Summary of: Benedetti, F., & Amanzio, M. (2011). The placebo response: how words and rituals change the
patient's brain. Patient education and counseling, 84(3), 413-419.
The Placebo Response: How Words and Rituals Change the Patient‘ s Brain
medical treatment has usually two components: specific effect of treatment itself and the
perception that the therapy is being administered (placebo effect/response)
placebos can mimic, enhance, mask or prevent the beneficial responses to pharmacological
agents
placebo effect: result of positive expectations → observed in the placebo arm of a clinical
trial, and is produced by the placebo biological phenomenon in addition to other potential
factors contributing to symptom amelioration, such as natural history (the time course of a
symptom or disease in the absence of any external intervention), regression to the mean,
biases, judgment errors
placebo response: biological phenomenon in isolation → can best be studied in specifically
designed experimental protocols
nocebo effect: result of negative expectations, specific or generic (like a pessimistic attitude)
placebo/nocebo-related effect: raising expectations in the complete absence of a treatment,
just by inducing expectations
1. The Psychological Explanation
placebo and nocebo effects need not be mutually exclusive and can work simultaneously
1. placebo effect as an example of classical conditioning
◦ clinical setting can act as conditioned stimuli, eliciting a therapeutic response in absence
of active principle, just because they have been paired with it in the past
◦ same can occur for nocebo effect (e.g. nausea can be elicited by the sight of the
environment where chemotherapy has been administered in the past)
◦ Classical conditioning seems to work best where unconscious processes are at play, as in
placebo/nocebo effects involving endocrine or immune systems, but it has also been
documented in clinical and experimental placebo analgesia and nocebo hyperalgesia
2. expectations, generated as the product of cognitive engagement, when the patient
consciously foresees a positive/negative outcome, based on factors such as verbal
instructions, environmental clues, emotional arousal, previous experience, the interaction
with care-providers → anticipation of future outcome triggers internal changes resulting in
specific experiences
◦ e.g. study showed that all patients receiving a physiological solution, those who believed
that they would receive an analgesic drug demanded significantly less pain reliever than
those who believed that they would receive no analgesic at all (expectation of forth
going pain)
◦ expectation of forth going pain can further be modulated by number of emotional and
cognitive factors (e.g. desire, self-efficacy, self-reinforcing feedback)
◦ anxiety reduction also plays a role in placebo responses, because the subject
interpretation of ambiguous sensations is turned from harmful and threatening to benign
and unworthy of attention
◦ expectation of reward as contributor to genesis of placebo effects → expected clinical
benefit is a form of reward, which triggers the placebo response
2. The Neurobiological Explanation
in 1978 found that opiate antagonist naloxone was able to reduce the placebo response in
dental postoperative pain → first indication that endogenous opioids were involved in
placebo analgesia
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