The Placebo Effect Uses Fake Medicine to Get Real Results

When my daughter stubs her toe, we put a bandage on it and that helps. I just want to remark on how crazy that is. A bandage doesn’t contain medicine, it doesn’t provide cooling or heating to reduce inflammation or numb pain - and with a stubbed toe - a bandage can’t even perform its basic function of helping with a cut. But it still works; the toe feels better just because of a bandage. The reason this works is because of the placebo effect.

Placebos are, by definition, inert substances that do not have a physical effect on the body due to their ingredients. Typical placebos include a neutral saline solution or a sugar pill. In clinical trials, medications are compared to placebos because even without active ingredients, many patients experience relief or symptom reduction due to placebos alone. For decades, people assumed that relief from a placebo meant that the pain was “all in your head,” but placebos have been shown to impact a broad spectrum of diseases.^[1]

Before we step into how placebos work, we need to walk through some background information. The word placebo comes from Latin and originally meant “to please.” In the 1800s, the term was used to describe medicines prescribed to flatter or please a patient rather than to make them better.^[1] Since then, placebos have been used more widely than any other class of medication, as evidenced by the vast number of inert substances sold in the supplement market.^[1] Beginning in the 1950s, researchers measured the placebo effect and found it to be around 35% effective at reducing pain!^[1] The mechanism behind how placebos work is complex, incompletely understood, and differs depending on the condition being treated.^[1]

One factor of the placebo effect is psychological, based on behavior and emotions. All treatments come with social and physical cues, such as the size of a pill, the appearance of a clinic, the presence of a person in a white lab coat, and which Disney princess is on a bandage.^[2] These cues affect our expectations of how well a treatment will work, if it will hurt or not, and how we evaluate and interpret our symptoms.^[1,2,3,4] Placebos exploit this system by giving us psychological cues that help us reevaluate our suffering in a more beneficial way, lowering our symptoms.^[1,2,4]

The placebo effect goes beyond psychology. Studies have shown that placebos cause measurable chemical changes in the brain and body.^[2,3,4,5] When used to treat pain, placebos can stimulate the release of opioids, endorphins, endocannabinoids, and dopamine in the brain.^[2,5,6] Beyond pain, placebo use can alter hormone distribution throughout the body, modify immune system activity, and influence cardiovascular function.^[2] Studies have even found that long-term placebo use is associated with reduced mortality from heart disease.^[2] These real effects - let’s not forget - come from medications that by definition contain no active ingredient!

These features of placebos are what make medical clinical trials so amazing. Investigational medications must outperform all of the benefits of a placebo medication, and in fact, many medications don’t make it to market because overcoming these benefits is a tough challenge. Even more amazing, the drugs that do make it to market are even better than placebos. Although they still haven’t found a medication for stubbed toes that works better than a bandage with a little mermaid on it.

Creative Director Benton Lowey-Ball, BS, BFA

References:

[1] Beecher, H. K. (1955). The powerful placebo. Journal of the American Medical Association, 159(17), 1602-1606. https://jamanetwork.com/journals/jama/article-abstract/303530

[2] Wager, T. D., & Atlas, L. Y. (2015). The neuroscience of placebo effects: connecting context, learning and health. Nature Reviews Neuroscience, 16(7), 403-418. https://www.nature.com/articles/nrn3976

[3] Zunhammer, M., Spisák, T., Wager, T. D., & Bingel, U. (2021). Meta-analysis of neural systems underlying placebo analgesia from individual participant fMRI data. Nature communications, 12(1), 1391. https://www.nature.com/articles/s41467-021-21179-3

[4] Marchant, J. (2016). Placebos: honest fakery. Nature, 535(7611), S14-S15. https://www.nature.com/articles/535S14a

[5] Amanzio, M., & Benedetti, F. (1999). Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems. Journal of Neuroscience, 19(1), 484-494. https://www.jneurosci.org/content/19/1/484.short

[6] Chen, C., Niehaus, J. K., Dinc, F., Huang, K. L., Barnette, A. L., Tassou, A., ... & Scherrer, G. (2024). Neural circuit basis of placebo pain relief. Nature, 632(8027), 1092-1100. https://www.nature.com/articles/s41586-024-07816-z