A placebo is a “fake” medicine or treatment intended to substitute for the real one, most commonly used for the control group in randomized trials. Placebos are not chemically or mechanically bioactive – they’re not supposed to have any actual physical effect on the body – but they can work on the mind. Any parent who has kissed a “boo boo” or reluctantly “wasted” a bandage on an unbroken patch of skin that hurts has seen the placebo effect in action. “Sham” procedures (“sham surgery” or “sham acupuncture”) are the placebo version of non-medication interventions. The opposite is the nocebo effect.
Deeper dive
Nearly all randomized controlled trials involve using a placebo, a biologically inactive substance (sometimes called a “sugar pill”) intended to appear like the actual medication or treatment that the participants in the real treatment group receive. A placebo should resemble the real treatment as much as possible so that participants do not know if they are receiving the real treatment or the “fake” one. Using placebos allows researchers to evaluate treatment effects above and beyond the “placebo effect,” the phenomenon in which a person feels better or experiences improvement of their condition based at least partly on the expectation that they will improve.
In a substantial number of people – estimated to be up to a third of all individuals – receiving a placebo for a condition improves their symptoms. Scientists do not fully understand all the mechanisms involved in the placebo effect, but the expectation of feeling better may activate the body’s endorphins, which relieve pain and can improve mood, similar to the way cursing and screaming have been shown to alleviate pain. The interaction with a doctor can also contribute to the placebo effect. Double-blind placebo-controlled trials ensure that neither the participant nor the researcher know which is the real treatment and which is placebo so that it’s less likely for those receiving placebo to know. If a medication in a trial leads to improvement, but that improvement is not statistically or clinically significant compared to the placebo, it calls into question whether it’s really the medication itself leading to improved outcomes or a mirrored placebo effect. This is also true with other interventions, even surgeries sometimes. In acupuncture trials, the control group should receive “sham” acupuncture, or needles in non-acupuncture locations, to adequately account for symptom improvements that may result from the placebo effect.
The lesser known nocebo effect describes a somewhat opposite phenomenon: a person experiences what they believe to be the side effects of the medication when they are actually taking a placebo, at least in part as a result of the expectation that they will experience side effects. Although it’s also been studied quite a bit, the nocebo effect has not been explored nearly as much as the placebo effect, or at least not until recently. Yet, just as the placebo effect can lead to great improvement in some people, the nocebo effect can actually be dangerous, almost leading to a fatality in one case study. The nocebo effect may relate to anxiety, and both placebo and nocebo effects have been observed in brain scan studies.
Not all improvements in symptoms in a control group are necessarily a result of a placebo effect: the American Cancer Society website discusses other phenomena that can be confused with the placebo effect. Also discussed in detail at the ACS website, placebos can be used to answer the following questions in research:
- Does this treatment work?
- Does it work better than what we’re 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?