Acta Psychiatr Scand 2015: 132: 227–230 © 2015 John Wiley & Sons A/S.
Wiley & Sons A/S. Published by John Wiley & Sons Ltd
All rights reserved
DOI: 10.1111/acps.12422
Editorial
Do cultures influence placebo response?
Introduction
Individuals are born in, work in and live in cul-
tures, which have a profound effect on their lives
and functioning. Cultures determine cognitive
schema and also how individuals express and deal
with distress – whether it is physical or emotional.
Cultures determine explanatory models of illness
that individuals hold and allocate health resources
as well as encourage individuals to follow certain
pathways into care and accept or reject health care.
Cultural variations in presentation of various
psychiatric disorders have been studied, but not
treatment responses as widely.
It is inevitable that dietary habits, simultaneous
use of alternative and complementary medicines
and other factors such as pharmacodynamics and
pharmacokinetics play a major role in acceptance
of pharmaceutical agents and treatment outcomes
across cultures.
In various cultural settings, patients and their
carers have varying expectations. In this editorial,
we explore the role of placebo response.
Placebo response
The placebo response itself is affected by a number
of factors (1). These include colour, name, appear-
ance, route of administration of drugs as well as
personality traits of patients (2). Both classical
conditioning (3) and information processing (4)
have been described as influencing placebo effect.
The term placebo derives from Latin, with its lit-
eral meaning being ‘I please’. Placebos have been
used for millennia and the term carries multiple
meanings and interpretations (5). The term does
carry negative meanings as well (6). It has been
argued that in spite of its perceived ‘inertness’,
patients do get better (7). These authors note that
Beecher’s original observation (8) that placebo
may work as a psychological instrument and as a
resource for the doctor and to study the mecha-
nisms of drug action still stands. From the early
days of randomised controlled trials where place-
bos and ‘active’ medications were compared, the
actual impact of placebo has not been clear, and
some of the reasons for this are described below.
ACTA PSYCHIATRICA SCANDINAVICA
Placebos have been used as controls (9). Price et al.
(10) define the placebo effect as the average
placebo response in a group of individuals and a
placebo response as the change in symptom or
condition occurring as a result of placebo. Media
and lay interpretations of placebo play an impor-
tant role in its acceptance.
Culture itself is described as the milieu within
which one is brought up and has distinct frame-
works, values and systems which not only give the
individual a sense of belonging but also provide a
sense of world view and values. It is critical that we
bear in mind that individuals carry multiple cul-
tural identities or micro-identities, which may
reflect in a number of ways, such as gender, institu-
tions, workplace and sexual orientation. Cultures
determine cognitive schema and interpretation of
symbols of relevance and importance within that
culture. This is the crux of understanding placebo
response. However, this aspect of placebo response
must be seen in the context of how patients per-
ceive their illness experiences – what names and
explanatory models they give to it, but also the
actual therapeutic communication and encounter.
It is clear that all these are strongly affected by
cultures.
Disease and illness: Doctors are trained to diag-
nose and treat diseases, whereas the social impact
of diseases is embedded in illnesses. Doctors focus
on organs and their dysfunction, whereas patients
see the impact of disease in their states of being
and social function (11). Diseases and illnesses do
not map distinctly onto each other (12). Thus,
seeing the social implications in the cultural con-
text is important. It is also likely that patients are
keen to seek healing for their illnesses and these
may be more attractive because they take into
account individual models of distress (13). Cul-
tures also influence explanatory models and
Kleinman (13) noted that in Taiwan patients
expected allopathic doctors to provide injections,
whereas Chinese doctors were expected to provide
herbal treatments, thus highlighting different
expectations.
Culture and Placebo: It has been argued that
placebos affect the illness more than they affect the
disease (14). Classical conditioning (15) and
227
Editorial
expectancy (16) are key aspects of placebo
response. Thompson et al. see expectancy as the
patient’s level of expectation that they will be
helped by the treatment. These authors argue that
expectancy is a fairly robust and comprehensive
model, thereby recognising the importance of the
therapeutic context through supporting expectancy
and triggering a placebo effect. In order to kick off
such responses, verbal instructions play a role, thus
confirming the role of communication in therapeu-
tic engagement. In many cultures, patients expect
their doctors to make the right decisions and look
after them, making the responsibility clear,
whereas in others, patients want to be given infor-
mation and expect joint decision-making where
they have equal say. Thompson et al. (7) suggest
that a related concept to expectancy is self-efficacy.
This depends upon the belief that one can success-
fully perform actions needed to achieve valued
outcomes.
Caspi (17) puts forward a model which sees the
therapeutic relationship between clinician and
patient as the key trigger to placebo response.
Caspi (17) proposes that clinicians may thus use
the process of the therapeutic encounter to re-
frame the patient’s concerns and health status in
ways that can instil hope. Brody (18) argues that
the practitioner plays a key role in providing an
explanation of what is wrong with the patient and
holding out a promise for the patient that no mat-
ter how bad things are, they will get better. This
dealing with ambiguity and holding hope for the
patient are key responsibilities of the psychiatrist
(19). The key is what meaning patients give to
their experiences and distress which are culturally
influenced. Two explanations have been offered in
understanding the placebo effect – its dynamic
effect and, secondly, that the placebo effect inter-
acts synergistically with other therapeutic ele-
ments (20).
Placebo effect has also been seen as offering a
meaning response, which means the psychological
or physiological effects of meaning in treatment of
illness (21). Visual perceptions and world views dif-
fer across cultures, and the links between biology
and culture require further exploration. It is possi-
ble that cultural variations in pharmacodynamics
and pharmacokinetics will affect responses to
placebo.
Colour of medication: Patients’ compliance of
medication and treatment is strongly influenced by
the role (they think) medicine plays (22). The size
and colour of the tablets are significant factors.
Blue is seen as depressant-sedative, and yellow as
stimulant antidepressants (23). Blue preparations
are more soothing; and red, pink or yellow as more
228
stimulating (24). De Craen et al. (25) confirmed
that stimulation was associated with medicine
which was marketed in hot colours (red, orange,
yellow), and antidepressants were marketed in cold
colours (blue, green, purple). In a study with vol-
unteer medical students, similar observations were
made (26). Expectations thus drive the placebo
effect (27). Where patients see their illness as hot or
cold, they will only accept medication which deals
with the heat or cold. Buckalew and Coffield (23)
demonstrated that white capsules were seen as
analgesics by Caucasians, but as stimulants by
African Americans, whereas black capsules were
seen as stimulants by Caucasians and as analgesics
by African Americans. Interestingly, among pas-
sive individuals who were intellectually oriented,
sedative agents produced higher (than expected)
levels of sedation (2).
Regrettably, in drug trials, these factors are
not taken into account. It has been demonstrated
that holidays and year of birth play a role in
patient responses (28), but drug trials do not
appear to take these factors into account.
In clinical practice a few decades ago, Neki
et al. (29, 30) observed that African patients had
varying expectations from psychiatrists in com-
parison with shamans who offered traditional
healing practices. In African cultures, there was
a clearly observed discrepancy between the Afri-
can illness and expectations from European cli-
nicians. The challenge for modern psychiatry is
to look at cultural variations and cultural differ-
ences and place these in the context of clinical
practice, patient expectations and therapeutic
encounters.
Ninnemann (31) raises some interesting points
about the role of ethnopsychopharmacology in
placebo effects. There is no doubt that discussion
of ethnic and racial differences and identities are
charged with irrational emotions. The emphasis on
genomics and development of psychopharmacoge-
nomics raises some significant issues, and cultural
differences therefore deserve further exploration in
the cultural, sociological and anthropological
contexts.
Kleinman (32) noted that, in spite of increasing
data from treatment outcome studies on the
effects of psychopharmacological medications,
the evidence remains less impressive. He emphati-
cally argues that cultural and psychosocial fac-
tors deserve more and better attention. Thus,
there is a clear challenge for regulators like the
Federal Drug Administration that any drug trials
take into account psychosocial impact of drug
trials and focus on cultural relativism. We know
that drug trials previously conducted had

recommended doses which were inappropriate for
many ethnic groups. Now, as ever increasing
numbers of trials are being conducted in eastern
Europe, China and India, it will be of special
interest to see whether recommended doses as a
result of these trials will work for other ethnic
populations elsewhere.
In social and cultural psychiatry, numerous fac-
tors have often been ignored and require further
exploration. It is important that medical and
patient understanding of expectations of each
other deserve further exploration, especially in
drug trials. Healing, its meanings and its rituals,
must be understood in the context of ‘modern’
allopathic medicine.
Cultural symbols and their meanings, for exam-
ple preference of some cultural groups for syrups
or injections or capsules, have to be understood.
All drug trials must explore these meanings while
conducting the trials. A stronger positive effort is
required to understand patient perspectives of
their distress, their expectations of (therapeutic or
otherwise) interventions and expectations of the
therapeutic encounter itself. This requires
cross-cultural work with many cultures in rapid
transition as a consequence of globalisation, rapid
industrialisation and urbanisation. Use of comple-
mentary and alternative medicines and their
simultaneous use will further make therapeutic
interactions complex.
To conclude, cultural factors are at the heart of
any individual’s functioning. Therapeutic expecta-
tions and therapeutic responses need to be under-
stood in the context of biocultural variations. The
cultural meanings of symbols embedded in the
medical treatment have to be explored and under-
stood in order to achieve better therapeutic
engagements and outcomes. Understanding
patients’ explanatory models, their expectations
and pathways into care will provide better out-
comes. Taking into account that more drug trials
are being conducted in Eastern Europe and Asia,
the time is ripe to explore mind–body interactions
and pharmacokinetic and pharmacodynamics dif-
ferences and place these in the context of placebo
response. Dietary habits, smoking patterns and the
use of other substances must be taken into account
when conducting drug trials.
D. Bhugra1 and A. Ventriglio2
1
Emeritus Professor of Mental Health & Cultural Diversity, Institute
of Psychiatry, Psychology and Neuroscience, King’s College London,
London, UK
2
Department of Mental Health ASUR, Area Vasta2, Regione
Marche, Department of Clinical and Experimental Medicine,
University of Foggia, Foggia, Italy
E-mail: Dinesh.bhugra@kcl.ac.uk
Editorial
References
1. Shapiro AK, Wilensky H, Struening E. Study of the pla-
cebo effect with a placebo test. Compr Psychiatry
1968;9:118–137.
2. Janke W. Response variability to psychotropic drugs. In:
Janke W, ed. Response variability to psychotropic drugs.
NY: Pergamon Press, 1983:118–137.
3. Foot D, Ridge D. Constructing the placebo effect in the
placebo wars: what is the way ahead? Health Soc Rev
2012;21:355–368.
4. Colloca L, Miller F. How placebo responses are formed:
a learning perspective. Philos Trans R Soc Lond B Biol Sci
2011;366:1859–1869.
5. McQueen D, Cohen S, St John-Smith P, Rampes H. Rethink-
ing placebo in psychiatry: the range of placebo effects.
Adv Psychiatr Treat 2013;19:162–170.
6. Huculak S. Attempting to define placebos and their effects:
a keywords approach. BioSocieties 2013;8:164–180.
7. Thompson JJ, Ritenbaugh C, Nichter M. Reconsidering the
placebo response from a broad anthropological perspec-
tive. Cult Med Psychiatry 2009;33:112–152.
8. Beecher HK. The Powerful placebo. JAMA
1955;159:1602–1606.
9. Kaptchuk TJ. Powerful placebo: the dark side of the rando-
mised controlled trial. Lancet 1998;351:1722–1725.
10. Price DD, Finnis DG, Benedetti F. A comprehensive
review of the placebo effect: recent advances and current
thought. Annu Rev Psychol 2008;59:565–590.
11. Eisenberg L. Disease and illness. Cult Med Psychiatry
1977;1:9–23.
12. Stoeckle J, Zola IK, Davidson G. The quantity and signifi-
cance of psychological distress in medical patients.
J Chronic Dis 1964;17:959–970.
13. Kleinman A. Medical and psychiatric anthropology and
the study of traditional medicine in modern Chinese
culture. Bull Inst Ethnol Acad Sinica 1975;39:107–123.
14. Miller FG, Colloca J, Kaputchnik T. The placebo effect:
illness and interpersonal healing. Perspect Biol Med
2009;52:518–539.
15. Siegel S. Explanatory mechanisms for placebo effect: pav-
lovian conditioning. In: Guess HA, Kleinman A, Kusek JW,
Engel LW, eds. The science of the placebo. London: BMJ
Books, 2002:133–157.
16. Pollo A, Amanzio M, Arslanian A, Casadio C, Maggi G,
Benedetti F. Response expectancies in placebo analgesia
and their clinical relevance. Pain 2001;93:77–84.
17. Caspi O. Activating the healing response. In: Rakel D, ed.
Integrative medicine, 3rd edn. Philadelphia: Saunders,
2012:703–710.
18. Brody H. The doctor as therapeutic agent. In: Harrington A,
ed. The placebo effect: an interdisciplinary exploration. Cam-
bridge, MA: Harvard University Press, 1999:77–92.
19. Bhugra D, Ventriglio A, Kuzman MR et al. EPA guidance
on the role and responsibilities of psychiatrists. Eur Psy-
chiatry, 2015;30:417–422.
20. Bootzin R, Caspi O. Explanatory mechanisms for placebo
effects. In: Guess HA, Kleinman A, Kusek JW, Engel LW,
eds. The science of the placebo: toward an interdis-
ciplinary research agenda. London: BMJ Books, 2002:
108–132.
21. Moerman DE. Meaning, medicine and the ‘placebo effect’.
NY: Cambridge University Press, 2002.
22. Buckalew LW, Sallis RE. Patient compliance and medica-
tion perception. J Clin Psychol 1986;42:49–53.
23. Buckalew LW, Coffield KE. An investigation of drug
expectancy as a function of capsule color and size and
229
Editorial
preparation form. J Clin Psychopharmacol 1982;2:245–
248.
24. Buckalew LW, Ross S. Relationship of perceptual charac-
teristics to efficacy of placebos. Psychol Rep 1981;1981:
955–961.
25. De Craen AJM, Ross PJ, De Vries AL, Kleijnen J. Effect of
colour of drugs: systematic review of perceived effect of
drugs and of their effectiveness. Br Med J 1996;313:1624–
1626.
26. Blackwell B, Bloomfield SS, Buncher CR. Demonstration
to medical students of placebo responses and non-drug
factors. Lancet 1972;1:1279–1282.
27. Justman S. Placebo: the lie that comes true. J Med Ethics
2013;39:243–248.
28. Kaptchuk TJ. Placebo studies and ritual theory: a compar-
ative analysis of Navajo, acupuncture and biomedical
230
healing. Philos Trans R Soc Lond B Biol Sci
2011;366:1849–1858.
29. Neki JS, Joinet B, Ndosi N, Kilonzo G, Hauli JG, Duvinage
G. Witchcraft and psychotherapy. Br J Psychiatry
1986;149:145–155.
30. Neki JS, Joinet B, Hogan M, Hauli JG, Kilonzo G. The
cultural perspective of therapeutic relationship: a view-
point from Africa. Acta Psychiatr Scand 1985;71:543–
550.
31. Ninnemann KM. Variability in the efficacy of psychophar-
maceuticals: contributions from pharmacogenomics,
ethnopsychopharmacology, and psychological and psychi-
atric anthropologies. Cult Med Psychiatry 2012;36:10–25.
32. Kleinman A. rebalancing academic psychiatry: why it
needs to open-and soon. Br J Psychiatry 2012;201:421–
422.