According to current pharmacological knowledge and the current understanding of cause and effect, a placebo contains no chemical (or any other agent) that could possibly cause any of the observed worsening in the subject's symptoms. Thus, any change for the worse must be due to some subjective factor.  Adverse expectations can also cause the analgesic effects of anesthetic medications to disappear.[7]

The worsening of the subject's symptoms or reduction of beneficial effects is a direct consequence of their exposure to the placebo, but those symptoms have not been chemically generated by the placebo. Because this generation of symptoms entails a complex of "subject-internal" activities, in the strictest sense, we can never speak in terms of simulator-centered "nocebo effects," but only in terms of subject-centered "nocebo responses."

Although some observers attribute nocebo responses (or placebo responses) to a subject's gullibility, there is no evidence that an individual who manifests a nocebo/placebo response to one treatment will manifest a nocebo/placebo response to any other treatment; i.e., there is no fixed nocebo/placebo-responding trait or propensity.

McGlashan, Evans & Orne (1969, p. 319) found no evidence of what they termed a "placebo personality." Also, in a carefully designed study, Lasagna, Mosteller, von Felsinger and Beecher (1954), found that there was no way that any observer could determine, by testing or by interview, which subject would manifest a placebo reaction and which would not.  Experiments have shown that no relationship exists between an individual's measured hypnotic susceptibility and their manifestation of nocebo or placebo responses.[8]

Causes[edit]

The term "nocebo response" was coined in 1961 by Walter Kennedy (he actually spoke of a "nocebo reaction").

He had observed that another, entirely different and unrelated, and far more recent meaning of the term "placebo" was emerging into far more common usage in the technical literature (see homonym), namely that a "placebo response" (or "placebo reaction") was a "pleasant" response to a real or sham/dummy treatment (this new and entirely different usage was based on the Latin meaning of the word placebo, "I shall please").

Kennedy chose the Latin word nocebo ("I shall harm") because it was the opposite of the Latin word "placebo", and used it to denote the counterpart of the placebo response: namely, an "unpleasant" response to the application of real or sham treatment.[citation needed]

Kennedy very strongly emphasized that his specific usage of the term "nocebo" did not refer to "the iatrogenic action of drugs":[9] in other words, according to Kennedy, there was no such thing as a “nocebo effect,” there was only a "nocebo response".

He insisted that a nocebo reaction was subject-centered, and he was emphatic that the term nocebo reaction specifically referred to "a quality inherent in the patient rather than in the remedy."[9]

Even more significantly, Kennedy also stated that while "nocebo reactions do occur [they should never be confused] with true pharmaceutical effects, such as the ringing in the ears caused by quinine".[9]

 

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