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“The desire to take medicine is perhaps the greatest feature which distinguishes man from animals.”

—Sir William Osler


Henry Beecher's classic 1955 study “The Powerful Placebo” first attracted attention to the therapeutic effectiveness of placebo treatments in different painful conditions.1 Although the impressive effect size he attributed to the placebo effect was subsequently questioned given a lack of controls for natural history and regression to the mean, his article initiated a paradigm shift and opened up a new field of research. Further groundbreaking work demonstrated that placebo analgesia could be blocked by naloxone, which implied that endorphins were involved in this context.2 This work opened the path to a progressively greater understanding of what is now considered a psychobiological phenomenon. This chapter aims to review briefly the current knowledge of the psychology and neurophysiology underlying the placebo effect and then to focus on three main questions: (1) why the placebo effect is important in the practice of pain management; (2) what ethical considerations are raised by the clinical use of the placebo effect; and (3) how best to use the placebo effect for therapeutic purposes.

The term placebo is derived from the Latin for “I shall please” and originates from its use as an intervention aimed primarily at pleasing, rather than treating, the patient. Today, the word placebo is used in multiple contexts to refer to different but related concepts. Consequently, it has been extremely difficult for researchers to reach consensus on terminology in placebo studies, with even the term “the placebo effect” being raised as problematic (i.e., the placebo effect is the effect of something that has no effect). In this chapter, specific definitions are proposed and used (Box 18-1).

BOX 18-1 Key Terms

Placebo Treatment

  • “Pure placebo treatments” are inert substances (e.g., sugar pills or saline injections) or inactive physical interventions (e.g., sham surgical procedures or sham acupuncture).

  • “Impure placebo treatments” are active substances that do not provide any known benefit for the condition being treated (e.g., vitamin C for pain).

Placebo treatments can be used for two purposes:

  1. To control for an active treatment in a randomized clinical trial

  2. To elicit a physiological response known as the placebo effect

Placebo and Nocebo Effects

Positive or negative effects after administration of a placebo treatment that are independent of the natural course of the disorder.

  • Placebo effect → Improvement of the disorder

  • Nocebo effect → Worsening of the disorder or negative side effects

Placebo Analgesia

Decrease in pain after placebo treatment

Nonspecific Treatment Effects or Placebo-Related Effects

  • Effects elicited by an active treatment that are not attributable to the pharmacologic or physiological properties of a drug or intervention nor to the natural course of the disorder.

  • They are also referred to as “placebo-related effects” because these effects meet the criteria for a placebo effect but without the involvement of an actual ...

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