The Placebo Effect; how does it work?

There was an interesting discussion recently posted on the neurophysiologist Dr. Marcello Costa’s blog about the nature of the placebo and nocebo effects. See:

Basically, he argues a well researched position that there is now consideable evidence showing expectations to get better have significant effects on how patients actually feel, and gives some suggested physiological explanations of the phenomena.

We hear a lot about the placebo effect, so what is it?

A placebo (Latin for “to please”) is the measurable, observable, or experienced improvement in health or behavior not attributable to a medication or invasive treatment that has been administered.

It is frequently argued (see  for example) that the placebo effect is not really mind over matter; and has become a catchall term for a positive change in health not attributable to a therapeutic intervention.

The change seen with placebos has been suggested to be due to a number of things:

1) Regression to the mean –  the fascinating statistical phenomenon that if a variable is extreme on its first measurement, it will tend to be closer to the average on a second measurement. A 2004 paper by Barnett et al. has a good explanation (Barnett et al, 2005). Regression to the mean is another reason why we need repeat studies to reinforce findings.

2) Spontaneous Resolution – Leave people alone and frequently they often get better without any therapeutic interventions (much to the chagrin of many surgeons)! A proportion of the population will naturally resolve an illness without treatment. This is a good argument for minimizing interventions, vs. the “lets throw the kitchen sink at this health problem” approach.

3) Reduction of psychological stress (stress has a direct physiological link through the neuro-endocrine response) and a reduction of stress can have positive physiological benefits.

4) Misdiagnosis – frequently conditions are misdiagnosed (especially in early phases), and differential diagnosis remains as much an art as a science

5) Subject expectancy e.g. classical conditioning. Remember Pavlov?

The Placebo effect is nicely characterized by this quote:

“The physician’s belief in the treatment and the patient’s faith in the physician exert a mutually reinforcing effect; the result is a powerful remedy that is almost guaranteed to produce an improvement and sometimes a cure.” — Petr Skrabanek and James McCormick, Follies and Fallacies in Medicine, p. 13.

In this way we can see that placebo effect can work very well to support dubious non-evidence based health practices such as nutritional supplements (and I mean of the “wonder -food” variety) or other  dodgy and fake practices,; drinking sharks-fin soup (now thought toxic), rhino horn for increased potency, psychic surgery etc etc.

In scientific experimentation we frequently use controls such as inert substances (e.g. normal saline) and have to consider that is some cases these will produce an effect similar to what would be expected with an active substance (e.g. an IV analgesic). However we can counter this with large samples, double blind and repeat studies. Indeed, in scientific clinical trials we are required to take the placebo effect into account (a requirement was introduced in a revision of the Declaration of Helsinki )

A related phenomena is the nocebo (Latin for “to harm”) effect, which is basically the same as the placebo effect but this time  the subject experiences harmful, unpleasant, or undesirable effects after receiving a placebo. Nocebo responses are thought to be due only to the subject’s pessimistic belief and expectation that the inert drug will produce negative consequences. One well known example is that C. K. Meador claimed that people who believe in voodoo can actually die because of their belief (Meadow, 1992), and there are other studies that have demonstrated this effect.

Dr Costa suggests that these effects are neurological mediated by higher brain centres, and pain for example, is significantly affected by the higher brain, so it’s very open to the placebo/nocebo effects.

He also makes a good point about the ethical issues using placebos in research. Clearly research using nocebos has ethical problems but even with placebos is it ethical to deceive patients in this way for the sake of science (even if they know they “might” get a placebo)  or for physicians to give antibiotics for viral infections, and vitamins for fatigue (a common practice, even though it is not for the overall good of the population)?

So it seems there is lots of room for more research into this interesting phenomenon. We would be interested on what people think of the ethics of using placebos in both scientific research and practice.



Barnett, A. G., van der Pols, J. C., & Dobson, A. J. (2005). Regression to the mean: What it is and how to deal with it International Journal of Epidemiology, 34(1), 215-220. doi:10.1093/ije/dyh299

Meador C.K. (1992) Hex Death: Voodoo Magic or Persuasion?” Southern Medical Journal 85(3): 244-47).