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What is a Placebo

Medically reviewed on Feb 10, 2013 by L. Anderson, PharmD.

A placebo (or dummy pill) is an inert substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. For example, placebo pills or liquids may contain starch, sugar, or saline. Physical placebo, or “sham” treatments have also been used, such as inactive acupuncture devices.

Placebos are often used in clinical trials as an inactive control so that researchers can better evaluate the true overall effect of the experimental drug treatment under study. In these clinical trials, one subset of patients would receive the placebo and one group would receive the experimental drug, but neither group is aware of which treatment they have received. In addition, researchers in the study would not know which patients have received active or placebo treatments. These studies are called “double-blind” and “placebo-controlled” and are considered the gold standard for experimental drug research. However, unexpected high placebo rates in clinical trials can be detrimental, undermining the true effect of an active treatment.1

Conducting a double-blind, placebo-controlled clinical trial helps to eliminate any bias that might occur due to knowledge of who receives which treatments. A patient or researcher would expect those who receive the active drug to have a better outcome than those who did not, and this knowledge can introduce bias into the study. Typically, an experimental drug treatment needs to be statistically more effective than the placebo to be considered as a valid drug treatment. Including a placebo group in a study is also beneficial in evaluating treatment side effects. However, many clinical trials, such as those in cancer research, do not include placebo groups because it would not be ethical to leave the patient’s cancer untreated. In these trials, the experimental drug may be compared to a treatment that is already FDA-approved instead of a placebo. High placebo rates in clinical trials can also be detrimental, undermining the true effect of an active treatment.1

What is the placebo effect? What is a nocebo effect?

Research has shown that a placebo treatment can have a positive therapeutic effect in a patient, even though the pill or treatment is not active. This is known as the “placebo effect” or “placebo response”.

Placebo effects have been reported to occur in 21 to 40 percent of patients depending upon the study type.1 For example, in pain studies utilizing brain imaging, it has been shown that administration of a placebo to patients who believed they were receiving an analgesic medication led to activation of the endogenous opioid system in the brain. Endogenous opioids, such as endorphins and enkephalins, are natural pain-relieving chemicals produced in the body. Analgesia due to the placebo effect is dependent upon the activation of theses endogenous opioids in the brain. It has also been shown that the placebo response in patients with post-operative pain could be blocked by the opiate antagonist naloxone, further lending support to the placebo effect.2 Dopamine, another central nervous system neurotransmitter, has also been shown to be activated in the brain after placebo administration to patients with Parkinson’s disease.2

A 2010 Cochrane Review of 202 trials comparing placebo treatment with no treatment reported that placebos produced no major health benefits, but did have a modest effect on patient-reported outcomes, such as in pain and nausea, although results were variable. The authors explained that the observed variations in the placebo effect of placebo could be explained by trial design differences and how patients were informed of their treatments.3

A nocebo effect is the opposite of the placebo effect - a negative psychological effect of a treatment with no pharmacologic activity. This can occur when the placebo is administered and accompanied by the suggestion that the patients ailment will get worse. High nocebo effects can also interfere with interpretation of clinical trial results. Negative effects of drugs may be due to psychological nocebo effects and not necessarily due to the drug itself.1

It is ethical to use a placebo in medical treatment?

In clinical practice, physicians may prescribe placebo treatments with or without the patients knowledge that they are receiving an inactive therapy. Psychologically, the patient may be encouraged that they are receiving a treatment for their ailment that they believe will have beneficial effect, and in turn the placebo may actually provide some relief. However, the effect would not be due to a pharmacological action attributed to the chemical composition of the medicine. Placebos have been used in treatment of sleep, anxiety, gastrointestinal disorders, chronic pain and other disorders. The therapeutic use of placebo or sham treatments in medicine is very controversial.

In one survey, only three percent of U.S. physicians reported using actual sugar pills as placebos, but 41 percent said they had used over-the-counter painkillers and 38 percent said they had used vitamins as placebos for their patients. Sixty-eight percent of physicians described the placebo to their patients as a potentially beneficial medicine, and roughly two-thirds of the doctors felt the practice was ethical.4

In another study, physicians used reduced doses of anti-inflammatory medications mixed in combination with a placebo to successfully treat psoriasis patients. Combining active drug with placebo may be effective in diseases that involve the mental state and immune system, including asthma, multiple sclerosis, and chronic pain. Reducing doses by combining with placebo treatment could also reduce side effects, addiction potential and cost.

See Also


1. Enck P, Benedetii F, Schedlowski M, et al. New insights into the placebo and nocebo responses. Neuron 2008;59:195-206.

2. Meissner K, Kohls N, Colloca L. Introduction to placebo effects in medicine: mechanisms and clinical implications. Phil. Trans. R. Soc. B. 2011;366:1783-9.

3. Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database of Systemic Review 2010, Issue 1. Art No: CD003974. DOI: 10.1002/14651858.CD003974.pub3. Accessed online 10/7/2011.

4. Tilburt J, Emanuel E, Kaptchuk T, et al. Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ 2008;337:a1938. Accessed online 10/7/2011.