How the Placebo Effect Works

One theory behind the placebo effect is thesubject-expectancy effect. When people already know what the result of taking a pill is supposed to be, they might unconsciously change their reaction to bring about that result, or simply report that result as the outcome even if it wasn't. Others believe that people who experience the placebo effect have becomeclassically conditionedto expect relief when they take medication. Remember Dr. Ivan Pavlov and the dog that salivated when it heard a bell? In the case of people and placebos, the stimulus is the medicine (or what's perceived to be medicine) and the response is relief from their symptoms.

The subject-expectancy effect and classical conditioning are pretty similar. In both, the patient has a built-in expectation of the outcome. The subject-expectancy effect, however, is subjective because it's based only on what the patient reports. But there have been measurable physical responses associated with taking a placebo, which lends strength to the classical conditioning theory.

In a 2002 study conducted by researchers at the UCLA Neuropsychiatric Institute, two groups of patients received experimentalantidepressants, while the third was given a placebo. After several weeks of taking pills, each group's brain activity was measured using electroencephalography (EEG). The patients who had been on the placebo and reported a positive effect showed a greater increase ofbrainactivity than those who had responded well to the drug. That activity was also centered in a different area of the brain, the prefrontal cortex [source:Leuchter]。The outcome of the UCLA study suggests that the brain isn't being "fooled" by a placebo after all -- it actually responds in a different way to a drug and a placebo.

Several recent studies have shown exactly how the brain responds to a placebo to decrease pain. One of the most groundbreaking was a 2004 study at the University of Michigan that demonstrated that the placebo effect is related to endorphins, the brain's own natural pain relievers [source:Zubieta]。In the study, healthy subjects were given a painful but harmless injection in the jaw while their brains were scanned by a PET scanner. The subjects were asked to rate theirpainlevel and the researchers injected more or less saline to keep the pain level at a consistent rate during the brain scan. The subjects were then given what they thought was a pain reliever, and all of them experienced a decrease in their pain levels after receiving the placebo. However, they also showed a change in brain activity in the brain's opioid receptors (which receive endorphins) and its areas related to processing and responding to pain. The expectation of pain relief caused the brain's pain relief system to activate.

Susceptibility to the placebo effect might be genetic. A December 2008 study conducted in at Uppsala University in Sweden tested a small group of people who had social anxiety disorder. After a treatment consisting of a placebo, all the subjects were tested for a variant of a gene called tryptophan hydroxylase-2, responsible for the manufacture of the neurotransmitter serotonin (which is related to regulating mood as well as a host of other functions). The majority of the subjects who responded well to the placebo had two copies of this particular gene variant, while those who didn't respond to the placebo didn't. A past study had shown that people with two copies of the gene variant had less anxiety [source:Fumark]。

Placebos not only have resulted in measurable effects in the brain, they've also been shown to relax muscles and nerves to bring pain and symptom relief to patients. So while the placebo effect is indeed in your head, it's not just psychological.

Placebos are often used in clinicaldrugtrials to determine how well a potential drug serves its intended purpose (known as itsefficacy）.安慰剂对照试验的基本设置nvolves two different groups of subjects: one that receives the experimental drug and one that receives a placebo (which can either be an inert substance or an active drug, depending on the trial). These trials are usuallydouble-blind-- meaning that neither the subjects nor the researchers know which group is receiving the experimental drug -- to avoid any potential bias. If researchers know that they're administering a placebo, they may convey doubts about its effectiveness to the subject.

If more subjects report a significantly better outcome with the drug than with the placebo, then the drug is generally considered a success (assuming it also meets other criteria, such as safety concerns). Placebos are most commonly employed when the experimental drug is one used fortreating mental illness. The placebo effect is considered especially strong when testing these kinds of drugs, so it can be more difficult to determine if an experimental drug is actually working better than one already in use.

Recently, some researchers have begun to question whether the standard placebo-controlled trial is an efficient way to test an experimental drug. If the placebo performs better than the drug, does it really mean that the drug is ineffective? Not everyone thinks so. Dr. Ted Kaptchuk states that, "Often, an active drug is not better than placebo in a standard trial, even when we can be confident that the active drug does work." The reverse can also be true. In one placebo-controlled trial, the drug performed better than the placebo, so ordinarily researchers would conclude that the drug, a painkiller, is effective. The researchers then administered the painkiller to another group of subjects without telling them what it was, expecting another positive result. It didn't work to relieve theirpainat all [source:Brooks]。其他研究已经表明,一些药物don't work as well when patients aren't told what they are or what they're supposed to do.

Some critics of the placebo-controlled trial state that they aren't really demonstrating a placebo effect, because many illnesses and diseases can resolve without any kind of treatment. They claim that it's wrong to attribute all positive outcomes to the placebo, and that in order to accurately measure the placebo effect in a clinical trial, you must have a third group of subjects that receive no treatment at all. However, some proponents of placebos believe that their effect can only be demonstrated in a healthcare setting, because subjects in clinical trials must be informed that they might receive a placebo.

Although doctors have been prescribing placebos for ages, they haven't talked about it very much. Only recently have researchers began to really study the clinical uses of placebos. The first survey of its kind was conducted by a medical student and a physician at the University of Chicago in late 2007. It showed that 45 percent of the about 200 doctors in Chicago-area hospitals had prescribed a placebo at some point in their medical practice. Nearly all the doctors believed that placebos had a therapeutic effect, even those who hadn't prescribed them [source:Sherman]。Another study conducted in October 2008 showed similar results. Half of the more than 600 doctors across the United States that responded to the survey said that they had prescribed placebos [source:Tilbert]。

Often, doctors prescribe placebos because they have no other form of relief to offer the patient. Either there is no effective medication available, or the patient can't take the commonly used medications due toside effectsor other reasons. For example, if a patient complains repeatedly of a symptom like fatigue, but the doctor can find no underlying cause for it, he or she might suggest that the patient take vitamins. Dr. Danielle Ofri described this scenario when she was interviewed about the 2008 survey. She said "I'll explain vitamins have worked for some of my patients, and there's no downside" [source:CNN]。Vitamins can certainly have benefits for some people, but there's probably not any definitive proof that they'll cure a patient's fatigue.

Doctors sometimes prescribe a placebo because the patient insists on taking some type of medication. Although it might sometimes be a case of simply giving the patient what he or she wants, doctors who prescribe placebos for this reason are more likely to decide that giving the patient nothing would be more harmful. One common example is the prescription ofantibioticswhen a patient has a cold or other illness caused by avirus. Antibiotics are only effective in treating bacterial infections, not viral ones, but many patients believe that they need an antibiotic anyway. Some doctors who prescribe them in these situations argue that the patient may end up having a bacterial infection anyway due to their weakened immune system. However, this practice seems to be less common as we learn more about antibiotic-resistant bacteria and the need to prescribe antibiotics only when absolutely necessary.

When a doctor prescribes a placebo, it's not usually a sugar pill. According to the surveys, the two most commonly prescribed placebos were over-the-counter pain pills likeaspirinand vitamins. Other doctors have prescribed antibiotics or sedatives. Critics argue that none of these are true placebos because they all contain ingredients that are active in some way, even if they aren't known to work for the patient's particular condition.

In 2006, the American Medical Association created a policy concerning placebos. It states that "physicians may use placebos for diagnosis or treatment only if the patient is informed of and agrees to its use" [source:AMA]。This is the biggest issue that critics raise: Doctors are essentiallylyingto their patients when they prescribe something that they know isn't proven to work for the patient's particular condition.

What if doctors strictly follow the AMA's guidelines? They would have to tell their patients that what they're being given doesn't actually contain medicine or isn't known to work for them. Some researchers believe that this would negate the placebo effect because of the psychological component. Others, especially those who believe that placebos work through classical conditioning, think that disclosing that the medication is really a placebo doesn't necessarily mean that it won't work.

Very few doctors are this open about prescribing placebos, but most of them don't outright lie to their patients, either. In general, doctors who prescribe placebos often say that they have something that they believe can help, but they don't know exactly how it will work, either. Supporters of the use of placebos point out that this isn't lying; placebos are known to be beneficial in some cases. The AMA policy suggests that doctors could explain the placebo effect to their patients and receive consent to prescribe them in the course of treating any illness. This way, the patients don't know exactly when they might be prescribed a placebo and they could still benefit from the placebo effect.

另一个问题我处方中固有的安慰剂s the fact that they haven't been shown to work on more than half of the population. If a doctor prescribes a placebo and it doesn't work, both doctor and patient are essentially back where they started in terms of trying to find a treatment. If the doctor continues to prescribe placebos, it may undermine the patient's trust and potentially diminish the therapeutic effect of any medication he prescribes in the future. In addition, the placebo effect is usually short-term -- placebos don't usually work for chronic conditions.

There's also a very real danger in prescribing drugs like sedatives andantibioticsas placebos. A sugar pill, a vitamin or anaspirinisn't generally likely to cause any problems. But drugs like sedatives and antibiotics could be doing more harm than good. Many sedatives are habit-forming, so the patient could develop a dependency on a drug that wasn't even supposed to work on his or her particular condition to begin with. Doctors who prescribe antibiotics when they're not absolutely necessary may also be contributing to the rise in strains of antibiotic-resistant bacteria such asMRSA.

The debate will continue to rage on concerning not only what constitutes a placebo, but whether doctors and researchers should continue to use them. Even some supporters of placebo use claim that it's such a loaded word that perhaps we should start using terms like "mind-body medicine" or "integrated healing" instead. But as long as many people believe that the placebo effect works, they're not likely to go away anytime soon.