The placebo effect plays a central role in doctors' understanding of whether medications work.
The effects of a placebo, or "dummy," treatment cannot come from the actual treatment itself. In other words, the placebo effect explains why people report feeling better when they think they are taking medicine, but aren't actually receiving the treatment. (The word placebo comes from the Latin for "I will please.")
The placebo effect can help explain why drugs and other treatments with no value can seem to work, and therefore, why some treatments pass muster while others do not.
However, the placebo effect itself remains mysterious. Doctors still have questions about how it operates, and why its effect can be large, small or nonexistent for a given treatment or patient.
The following pages share some of the history, knowledge and misconceptions about the placebo effect.
Early placebo research was done in the 18th century for consumer protection.
The first medical patent in the United States was issued in 1796 to a Connecticut physician named Elisha Perkins for metal "tractors," which the doctor claimed could cure sore joints and other pain when passed over an affected body part.
A number of physicians were skeptical that the expensive treatment actually did anything, and British doctor John Haygarth devised a test that compared the effectiveness of the tractors with similar devices fashioned out of entirely different materials, such as tobacco pipes and bone.
"Any benefit to the patient was psychological," wrote Simon Singh and Dr. Edzard Ernst in their book "Trick or Treatment" (Bantam Press, 2008). "Medicine had started its investigation into what we today would call the placebo effect."
Even real treatments benefit from the placebo effect.
In any clinical trial, researchers might determine that a drug is a certain percentage better than a placebo at treating people with a disease.
But this percentage is smaller than the difference between taking the drug and getting no treatment whatsoever. That's because patients who take a proven treatment get the benefits of both the treatment itself and the placebo effect.
"It's not an either/or. All the things that are going on when you take a placebo are also going on when you take a medication," said Aimee Hunter,an assistant professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA's David Geffen School of Medicine.
"Placebo" and "the placebo effect" refer to different things.
Placebos are, by definition, inactive drugs with no therapeutic benefit in and of themselves.
The placebo effect, meanwhile, can happen with any treatment, whether it has a demonstrated physical benefit or not, and refers to the effects of taking a medication that can't be attributed to the treatment itself.
There is a "nocebo" effect.
While the placebo effect might give patients a benefit beyond a treatment's actual physical effect, the nocebo effect (from the Latin for "I will harm") is its counterpart. The nocebo phenomenon refers unwanted side effects not actually due to the treatment itself.
In clinical trials, patients have been found to show side effects that did not come from the medication, researchers found.
This phenomenon is one of a number of reasons why doctors don't prescribe placebos when they don't have an effective medication to give.
Many clinical trials no longer include placebos.
Patients enrolling in a clinical trial may worry that instead of a possible treatment, they will be receiving a sham treatment, but that is often not the case.
When an effective treatment is available, it would generally be unethical for patients to be left untreated. In many trials, the alternative to the treatment being tested is not a placebo, but the current standard-of-care treatment.
In order for a new drug to be accepted as a treatment, researchers usually have to prove that the drug works better than the current standard-of-care treatment, for example, by alleviating symptoms better, for a longer time or with fewer side effects.
Placebos have a long-term, demonstrated effect in relieving pain.
Pain research has been a prime area of placebo investigations.
During World War II, Dr. Henry K. Beecher found that soldiers who believed they were getting morphine but instead received a salt-water solution still experienced relief. (This was done because supplies of morphine were low.) In a 1955 article in the Journal of the American Medical Association, Beecher outlined how placebos could be used to determine the effectiveness of medical treatments.
More recently, researchers have found that expectations of whether a pain drug will work or not play a significant role in whether a patient will get pain relief.
"I think it's fair to say the mechanisms of the placebo response are best known in pain," Hunter said. "Part of that is because the study of pain lends itself to experimental manipulation."
Scientists don't know if certain groups of people are more susceptible to placebos.
Because placebos relate to the power of suggestion, there has been a great deal of interest in finding whether certain groups of people are more susceptible to the placebo effect.
But while researchers have looked at age, gender and religiosity, among other factors, findings have been inconsistent.
"No one has been successful in identifying a profile of a placebo responder," Hunter said.
If such a group were found, she added, "drug companies would be excluding those people [from clinical trials], so they'd be able to test their drugs more correctly."
The placebo effect is actually several effects.
While it is referred to as the placebo effect (singular), there are actually multiple factors that determine how much a person might benefit beyond what a treatment can actually do.
For example, with antidepressants, the three components of patient expectations, classical conditioning and the relationship with the healthcare provider determine the extent of the placebo effect, Hunter said.
Classical conditioning, Hunter explained, is a physiologic response to being given a treatment over time, and is not necessarily a conscious reaction.
"How we respond to a medication depends in part on what we've been given before and how we've responded before," said Hunter. Even animals given an injection over the course of several days will continue to show a response to that medication, even if it is switched to a placebo, she said.
Psychiatric illnesses are among the conditions most susceptible to placebos.
"Psychiatric illness has among the highest rates of placebo response," Hunter said.
Anywhere from 30 to 50 percent of the people in a depression medication study will respond to placebo. This has made understanding the role of the placebo effect in depression treatment difficult.
Not all placebos are created equal.
Because some patients know what to expect with certain types of medication, researchers have sought ways to keep people from knowing whether they are being given a true treatment or not.
"Active placebos" do not do anything to treat the condition being studied, but they do cause some of the same side effects s the medication being tested, such as sleepiness. That way, patients don't know whether they are being given the drug being tested.
Because these active placebos do have some effect, however, ethical controversy surrounds their use.