What is the Difference Between Placebo and Nocebo

Placebo and nocebo are very common in clinical trials. The nocebo effect is usually the opposite of the placebo effect.

The key difference between placebo and nocebo is their effect. Placebo is an inert substance that provokes perceived benefits in patients during medical treatments, while nocebo is an inert substance that causes perceived harm in patients during medical treatments.

CONTENTS

1. Overview and Key Difference
2. What is Placebo 
3. What is Nocebo
4. Similarities – Placebo and Nocebo
5. Placebo vs Nocebo in Tabular Form
6. Summary – Placebo vs Nocebo
7. FAQ – Placebo and Nocebo

What is Placebo?

Placebo is an inactive treatment or procedure designed to mimic a therapy but has no therapeutic effect and results in positive benefits in patients. Placebo is a sham medication.  Mostly weakened sugars with no biological effect are used as placebos. The placebo effect is when a person experiences improvement from a treatment, even if the treatment is inactive or neutral, due to their belief in its effectiveness. Moreover, the causes of the placebo effect may include hormonal response, classical conditioning, expectations (verbal, behavioral, social cues), and genetics.

Figure 01: Placebo

Placebos can have a positive effect on conditions such as depression, pain, sleep disorders, irritable bowel syndrome, and menopause. Placebo also reduces anxiety. Furthermore, the advantage of using a placebo when evaluating a new drug is that it weakens or eliminates the effect that expectations can have on the outcome.

What is Nocebo?

Nocebo is a harmless medication, procedure, or vaccine that causes harmful effects in a patient due to a patient’s negative expectations or beliefs about it. The nocebo effect occurs when negative expectations of a treatment, even if the treatment is harmless, lead to negative effects. The nocebo effect can be caused by factors such as healthcare beliefs, verbal or written health advice, media, the internet, social modeling, cost, patient expectations, and past experience with treatment.

Figure 02: Nocebo

Furthermore, the nocebo effect can cause a wide range of symptoms, including drowsiness, nausea, dizziness, difficulty concentrating, headache, insomnia, fatigue, itching, bloating, stomach pain, and loss of appetite.

Similarities Between Placebo and Nocebo

1. Placebo and nocebo are inert substances or sham medications.
2. They are common in clinical trials.
3. Their effects are mainly due to the psychological perceptions of patients.
4. Their effects can be seen in medical research as well as in psychological research.

Difference Between Placebo and Nocebo

Definition

1. A placebo is any inert substance or treatment that has no active properties reported to have an improvement in symptoms in patients.
2. A nocebo is an inert substance or sham medication that provokes negative harm in patients during medical treatment.

Causes

1. Placebo effects can be caused by hormonal response, classical conditioning, expectation, and genetics.
2. Nocebo effects can be caused by healthcare beliefs, verbal or written health advice, media, the internet, social modelling, how doctors and nurses talk about the effects of treatment, cost, patient expectations, and past experience.

Benefits or Harmful Effects

1. Placebos improve symptoms of depression, pain, sleep disorders, irritable bowel syndrome, and menopause, reduce anxiety, and weaken or eliminate the effect that expectations can have on the outcome when testing a new drug.
2. Nocebo causes or worsens symptoms such as drowsiness, nausea, dizziness, difficulty concentrating, headache, insomnia, fatigue, itching, bloating, stomach pains, loss of appetite, sensory changes, and mood changes.

The following table summarizes the difference between placebo and nocebo.

Summary – Placebo vs Nocebo

Clinical trials are prospective biomedical or behavioral research studies that incorporate human participants. Both placebo and nocebo are inert substances or sham medications that are used in clinical trials. Both placebo and nocebo effects can be potent and should be understood by both doctors and researchers for proper application in medicine. Placebo is an inert substance or sham medication that provokes positive benefits in patients during medical treatment, while nocebo is an inert substance or sham medication that provokes negative harm in patients during medical treatment. This summarizes the difference between placebo and nocebo.

FAQ: Placebo and Nocebo

1. Who invented the placebo?

• Henry Beecher discovered the placebo effect for the first time during World War II. After running out of pain-killing morphine, Henry Beecher replaced it with a simple saline solution. But he continued to tell the wounded soldiers it was morphine to calm them.

2. What is an example of a placebo effect?

• In research, all the patients are given what they believe to be medication to help/get rid of their nausea, but only about half of them get the actual medication, and the rest of the half get inert substances or sugar pills. The placebo effect occurring in this research could be the inert substances reducing nausea symptoms in patients.

3. Is placebo a fake drug?

• A placebo is anything that seems to be a “real” medical treatment but is not real. It could be a pill, a shot, or some other type of “fake” treatment or sham treatment.

4. Is placebo harmful?

• A negative side effect due to a placebo is called the nocebo effect. If people tell someone that they develop diarrhea after taking the placebo pill, then it results in the nocebo effect. The expectation may cause some people to experience this effect.

5. What are examples of nocebo effects?

• If patients think a treatment will be painful, there’s a higher chance that they will experience pain. Even a belief about possible side effects can cause side effects, from muscle spasms to chest pain

Reference:

1. Kendra Cherry, MSEd. “How Does the Placebo Effect Work?” Verywell Mind, Verywell Mind.
2. Raypole, Crystal. “Nocebo Effect: When Negative Thinking Impacts Health.” Healthline, Healthline Media.

Image Courtesy:

1. “Cebocap” By NIH, objects donated by Elaine and Arthur Shapiro – (Public Domain) via Commons Wikimedia
2. “Nocebo WikiWorld” By I, Greg Williams (CC BY-SA 3.0) via Commons Wikimedia

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