In medicine, a placebo is a substance, pill, or other treatment that appears to be a medical intervention, but isn’t one. Placebos are particularly important in clinical trials, during which they’re often given to participants in the control group.

Because a placebo isn’t an active treatment, it shouldn’t have a significant effect on the condition. Researchers can compare the results from the placebo to those from the actual drug. This helps them to determine if the new drug is effective.

You may be familiar with the term “placebo” in reference to something called the placebo effect. The placebo effect is when an improvement is observed, despite an individual receiving a placebo as opposed to active medical treatment.

It’s estimated that 1 in 3 people experience the placebo effect. Keep reading to learn more about the placebo effect, how it may work, and some examples from research.

The placebo effect represents a fascinating connection between mind and body that still isn’t completely understood. Below, we’ll discuss some psychological explanations for the placebo effect.

Classical conditioning

Classical conditioning is a type of learning. It happens when you associate a thing with a specific response. For example, if you get sick after eating a specific food, you may associate that food with having been sick and avoid it in the future.

Because the associations learned through classical conditioning can affect behavior, they may play a role in the placebo effect. Let’s look at a couple of examples:

  • If you take a specific pill for headaches, you may begin to associate that pill with pain relief. If you receive a similar-looking placebo pill for a headache, you may still report decreased pain due to this association.
  • You may associate the doctor’s office with receiving treatment or feeling better. This association can then in turn influence how you feel about the treatment you’re receiving.

Expectations

The placebo effect has a large root in a person’s expectations. If you have prior expectations for something, they can influence your perception of it. Therefore, if you expect a pill to make you feel better, you may feel better after taking it.

You can generate expectations for improvement from many types of cues. Some examples include:

  • Verbal. A doctor or nurse may tell you that a pill will be effective at treating your condition.
  • Actions. You may feel better when you’ve actively done something to address your condition, such as take a pill or receive an injection.
  • Social. Your doctor’s tone of voice, body language, and eye contact can be reassuring, making you feel more positive about the treatment.

The nocebo effect

It’s important to note that not all placebo effects are beneficial. In some cases, symptoms may worsen instead of improve when receiving a placebo.

This is called the nocebo effect. The mechanisms of the placebo and nocebo effect are believed to be similar, with both involving things like conditioning and expectations.

Below, we’ll explore three examples of the placebo effect from real studies.

Migraine

A 2014 study assessed how the labeling of drugs affected episodic migraine in 66 people. This is how the study was set up:

  1. Participants were asked to take a pill for six different migraine episodes. During these episodes, they were given either a placebo or a migraine medication called Maxalt.
  2. The labeling of the pills was varied throughout the study. They could be labeled as placebo, Maxalt, or either type (neutral).
  3. Participants were asked to rate pain intensity 30 minutes into the migraine episode, take their assigned pill, and then rate pain intensity 2.5 hours later.

Researchers found that the expectations set by the pill labeling (placebo, Maxalt, or neutral) had an effect on the pain intensity reported. Here are the results:

  • As expected, Maxalt provided more relief than placebo. However, placebo pills were observed to provide more relief than a no treatment control.
  • Labeling mattered! For both Maxalt and placebo, the rating of relief was ordered based off of labeling. In both groups, pills labeled as Maxalt were highest, neutral was in the middle, and placebo was lowest.
  • This effect was so strong that Maxalt labeled as a placebo was rated to provide about the same amount of relief as a placebo that was labeled as Maxalt.

Cancer-related fatigue

Fatigue may still be a lingering symptom in some cancer survivors. A 2018 study looked at the effects of a placebo compared to treatment as usual in 74 cancer survivors with fatigue. The study was set up as follows:

  1. For 3 weeks, participants either received a pill openly labeled as a placebo or received their treatment as usual.
  2. After the 3 weeks, people taking the placebo pills stopped taking them. Meanwhile, those receiving usual treatment had an option to take the placebo pills for 3 weeks.

After the study concluded, the researchers observed that the placebo, despite being labeled as such, had an effect on both groups of participants. The results were:

  • After 3 weeks, the placebo group reported improved symptoms compared to those receiving treatment as usual. They also continued to report improved symptoms over 3 weeks after discontinuation.
  • People receiving treatment as usual that decided to take the placebo pill for 3 weeks also reported an improvement in their fatigue symptoms after 3 weeks.

Depression

A 2015 study investigated the placebo effect in 35 people with depression. Participants weren’t currently taking any other medications for depression at the time. The study was set up like this:

  1. Each participant received placebo pills. However, some were labeled as a fast-acting antidepressant (the active placebo) while others were labeled as a placebo (the inactive placebo). Each group took the pills for a week.
  2. At the end of the week, a PET scan measured brain activity. During the scan, the active placebo group got a placebo injection, being told that it may improve their mood. The inactive placebo group received no injection.
  3. The two groups switched pill types for another week. A second PET scan performed at the end of the week.
  4. All participants then received treatment with antidepressant medications for 10 weeks.

Researchers found that some individuals experienced the placebo effect and that this effect impacted their brain activity and response to antidepressants. The results were that:

  • A decrease in depression symptoms was reported when people were taking the active placebo.
  • Taking the active placebo (including the placebo injection) was associated with PET scans that showed increases in brain activity in areas associated with emotion and stress regulation.
  • People who experienced increased brain activity in this area often had an improved response to the antidepressants used at the end of the study.

While the placebo effect has been observed in many scenarios, there’s still a lot about it that we don’t understand. Studies are ongoing and we learn more every year.

One of the big questions is the connection between mind and body. How are psychological factors like expectations affecting what’s going on inside us?

We know that the placebo effect can lead to the release of various small molecules like neurotransmitters and hormones. These can then interact with other parts of the body to cause changes. However, we still need to work out more details about the specifics of these complex interactions.

Additionally, the placebo effect seems to have a significant impact on some symptoms, such as pain or depression, and not others. This brings up more questions.

Ongoing questions about the placebo effect

  • Which symptoms are affected by the placebo effect? If so, what’s the magnitude of the effect?
  • Is using a placebo for these symptoms as effective or more effective than using medications?
  • The placebo effect can improve some symptoms but isn’t a cure. Is it ethical to use a placebo instead of a medication?

A placebo is a pill, injection, or thing that appears to be a medical treatment, but isn’t. An example of a placebo would be a sugar pill that’s used in a control group during a clinical trial.

The placebo effect is when an improvement of symptoms is observed, despite using a nonactive treatment. It’s believed to occur due to psychological factors like expectations or classical conditioning.

Research has found that the placebo effect can ease things like pain, fatigue, or depression. However, we still don’t know the exact mechanisms in the body that are contributing to this effect. Scientists are currently working to answer this question and more.