Placebo interventions, such as sugar pills or saline injections, can be vehicles of therapeutic responses, but not by virtue of containing medication or internal properties with the power to produce beneficial health outcomes. Instead, the placebo intervention—a placebo pill, saline injection, and the invasive procedure or device that works by virtue of the placebo effect—should be understood as a signal, or set of signals, which convey information. A placebo intervention is usually delivered within and surrounded by a context, which includes a host of cues that convey information with potential for producing therapeutic (and also counter-therapeutic nocebo) responses. In addition to the treatment ritual, these include the therapist's white coat, diagnostic instruments, the appearance of the therapist's office or hospital room, the words communicated by the therapist, the therapist's disposition in listening and responding to the patient, gestures and touch.
The patient does not come to the clinical encounter as a blank slate but with a history of experiences and memories evoked by prior responses to signals related to the milieu of therapy, some of which may influence the way in which the patient processes the information from signals emanating from the present clinical encounter. It is important to recognize that placebo responses are not limited to ‘inert’ placebo interventions. Proven effective treatments also function as signals, in addition to producing therapeutic effects based on their inherent pharmacological or physiological characteristics; and they are administered in the clinical encounter, with a potential to generate placebo responses that enhance the therapeutic benefit of the treatment.
On the philosophical level, Miller & Colloca [2
] suggested that Peirce's theory of signs [3
] can illuminate the placebo response as deriving from processes of decoding psychosocial signals. Peirce developed his theory of signs in an effort to provide a systematic understanding of logic, and his semiotic theory seems to apply to all forms of communication and learning, not only by humans but also other animals [3
]. According to Peirce's theory, signs convey information about objects to an interpreter. There is a triadic relationship between (i) the sign vehicle, (ii) the object it signifies and (iii) the interpreter who consciously or unconsciously decodes information produced by the sign. Peirce classifies signs into three types: (i) indices
, signs which are dynamically connected with their objects, and with the senses or memory of the individuals for whom they serve as signs; (ii) symbols
, signs which refer to the object that it denotes by virtue of a conventional rule, which causes the symbol to be interpreted as referring to that object, as in the use of language; and (iii) icons
, signs that signify their objects by virtue of a likeness between the sign and the object, such as diagrams, pictures and representations.
Each of these three forms of signs can be seen as operating in the formation of placebo responses. For example, in the domain of pain, the most important area of investigation of the placebo effect [4
], an experimental subject or a patient who experiences pain relief after being presented with a placebo described as an analgesic medication (‘This is a powerful painkiller’) is responding to this symbolic
communication and other signals (including index signs) that constitute the treatment ritual. Understanding this symbolic communication, the patient anticipates pain relief and may experience analgesia simply by virtue of this anticipation. The interpretation of symbols in communication between therapist and patient can also relieve anxiety, which often exacerbates suffering from illness. In the context of conditioning, a conditioned stimulus (CS) becomes an index which conveys information. Its object is the unconditioned stimulus (US), with which the CS has been paired. In general, by detecting the CS and learning the relation between it and the US, the subject anticipates the US and exhibits the conditioned response (CR). Thus, the conditioned placebo effect is a response to an index sign
that leads the individual to learn to experience a beneficial outcome, such as pain relief. Finally, icons are signs that signify their objects by virtue of a likeness between the sign and the object. An experimental observer who forms a placebo response following the observation of a simulator who demonstrates pain relief in response to a sham treatment can be understood as responding to an iconic sign
that conveys information about analgesia to the subject that leads him to produce a similar response ().
Figure 1. A learning perspective on placebo responses. The scheme shows how a set of signs including (i) indices (signs which are dynamically connected with their objects, and with the senses or memory of the individuals for whom they serve as conditioned stimuli); (more ...)
The exact mechanisms that transform the detection of signs into placebo responses are unknown: we can speculate that when placebo responses occur, the sign (or set of signs) that trigger these responses are interpreted and translated into neural input events and behaviour changes. Although there are differences across physiological systems and diseases, the diversity of placebo responses can be understood as generated by neural and psychobiological mechanisms based primarily on information processing and learning principles. Learning allows human individuals (and to some extent non-human animals) to combine distinctive elements of environmental and social cues with internal higher order functions (motivation, emotions and beliefs), which contribute to generating expectations and placebo responses.