Annals of Internal Medicine 2002 (Mar 19); 136 (6): 471–476 ~ FULL TEXT
Daniel E. Moerman, PhD, and Wayne B. Jonas, MD
Department of Anthropology,
University of Michigan-Dearborn,
6515 Cherry Hill Road,
Ypsilanti, MI 48198, USA.
We provide a new perspective with which to understand what for a half century has been known as the "placebo effect." We argue that, as currently used, the concept includes much that has nothing to do with placebos, confusing the most interesting and important aspects of the phenomenon. We propose a new way to understand those aspects of medical care, plus a broad range of additional human experiences, by focusing on the idea of "meaning," to which people, when they are sick, often respond. We review several of the many areas in medicine in which meaning affects illness or healing and introduce the idea of the "meaning response." We suggest that use of this formulation, rather than the fixation on inert placebos, will probably lead to far greater insight into how treatment works and perhaps to real improvements in human well-being.
From the FULL TEXT Article:
[The cure for the headache] was a kind of leaf, which required
to be accompanied by a charm, and if a person would repeat
the charm at the same time that he used the cure, he would be
made whole; but that without the charm the leaf would be of
— Socrates, according to Plato 
There is a renewed interest in placebos and the placebo
effect — on their reality, their ethics, their place
in medicine, or not, both in and out of the clinic and
academy. The U.S. National Institutes of Health recently
sponsored a large conference called “Science of the Placebo”.  At least five serious books on the subject [3-7] plus a book of poetry  and a novel  — each titled Placebo Effect — have been published since
1997. In the past 10 years, the National Library of Medicine
has annually listed an average of 3972 scholarly
papers with the keywords “placebo,” “placebos,” or “placebo
effect,” with a low of 3362 papers in 1992 and a
high of 4814 in 2000. During the fall of 2000, a discussion
of the effect of new “drag free” suits, which
might give an edge to Olympic swimmers, appeared in
US News and World Report: “[S]wimming officials aren’t
convinced this is anything more than the placebo effect.
Swimmers excel because they think they’ve got an edge”.  One widely reported study, which concluded that placebos were powerless , or represented the Wizard of Oz , occasioned a blizzard of criticism [13-26]
and some support.  It’s in the papers. [28, 29] It’s in
Yet the most recent serious attempt to try logically
to define the placebo effect failed utterly.  Given the
ways people have gone about it, this seems unsurprising.
Arthur K. Shapiro, MD, who spent much of his career
as a psychiatrist studying the placebo effect, recently
A placebo is a substance or procedure . . . that is objectively
without specific activity for the condition being
treated . . .
The placebo effect is the . . . therapeutic
effect produced by a placebo. 
If we replace the word “placebo” in the second sentence
with its definition from the first, we get: “The
placebo effect is the therapeutic effect produced by
[things] objectively without specific activity for the condition
being treated.” This makes no sense whatsoever.
Indeed, it flies in the face of the obvious. The one thing
of which we can be absolutely certain is that placebos do
not cause placebo effects. Placebos are inert and don’t
Moreover, people frequently expand the concept of
the placebo effect very broadly to include just about
every conceivable sort of beneficial biological, social, or
human interaction that doesn’t involve some drug wellknown
to the pharmacopoeia. A narrower form of this
expansion includes identifying “natural history” or “regression
to the mean” (as we might observe them in a
randomized, controlled trial) as part of the placebo effect.
But natural history and regression occur not only in
the control group. Nothing in the theory of regression
to the mean  hints that when people are selected for
being extreme on some measure (blood pressure or cholesterol,
for example), they are immune to regression if
they receive active treatment. Such recipients are as
likely (or unlikely) to move toward homeostasis as are
control group patients. So, regression to the mean is in
no meaningful way a “placebo effect.” Ernst and Resch  took an important step in trying to clarify this situation by differentiating the “true” from the “perceived”
placebo effect. But “true placebo effect” hasn’t
really caught on as a viable concept.
The concept of the placebo effect has been expanded
much more broadly than this. Some attribute the effects of
various alternative medical systems, such as homeopathy  or chiropractic , to the placebo effect. Others have
described studies that show the positive effects of enhanced
communication, such as Egbert’s , as “the placebo response
without the placebo”. 
No wonder things are confusing.
MEANING AND MEDICINE
We suggest thinking about this issue in a new way.
A group of medical students was asked to participate in
a study of two new drugs, one a tranquilizer and the
other a stimulant (36). Each student was given a packet
containing either one or two blue or red tablets; the
tablets were inert. The students’ responses to a questionnaire
1) the red tablets acted as stimulants while the blue ones acted as depressants and
2) two tablets had more effect than one. The students were not responding to the inertness of the tablets.
Moreover, these responses cannot be easily accounted for by natural history, regression to the mean, or physician enthusiasm (presumably the experimenters were as enthusiastic about the reds as the blues). Instead, they can be explained by the “meanings” in the experiment:
1) Red means “up,” “hot,” “danger,” while blue means “down,” “cool,” “quiet” and
2) two means more than one. These effects of color [37-40] and number [41, 42] have been widely replicated.
In a British study, 835 women who regularly used
analgesics for headache were randomly assigned to one
of four groups.  One group received aspirin labeled
with a widely advertised brand name (“one of the most
popular” analgesics in the United Kingdom that had
been “widely available for many years and supported by
extensive advertising”). The other groups received the
same aspirin in a plain package, placebo marked with
the same widely advertised brand name, or unmarked
placebo. In this study, branded aspirin worked better
than unbranded aspirin, which worked better than
branded placebo, which worked better than unbranded
placebo. Among 435 headaches reported by branded
placebo users, 64% were reported as improved 1 hour
after pill administration compared with only 45% of the
410 headaches reported as improved among the unbranded
placebo users. Aspirin relieves headaches, but so
does the knowledge that the pills you are taking are
In a study of the benefits of aerobic exercise, two
groups participated in a 10-week exercise program. One
group was told that the exercise would enhance their
aerobic capacity, while the other group was told that the
exercise would enhance aerobic capacity and psychological
well-being. Both groups improved their aerobic
capacity, but only the second group improved in psychological
well-being (actually “self-esteem”). The researchers
called this “strong evidence . . . that exercise
may enhance psychological well-being via a strong placebo
In the red versus blue pill study, we can correctly (if
not very helpfully) classify the responses of the students
as “placebo effects” because they did indeed receive inert
tablets; it seems clear, however, that they responded not
to the pills but to their colors. In the second study, the
presence of the brand name enhanced the effect of both
the inert and the active drug. It doesn’t seem reasonable
to classify the “brand name effect” as a “placebo effect”
because no placebos are necessarily involved. Meanwhile,
calling the consequences of authoritative instruction
to the exercisers a “placebo effect” could come only
from someone who believes that words do not affect the
world, someone who has never been told “I love you” or
who has never read the reviews of a rejected grant proposal.
It seems reasonable to label all these effects (except,
of course, of the aspirin and the exercise) as “meaning
responses,” a term that seeks, among other things, to
recall Dr. Herbert Benson’s “relaxation response”. 
Ironically, although placebos clearly cannot do anything
themselves, their meaning can.
We define the meaning response as the physiologic or
psychological effects of meaning in the origins or treatment
of illness; meaning responses elicited after the use of inert or
sham treatment can be called the “placebo effect” when
they are desirable and the “nocebo effect”  when they
are undesirable. This is obviously a complex notion with
several terms that would be challenging to unpack (“desirable,”
“effect,” “meaning,” “treatment,” “illness”) — an exercise that cannot be carried out here. Note that this
definition excludes several elements that are usually included
in our understanding of the placebo effect, such
as natural history, regression, experimenter or subject
bias, and error in measurement or reporting. Note as
well that the definition is not phrased in terms of “nonspecific”
effects; although many elements of the meaning
response or placebo effect may seem nonspecific,
they are often quite specific in principle after they are
Meaning Permeates Medical Treatment
Insofar as medicine is meaningful, it can affect patients,
and it can affect the outcome of treatment. [47-49] Most elements of medicine are meaningful, even if
practitioners do not intend them to be so. The physician’s
costume (the white coat with stethoscope hanging
out of the pocket) , manner (enthusiastic or not),
style (therapeutic or experimental), and language 
are all meaningful and can be shown to affect the outcome;
indeed, we argue that both diagnosis  and
prognosis  can be important forms of treatment.
Many studies can be cited to document aspects of the
therapeutic quality of the practitioner’s manner.  In
one, a strong message of the effect of a drug (an inert
capsule) substantially reduced the patients’ report of the
pain of mandibular block injection compared with the pain
after a weak message. Patients who received the weak message
reported less pain than a group that received no placebos
and no message at all.  In another study, 200
patients with symptoms but no abnormal physical signs
were randomly assigned to a positive or a negative consultation.
In a survey of patients 2 weeks later, 64% of patients
in the positive consultation group said they were all
better, while only 39% of those who had negative consultations
thought they were better. 
Although there is strong evidence for such “physician
effects,” little evidence shows that “patient effects”
are very important. A mass of research in the 1970s
designed to identify “placebo reactors” produced only
inconsistent and contradictory findings. [57-59]
Meaning Can Have Substantial Physiologic Action
Placebo analgesia can elicit the production of endogenous
opiates. Analgesia elicited with an injection of
saline solution can be reversed with the opiate antagonist
naloxone and enhanced with the opiate agonist proglumide.  Likewise, acupuncture analgesia can be
reversed with naloxone in animals  and people. 
To say that a treatment such as acupuncture “isn’t better
than placebo” does not mean that it does nothing.
Meaning and Surgery
The classic example of the meaningful effects of surgery
comes from two studies of ligation of the bilateral
internal mammary arteries as a treatment for angina. [63, 64] Patients receiving sham surgery did as well — with 80% of patients substantially improving — as those receiving
the active procedure in the trials or in general
practice. Although the studies were small, the procedure
was no longer performed after these reports were published.
Of note, these effectiveness rates (and those reported
by the proponents of the procedure at the time)
are much the same as those achieved by contemporary
treatments such as coronary artery bypass or β-blockers.
Some observers have suggested that the success of
transmyocardial laser revascularization, a procedure
without a clear mechanism, may be explained by what
they call the placebo effect  but what we call the
meaning response. This is a plausible interpretation of a
recent trial showing dramatic improvement in very sick
people in both participant groups of a control trial of
transmyocardial laser revascularization (Leon MB, Baim
DS, Moses JW, Laham RJ, Knopf W. A randomized
blinded clinical trial comparing percutaneous laser myocardial
revascularization [using Biosense LV Mapping]
vs. placebo in patients with refractory coronary ischemia.
Presented at American Heart Association Scientific Session,
12–15 November 2000).
Surgery is particularly meaningful: Surgeons are
among the elite of medical practitioners; the shedding of
blood is inevitably meaningful in and of itself. In addition,
surgical procedures usually have compelling rational
explanations, which drug treatments often do not.
The logic of arthroscopic surgery (“we will clean up a
messy joint”) is much more sensible and understandable
(and even effective ), especially for people in a culture
rich in machines and tools, than is the logic of
nonsteroidal anti-inflammatory drugs (which “inhibit
the production of prostaglandins which are involved in
the inflammatory process,” something no one would
ever tell a patient). Surgery clearly induces a profound
meaning response in modern medical practice. [67-69]
MEANING, CULTURE, AND MEDICINE
Anthropologists understand cultures as complex
webs of meaning, rich skeins of connected understandings,
metaphors, and signs. Insofar as
1) meaning has biological consequence and
2) meanings vary across cultures, we can anticipate that biology will differ in different places, not because of genetics but because of these entangled ideas;
we can anticipate what Margaret Lock
has called “local biologies” [70, 71]; Lock has shown
dramatic cross-cultural variation in the existence and experience
of “menopause”. [70, 71] Moreover, Phillips
has shown that “Chinese Americans, but not whites, die
significantly earlier than normal (1.3 to 4.9 y) if they
have a combination of disease and birth year which Chinese
astrology and medicine consider ill fated”. 
Among Chinese Americans whose deaths were attributed
to lymphatic cancer (n = 3041), those who were
born in “Earth years” — and consequently were deemed
by Chinese medical theory to be especially susceptible to
diseases involving lumps, nodules, or tumors — had an
average age at death of 59.7 years. In contrast, among
those born in other years, age at death of Chinese Americans
with lymphatic cancer was 63.6 years — nearly 4
years longer. Similar differences were also found for various
other serious diseases. No such differences were evident
in a large series of “whites” who died of similar
causes in the same period.
The intensity of the effect was
shown to be correlated with “the strength of commitment
to traditional Chinese culture.” These differences
in longevity (up to 6% or 7% difference in length of
life!) are not due to having Chinese genes but to having
Chinese ideas, to knowing the world in Chinese ways.
The effects of meaning on health and disease are not
restricted to placebos or brand names but permeate life.
One of us has shown variation in the response of
control groups to inert medication in diverse cultures for
the same conditions (ulcers, hypertension, and anxiety).  The Figure shows the relationship between control
group and active treatment group healing for endoscopically
diagnosed duodenal ulcer treated with antisecretory
medication. Control group healing and active treatment
group healing seem functionally related in these
The correlation between control and active healing
rates is 0.49; as the placebo group’s healing rate
increases, so does the rate of the active treatment group.
Although the average control group healing rate in five
German studies has been 62.4%, the healing rate was
16.7% in three studies from neighboring Denmark and
the Netherlands. The number needed to treat for benefit
(NNTB), to obtain ulcer healing, can be calculated; for
ulcer patients treated with placebo, the NNTB for those
who are German (not Danish or Dutch) is 2.
Practitioners can benefit clinically by conceptualizing
this issue in terms of the meaning response rather
than the placebo effect. Placebos are inert. You can’t do
anything about them. For human beings, meaning is
everything that placebos are not, richly alive and powerful.
However, we know little of this power, although
all clinicians have experienced it. One reason we are so
ignorant is that, by focusing on placebos, we constantly
have to address the moral and ethical issues of prescribing inert treatments [73, 74], of lying , and the like.
It seems possible to evade the entire issue by simply
avoiding placebos. One cannot, however, avoid meaning
while engaging human beings. Even the most distant
objects—the planet Venus, the stars in the constellation
Orion—are meaningful to us, as well as to others. 
Yet, a huge puzzle remains: Obviously the meaning
response is of great value to the sick and the lame. For
example, eliciting the meaning response requires remarkably
little effort (“You will be fine, Mr. Smith”). So
why doesn’t this happen all the time? And why can’t you
do it to yourself? Psychologist Nicholas Humphrey has
suggested that this conundrum may have evolutionary
roots: Healing has its benefits but also its costs. 
(For example, relieving pain may encourage premature
activity, which could exacerbate the injury. Moreover,
immune activity is metabolically very demanding on an
injured system.) Perhaps only when a friend, relative, or
healer indicates some level of social support (for example,
by performing a ritual) is the individual’s internal
economy able to act. Moreover, as we have clarified,
routinized, and rationalized our medicine, thereby relying
on the salicylates and forgetting about the more
meaningful birches, willows, and wintergreen from
which they came — in essence, stripping away Plato’s
“charms” — we have impoverished the meaning of our
medicine to a degree that it simply doesn’t work as well
as it might any more. Interesting ideas such as this are
impossible to entertain when we discuss placebos; they
spring readily to mind when we talk about meaning.
In part by a grant from the National Science Foundation to Dr. Moerman (NSF SBR-9421128).
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