G. (2008). Prescribing" placebo treatments": results of. British Medical Journal, 337, a1938.
Moerman, D. E. (1983). General medical effectiveness and human biology: Placebo effects in the
Moerman, D. E. (2000). Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure.
Moerman, D. E., & Jonas, W. B. (2002). Deconstructing the placebo effect and finding the meaning
Moseley, J. B., Wray, N. P., Kuykendall, D., Willis, K., & Landon, G. (1996). Arthroscopic treatment
Moseley, J. B., O'Malley, K., Petersen, N. J., Menke, T. J., Brody, B. A., Kuykendall, D. H.,
Hollingsworth, J. C., et al. (2002). A controlled trial of arthroscopic surgery for osteoarthritis of
Myers, C. (2009, September 4). Array BioPharma shares down on mid-stage RA trial failure. Fierce
biopharma-shares-down-mid-stage-ra-trial-failure/2009-09-04
Nitzan, U., & Lichtenberg, P. (2004). Questionnaire survey on use of placebo. BMJ (Clinical Research
Nordenberg, T. (2000, January). The healing power of placebos. Retrieved November 15, 2009,
from http://findarticles.com/p/articles/mi_m1370/is_1_34/ai_59111154/
Nunn, R. 2009. It’s time to put the placebo out of our misery. British Medical Journal 338, b1568.
palMD. (2009, September 3). Placebo is not what you think it is. Message posted to
http://scienceblogs.com/whitecoatunderground/
Park, L. C., & Covi, L. (1965). Nonblind placebo trial: An exploration of neurotic patients' responses to
placebo when its inert content is disclosed. Archives of General Psychiatry, 12, 36-45.
Parsons, H. M. (1974). What Happened at Hawthorne?: New evidence suggests the Hawthorne effect
Petrovic, P., Kalso, E., Petersson, K. M., & Ingvar, M. (2002). Placebo and opioid analgesia-- imaging
doi:10.1126/science.1067176
Rief, W., Nestoriuc, Y., von Lilienfeld-Toal, A., Dogan, I., Schreiber, F., Hofmann, S. G., Barsky, A.
J. (2009). Differences in adverse effect reporting in placebo groups in SSRI and tricyclic
doi:10.2165/11316580-000000000-00000
Sachdev, A. (2008, January 4). Multimillion judgment upheld in Q-Ray case. Chicago Tribune.
Salgo, P. (2006, March 22). The Doctor Will See You for Exactly Seven Minutes. The New York
Sandler, A. D., & Bodfish, J. W. (2008). Open-label use of placebos in the treatment of ADHD: a pilot
doi:10.1111/j.1365-2214.2007.00797.x
Schapira, K., McClelland, H. A., Griffiths, N. R., & Newell, D. J. (1970). Study on the effects of tablet
colour in the treatment of anxiety states. British Medical Journal, 1(5707), 446-449.
Shapiro, A. K., & Shapiro, E. (1999). The placebo: Is it much ado about nothing? In A. Harrington
(Ed.), The placebo effect: An interdisciplinary exploration. (pp. 12-36). Cambridge, MA:
Shaw, D. M. (2009). Prescribing placebos ethically: the appeal of negatively informed consent. Journal
Shaw, G. B. (1911). The Doctor's Dilemma. Retrieved November 15, 2009, from
http://www.gutenberg.org/files/5070/5070-h/5070-h.htm
Sherman, R., & Hickner, J. (2007). Academic Physicians Use Placebos in Clinical Practice and Believe
doi:10.1007/s11606-007-0332-z
Silberman, S. (2009, September). Placebos Are Getting More Effective. Drugmakers Are Desperate to
http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?currentPage=all
Talbot, M. (2000). The placebo prescription. New York Times Magazine, 9, 34–9.
Thomas, K. B. (1987). General practice consultations: is there any point in being positive? British
Thomas, W. J. (2001). Informed consent, the placebo effect, and the revenge of Thomas Percival. The
Running Head: INTEGRAL PLACEBOS 56
US Army. (n.d.). The Hippocratic Oath. US Army North American Regional Medical Command.
%20Library/The_Hippocratic_Oath.pdf
Vedantam, S. (2004, September 10). FDA Urged Withholding Data on Antidepressants. The
Washington Post, 2.
Visser, F. (2005). Ken Wilber: Thought as passion [Reprint]. Albany, NY: SUNY Press.
Vollmann, J., & Winau, R. (1996). Informed consent in human experimentation before the Nuremberg
Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., Kosslyn, S.
Wolf, S. (1950). Effects of suggestion and conditioning on the action of chemical agents in human
Zenit International News Agency. (1999, February 11). Authentication of a Cure at Lourdes. Retrieved
Znamenski, A. A. (2007). The beauty of the primitive. New York: Oxford University Press. Retrieved
from http://books.google.com/books?id=6uF00yUt3dYC&dq=quesalid+boas&source=
gbs_navlinks_s