The Curse of the Nocebo Effect

The placebo effect is a universally acknowledged phenomenon. In essence, if you think something is going to make you better, it probably will. If you believe that three tablets will do you more good than two, this may prove to be the case; if you believe that capsules are more effective than tablets, this may become your experience; and if you believe that expensive branded medicine must be better than the cheaper generic; this may turn out to be money well spent.

By contrast, the placebo’s darker cousin, the nocebo, is much less well researched and is rarely considered in clinical practice. The term nocebo is taken from Latin for “I will harm”* and was first formalized in the 1960s to mean something that rationally should have no effect but actually causes a deterioration in health. The difficulty in researching the nocebo effect arises because ethics review committees tend to take a dim view of trials in which an intervention is likely to cause actual harm to the subjects.

There are many anecdotal examples of the nocebo effect at work. For example, a nocebo response may explain the phenomenon of the voodoo curse in which a victim dies only because a belief in the power of the witch doctor has been so ingrained that, after he has been hexed, the target simply cannot believe that he will live. Other cases have been reported in which a patient has died after having been given a terminal prognosis; only for a post-mortem to reveal no such fatal disease was present. A few scientific studies have also looked at the phenomenon, including one in which volunteers were told that the researchers were looking for a link between mobile phone usage and the incidence of headaches. Throughout the trial a number of users reported headaches, even when (unbeknown to them), the phone they were using was actually an empty shell.

Patients taking pharmaceutical drugs often report unwanted and nonspecific adverse effects that cannot be attributed to the pharmacological action of the medicine. In a review of studies examining the reported side effects from pharmacological treatments, several factors were found to be associated with an increase in the number of such reports, including the patient’s expectations of adverse effects at the outset of treatment; a patient’s prior experience with certain treatments; and particular psychological characteristics such as anxiety and depression.

Although poorly understood, physiological explanations of the nocebo effect have been proposed. It has been shown, for example, that a patient’s anticipation of worsening pain causes an increase in anxiety which triggers the activation of cholecystokinin that, in turn, facilitates pain transmission. This response generates a vicious circle of anxiety and pain which may be one explanation of the nocebo effect.

The nocebo effect has important implications for clinical practice, and there are several measures that physicians and other practitioners can adopt to limit its damaging effects. Health care professionals should try to identify in advance those patients most at risk of the nocebo effect, they should choose their language carefully in consultations with patients, so as not to generate any self-defeating attitude in the patient, and they should always consider that nonspecific side effects of drug treatments may be due to the nocebo effect, and manage accordingly.

Placebo and nocebo are two sides of the same coin. A strong relationship and effective dialogue between doctor and patient can take advantage of any placebo response while mitigating any response from its darker and opposite number, the nocebo effect.

*The term placebo, meaning “I will please,” dates back to the 18th century.


Barsky AJ, Saintfort R, Rogers MP, Borus JF. Nonspecific medication side effects and the nocebo phenomenon. JAMA. 2002;287:622-7. DOI: 10.1001/jama.287.5.622

Colloca L, & Benedetti F (2007). Nocebo hyperalgesia: how anxiety is turned into pain Curr Opin Anaesthesiol, 20, 435-439 DOI: 10.1097/ACO.0b013e3282b972fb

Oftedal G, Straume A, Johnsson A, Stovner LJ. Mobile phone headache: a double blind, sham-controlled provocation study. Cephalalgia. 2007;27:447-55. DOI: 10.1111/j.1468-2982.2007.01336.x

  • A placebo (Latin for “I shall please”) is a pharmacologically inert substance (such as saline solution or a starch tablet) that produces an effect similar to what would be expected of a pharmacologically active substance (such as an antibiotic). By extension, “fake” surgery and “fake” therapies are considered placebos.

    Maimonides recommended in his Treatment of Sexual Disorders urinating into a hollow carrot as a cure for impotence. Well into the 17th century, the London Pharmacopoeia (as much of an authority as existed then) listed among its medicinal agents such things as the saliva of a fasting man, lozenges of dried viper, fox lungs and shed snake’s skin and sutures of the skull of an executed criminal among others.

    In 1939, long before high-tech drugs came along to treat the chest pain known as angina, an Italian surgeon named Fieschi devised a simple technique. Reasoning that increased blood flow to the heart would ease his patients’ pain, he made tiny incisions in their chests and tied knots in two arteries. The results were spectacular. Three quarters of all patients improved.” One third were cured.

  • Babba

    “The placebo effect is a universally acknowledged phenomenon.”

    That is not correct.

    The nature and size of the placebo/nocebo effect is still not clear. The work of Hróbjartsson and Gøtzsche in the last few years has raised serious questions about the conventional view of this phenomenon, and indeed its very existence (at least in some situations in which it was previously assumed to be in operation). While their work is by no means the final word, its full implications have yet to sink in for medical science and clinical practice.

    As somebody who is quite familiar with an area of medicine where notions of nocebo are frequently thrown around, I find the profession’s often hasty, uncritical, and convenient use of this concept a little disturbing. A fair chunk of bad medical theory and practice is covered up by invoking placebo/nocebo, with no proof at all offered for the specific invocation, especially in the clinic.

    It really is not justified to assume that placebo/nocebo occurs in any given situation, or that its effect is clinically significant, especially on a sustained basis. Applying notions of placebo effect in clinical practice is probably unethical at this point.

    This is one fad clinicians should be very wary of succumbing to.

    (And to be blunt, from behind the safety of internet anonymity, I am not that impressed by the work of Barsky and Borus. I think a lot more critical an appraisal of their views is required. I find their stuff quite ideological at times. More hard data, and less speculation, please.)


  • elivioma

    Its simply impossibly to prove any theory. But still useful to ponder it’s implications. Hard data does not = fact, any more than ideological speculation. I think it bodes the medical field well to explore these effects.

  • Babba

    “Hard data does not = fact, any more than ideological speculation.”

    Hard data is a lot closer to fact than is ideological speculation.

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Rachel Danks, PhD

Rachel Danks, PhD, is a freelance medical writer and editor with over 12 years of experience in the field. She has written and edited numerous academic papers, and is experienced in preparing marketing materials, educational resources and regulatory documents. Her clients include medical education groups, advertising agencies, pharmaceutical companies and academic institutions.

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