Placebo Effect

What is a placebo?
A placebo (pluh-see-bow) is a substance or other kind of treatment that looks just like a regular treatment
or medicine, but its not. Its actually an inactive look-alike treatment or substance. This means its not a
medicine. The person getting a placebo does not know for sure that the treatment is not real. Sometimes
the placebo is in the form of a sugar pill, but a placebo can also be an injection, a liquid, or even a
procedure. Its designed to look like a real treatment, but doesnt directly affect the illness.
What is the placebo effect?
Even though they do not act on the disease, placebos seem to affect how people feel (this happens in up
to 1 out of 3 patients). A change in a persons symptoms as a result of getting a placebo is called
the placebo effect. Usually the term placebo effect speaks to the helpful effects a placebo has in
relieving symptoms. This effect usually lasts only a short time. Its thought to have something to do with
the bodys chemical ability to briefly relieve pain or certain other symptoms.
But sometimes the effect goes the other way, and causes unpleasant symptoms or worse. These may
include headaches, nervousness, nausea, or constipation, to name a few of the possible side effects.
The unpleasant effects that happen after getting a placebo are sometimes called the nocebo effect.
Together, these 2 types of outcomes are sometimes called expectation effects. This means that the
person taking the placebo may experience something along the lines of what he or she expects to
happen. If a person expects to feel better, that may happen. If the person believes that he or she is
getting a strong medicine, the placebo may be thought to cause the side effects. The placebo does not
cause any of these effects directly. Instead, the persons belief in or experience of the placebo helps
change the symptoms, or change the way the person perceives the symptoms.
Some patients can have the placebo effect without getting a pill, shot, or procedure. Some may just feel
better from visiting the doctor or doing something else they believe will help. That type of placebo effect
seems most related to the degree of confidence and faith the patient has in the doctor or activity.
How are placebos used?
Placebos may be used in clinical trials. Clinical trials are research studies testing new drugs or other
treatments in volunteers. Before a new treatment is used on people, its studied in the lab. If lab studies
suggest the treatment will work, the next step is to test it on animals. If that also gives promising results, it
may then be tested in clinical trials to see if it has value for patients. The main questions the researchers
want to answer are:
Does this treatment work?
Does it work better than what were now using?
What side effects does it cause?
Do the benefits of the treatment outweigh the risks?
Which patients are most likely to find this treatment helpful?
If standard treatments for the disease are already available, the new treatment is usually compared to
one of these treatments. This tells researchers if the new treatment is as good as or better than the one
thats currently available.
If theres no approved treatment for an illness or condition, some people in the study may be given a
placebo, while others get the new treatment being tested. The main reason to have a placebo group is to
be sure that any effects that happen are actually caused by the treatment and not some other factor.
The placebo looks, tastes, or feels just like the actual treatment, so that the patients and the doctors
expectations dont affect the outcomes. The placebo control makes it possible to blind patients and
doctors to what treatment theyre getting. In a double-blind controlled study, neither the volunteers taking
part in the study nor their doctors know whos getting which treatment. This study design helps avoid
biases in measuring outcomes that can be caused by the researchers or the patients expectations about
the treatment. This is not as big a problem in studies of cancer treatment, where objective outcome
measures are most often used. Its more likely in studies that require patient reporting for symptoms like
depression, sleeplessness, or pain.
If you would like to know more about clinical trials, see our document called Clinical Trials: What You
Need to Know.
People in a study that uses a placebo should always know that theres a chance they could be getting a
placebo. Its not OK to give someone a treatment in a clinical trial and not mention that it could be a
placebo. Please see our document Informed Consent for more information on this.
Those who get placebos in medical studies serve an important role. Their responses help provide a good
way to measure the actual effect of the treatment being tested. The placebo group provides an important
baseline with which to compare the treatment group. It helps researchers see what would have happened
without the treatment, though both groups may still have some short-term effects based on what the
patient expects. For instance, illnesses that sometimes go away on their own might be thought to get
better because of the medicine, unless theres a placebo group and those people get better too. On the
other side, bad effects that were going to happen anyway, or that occur from some unrelated cause, may
be blamed on the treatment unless they also happen to people in the placebo group.
How does the placebo effect work?
In the past, some researchers have questioned whether theres convincing proof that the placebo effect is
a real effect. But there are studies showing that the placebo effect is real. For example, scientists have
recorded brain activity in response to placebo. Since many scientific tests have shown the placebo effect,
its one way we know for sure that the mind and body are connected.
Some scientific evidence suggests that the placebo effect may be partly due to the release
of endorphins in the brain. Endorphins are the bodys natural pain killers. But theres probably more to it
than this.
Many think the placebo effect occurs because the patient believes in the substance, the treatment, or the
doctor. The patients thoughts and feelings somehow cause short-term physical changes in the brain or
body. The patient expects to feel better, and so he or she does feel better for some time. But even if a
person feels better after taking a placebo, it doesnt mean the persons illness or symptoms were not real.
For instance, the person may feel less anxious, so stress hormones drop. Taking a placebo may change
their perception for example, a person might re-interpret a sharp pain as uncomfortable tingling.
Whats commonly called the placebo effect even plays a role in mainstream medicine. Many people feel
better after they get medical treatments that they expect to work. But the opposite can also happen, and
this seems to support the idea of the expectation effect even more. For example, in one study, people
with Alzheimers disease got less relief from pain medicines. These patients required higher doses
possibly because they had forgotten they were getting the drugs, or they forgot that the pain medicines
had worked for them before.
This suggests that past experiences also play into the placebo effect. In one study that looked at the
placebo effect in pain relief, one group got a real pain medicine and the other did not. In the following
days, both groups were given a placebo that looked like the real pain medicine. Those who had gotten
the real pain medicine were able to tolerate more pain than those who had not gotten pain medicines
before.
In the same study, people who were given a drug that raised a certain hormone level beforehand actually
had a similar (but smaller) hormone response when they were given a placebo later. Those who had not
gotten the real drug beforehand had no change in their hormone levels when they got the placebo, even
though they were told that they would. This helped to separate the power of the researcher telling them
they would have an effect from the learned experience of having the effect in the past. This type of
learned response after personal experience is called theconditioning effect. It seems to be part of what
we call the placebo effect.
The nocebo effect, in which a person has more symptoms or side effects after a placebo, is still being
studied. Researchers believe it may be partly explained by a substance in the body that sends messages
through the nerves. When a person is anxious, for instance, the substance is activated and the person
feels more pain than a person who isnt anxious. The nocebo effect shows up in the brain: brain-imaging
studies have shown that pain is more intense when a person expects more pain than when they dont.
This is linked to changes in certain brain regions on the imaging studies.
Although we may not know exactly how it works, the idea that the mind can affect the body has been
around for thousands of years and is well-proven in certain situations. Many ancient cultures depended
on mind-body connections to treat illness. Shamans or medicine men would not have viewed their efforts
as placebos. But their healing powers may have worked partly through the patients strong belief that the
shamans treatments would restore health. Or it could be that a sick person was going to get better
anyway, but the recovery was thought to be because of the treatment which might have really done
nothing for the illness.
Because placebos often have an effect, even if the effect doesnt last long, some people think that the
placebo produced a cure. But placebos do not cure. And in studies where doctors are looking at whether
a tumor shrinks, placebos have very little, if any, effect.
Still, placebos clearly can help reduce certain symptoms such as pain, anxiety, and trouble sleeping in
some people. In earlier times, placebos were sometimes given by doctors out of frustration or
desperation, because nothing else was available or seemed to work. They might even be tried today a
2008 study found that nearly half of the doctors polled said that they used a placebo when they felt that it
might help the patient feel better.
Sometimes if the placebo looks more real, the person may think its an active medicine or treatment and
believe in its power even more. For example, a larger pill may look more powerful than a small pill. And in
some people, an injection may have a stronger placebo effect than a pill.
Some believe that placebos seem to work because many illnesses improve over time even without
treatment. People may also take better care of themselves by exercising, eating healthier, or resting if
they are taking a placebo. Just as natural endorphins may relieve pain once they are released, some
research shows the brain may respond to an imagined scene much as it would to something it actually
sees. A placebo may help the brain remember a time before the symptoms and bring about a chemical
change. This is a theory called remembered wellness.
Some scientists believe that the effects of many alternative therapies may simply be a placebo effect. If
the patient believes in the treatment and wants it to work, it can seem to do so, at least for a while. If this
effect worked on an illness that usually would not get better on its own, and it lasted, it would be
considered a real cure, not a placebo effect.
Finally, theres evidence to suggest that what a patient expects about real medicines can influence how
the patient feels after the medicine is taken. Even though responses from real drugs arent typically
thought of as placebo effects, some short-term effects are affected by expectations good ones as well
as bad.
Theres still much to find out about the placebo effect and all the ways it may work. Researchers agree
that the placebo effect cannot cure people or make them live substantially longer. Still, they continue to
study it in order to learn more about it, and find out whether and how it may be used to help people feel
better.
Other things that can add to or be confused for the placebo
effect
Certain other factors can affect study outcomes, and may be confused with the placebo effect. These are
effects that can cause a study to report that a placebo (or even a treatment) had some effect when in
reality, it didnt.
Timing of unrelated events
Along with the placebo or nocebo effect, incidental events (unrelated effects that might have happened
without the placebo) might also be linked to the placebo because of their timing. For example, a
headache or rash that happens soon after taking a placebo could be caused by something else entirely,
but the person might think the placebo caused it. The same can be said for good outcomes: if a person
happened to start feeling better after taking a placebo, that improvement may be thought to be due to the
placebo.
Healing or changes in symptoms
A health problem that improves on its own (many do) can sometimes add to whats thought of as the
placebo effect. Even in serious conditions such as cancer, some types appear to get better and worse on
their own, although they continue to spread and worsen over time. This is part of the effect of timing,
noted above. A person who was taking a placebo when symptoms started improving on their own is very
likely to believe that the placebo had some effect. And a self-limited illness that goes away completely on
its own at such a time might have the placebo-taker convinced it was a miracle drug.
Patient reporting
Lack of blinding can affect reporting of these kinds of coincidental timing effects and belief in what caused
them. For example, people who know theyre getting placebos will know that their headache is not due to
the medicine, and may not report it. Those who know they are getting the real medicine are more likely to
believe that the medicine is causing the headache, and are more likely to report it. Blinding helps to
balance these incidental timing effects.
Self-report of symptoms on a scale
Studies comparing placebo to no treatment found that patients were more likely to tell the study
investigator that there was some improvement in their comfort if they were on placebo. This was observed
when the patient had to rank their symptoms on a scale, say, from 1 to 10. When the patients rankings
were compared with outcomes others could measure (signs, like swelling or movement) there would be
no improvement in the measurable outcome. Some researchers believe this is due to patients wanting to
give the investigator good news. It may also be that the patient is comparing current symptoms to the
worst discomfort this problem had caused in the past.
Getting outside treatment
The patient who isnt getting better in a study may also seek outside medical help without mentioning it to
investigators. Or outside treatment for a related problem may help the symptom being studied in the
clinical trial. This can affect outcomes for both the placebo and treatment groups.
Study dropouts
People who are not getting better in the study, including those on placebo, are more likely to leave the
study before its over. This means that people who arent helped are less likely to be counted in the final
analysis. This makes any treatment look as if it works better than it does, because the people who felt
better during treatment were more likely to have their results counted at the end of the study than those
who didnt.