Author: Shweta Ramdas
Editors: Charles Lu, Whit Froehlich, and Scott Barolo

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Placebo or Nocebo?

Last year, when I pooh-poohed my mother’s alternative medicine regimen, she said, “But these actually work well for me, because I believe in them!” My mother had just outsmarted me with science.

The placebo effect is one of the most remarkable yet least understood phenomena in science. It is a favorable response of our body to a medically neutral treatment (sugar pills, anybody?): in other words, a placebo is a fake treatment that produces a very real response. This is attributed to a physical reaction stemming from a psychological response to the administration of therapy. You could say that a patient sometimes gets better anyway—how many times have we waited out the common cold—and you would be right. This natural return to the baseline which can happen is not considered the placebo effect, which is an improvement in response to a treatment.

Placebos were commonly used before the advent of modern medicine in the 20th century, when the priority of medicine was to comfort, rather than to cure (placebo in Latin means: “I shall please”). In modern medicine, about half of patients who participate in clinical trials are given dummy pills with no active ingredients (called controls). These patients may still respond positively to treatment, sometimes as well as the other group given the actual pill; this has even been seen in trials using drugs that are known to effectively treat the condition. This has been seen in illnesses as diverse as Parkinson’s disease, pain, asthma, and depression. On the other hand, placebos are half as effective as actual drugs at curing migraines. In extreme cases, which seem closer to science fiction than real science, placebo surgeries have been as effective in curing knee pain as actual surgeries. In fact, placebos sometimes work a little too well: they can also bring along with them the side-effects of the medicines they are supposed to mimic! This is called the “nocebo” effect (which in Latin means “I shall harm”).

Although placebos can provide symptomatic benefits to certain patients, they may also harm them by discouraging them from getting real treatment. This could be particularly dangerous for infectious diseases: while placebos may provide relief from symptoms (e.g. pain and depression), they rarely cure the underlying illness, leaving the patient capable of infecting others. This also affects patients suffering from diseases that require timely treatment, such as cancer or diabetes.

For a long time, it was thought that the placebo effect worked because of a belief in the cure. So…what happens when you know you’re being given the sugar pill? Does the placebo effect disappear? This question was studied because it is considered unethical for doctors to lie to their patients while prescribing placebos. Researchers tested whether patients who were told that they were being given a placebo showed more improvement than untreated patients. Surprisingly, they did!

The primary reason for the placebo effect is what is called the “expectancy effect.” When we see a doctor or take medicine, we have unconsciously learnt to expect to get better, to have our pain reduced, or to have our fever disappear. This expectation that arises from the ritual of medical care activates the body’s natural pain-killers or other healing mechanisms. This can either arise from a conscious expectation (“The doctor has given me a pill, thus I will get better”) or a conditioned response (you received a similar looking pill the last time you came to the doctor’s; you unconsciously expect the same result—getting better—this time around).

The magnitude of the placebo effect has strongly increased in the US over the last 20 years: by 2013, placebos were only 9% less effective than drugs at curing pain, compared to 26% in 1996. Researchers believe that this is because of direct-to-consumer advertising by medicine manufacturers. They bombard us into expecting that pills will work, whether or not they actually do!

Not everyone responds equally to the placebo effect. Are there biological factors that allow certain people to experience it? A group of researchers has shown that novelty-seeking and fun-seeking personality traits were associated with higher responsiveness to placebo treatments. These traits are linked to the brain’s reward pathway (also called the dopamine pathway), so it makes sense that they are also linked to the placebo effect, given that we know the reward pathway to be one mechanism by which the placebo effect works. And now, genetic factors are being linked to the placebo effect: variations in the gene COMT (again, surprise surprise, linked to the dopamine pathway) influenced patients’ responses to placebo treatment for inflammatory bowel disease.

The placebo effect is an intriguing phenomenon that shows that perception can influence medical symptoms. Belief, in itself, can be a powerful medicine. However, this power has limits. Ted Kaptchuk, a placebo researcher at Harvard, notes that placebos don’t shrink tumors, or make blind people see. Even in the case of asthma, they ameliorate symptoms rather than treating the actual condition. Similarly, antibiotics cannot be replaced by placebos.

But there is much that placebos can tell us about the mind-body connection, and about the larger ways social interactions and the environment can affect our bodies. And as we continue to learn about the biology underlying this phenomenon, I will cut my mother some slack for her esoteric regimens, but only as long as she still gets her annual check-up at the hospital.


About the author

shwetaShweta is a graduate student in Bioinformatics at the University of Michigan. Her research involves computational methods to understand the genetic basis of psychiatric disease. Her undergraduate degree is from the National University of Singapore where she studied computational biology. Outside of research, Shweta enjoys reading, yoga, and figuring out the genetic basis for being a muggle. Follow Shweta on Twitter.

Read all posts by Shweta here.


Image credit: Sierra Nishizaki 

2 thoughts on “Placebos: Tricking the Brain, Targeting the Body

  1. Very cool! I guess it’s not that surprising that a placebo effect has both a genetic basis as well as a learned or conditioned basis. So.. Can animals have the placebo effect? Does this have any broader implications for human evolution and the pressures that would select us for being good a deluding ourselves?


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