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What Is the Placebo Effect? | Definition & Examples

Published on October 16, 2022 by Kassiani Nikolopoulou . Revised on March 6, 2023.

The placebo effect is a phenomenon where people report real improvement after taking a fake or nonexistent treatment, called a placebo . Because the placebo can’t actually cure any condition, any beneficial effects reported are due to a person’s belief or expectation that their condition is being treated.

The placebo effect is often observed in experimental designs where participants are randomly assigned to either a control or treatment group. 

Table of contents

What is a placebo, what is the definition of placebo effect, how does the placebo effect work, placebo effect examples, downside of the placebo effect, other types of research bias, frequently asked questions about the placebo effect.

A placebo can be a sugar pill, a salt water injection, or even a fake surgical procedure. In other words, a placebo has no therapeutic properties . Placebos are often used in medical research and clinical trials to help scientists evaluate the effects of new medications.

In these clinical trials, participants are randomly assigned to either the placebo or the experimental medication. Crucially, they are not aware of which treatment they receive. The results of the two groups are compared, to see whether they differ.

In double-blind studies , researchers also don’t know who received the actual treatment or the placebo. This is to prevent them from conveying demand characteristics to participants that could influence the study’s results. This is preferred over single-blind studies, where participants do not know which group they have been placed in, but researchers do.

Placebos may help relieve symptoms like pain, fatigue, or stress-related insomnia, but they don’t actually treat a condition or cure a disease. Note that due to ethical considerations , placebos are not always used in clinical trials. For example, as it would be unethical to leave terminal cancer patients untreated, placebos aren’t used in these types of studies.

For some people, just the idea that they are taking medication makes them feel better. This occurs even if the medication is actually just a placebo. This phenomenon is known as the placebo effect . In other words, the perception of feeling better is triggered by the person’s belief in the benefit of the treatment.

When studying a new treatment, researchers must demonstrate that it is more effective than can just be explained by the placebo effect. To do so, they compare the results from those taking the new treatment with those from the placebo. In order to accurately compare the two groups, participants in clinical trials must not know whether they received the treatment or the placebo. If the two groups have the same reaction, the effectiveness of the new treatment is not supported.

Although the exact reasons for the positive effects of placebos are still being researched, a number of factors contribute to the phenomenon. These include:

• A person’s expectations or beliefs that they will get better . People who are motivated and expect their treatment to work are more likely to experience the placebo effect.
• The feeling of receiving attention and care due to participation in the study. This may reduce stress levels and trigger the body’s own pain-relieving chemicals.
• Classical conditioning , or the association people build over the years between a certain action, such as pill-taking, and positive results.
• A trusting relationship between doctors and patients or researchers and study participants from the sample . Listening to an expert you trust talk enthusiastically about a treatment can impact how you respond to it.

However, researchers do not attribute the placebo effect exclusively to psychology. A few other possible explanations include:

• Regression to the mean: When people first visit a doctor or start on a clinical trial, their symptoms might be particularly bad. But in the natural course of an illness, symptoms may subside on their own.
• Confirmation bias : Feelings of hopefulness about a new treatment may lead people to pay more attention to signs that they’re getting better and less attention to signs that they’re getting worse.

The placebo effect illustrates how the mind can trigger changes in the body.

After participants take the pill, their blood pressure and pulse rate increases, and their reaction speeds are improved.

However, when the same people are given the same pill and told it will help them relax and sleep, they report experiencing relaxation instead.

The placebo effect can also explain the popularity of non-FDA-approved products.

Evidence from published studies show that it takes extremely high doses for CBD to be effective. Documented benefits of CBD in placebo-control trials require anywhere from hundreds to thousands of milligrams per day. This is the equivalent of taking almost an entire bottle each day, depending on the concentration.

Most people take 15 milligrams or less per day, far less than what the studies deem an effective dose. The placebo effect seems to play a role here: the expectation is so high that people start to believe it’s working.

The response of people assigned to the placebo control group may not always be positive. They may experience what is called a “nocebo effect,” or a negative outcome, when taking a placebo. The same explanation applies here. If you expect a negative outcome, it’s more likely you’ll have a negative outcome.

For example, in a clinical trial, participants who are given a placebo but are told what side effects the “treatment” may cause. They may have the same side effects as the participants who are given the active treatment, only because they expect them to occur.

Cognitive bias

• Confirmation bias
• Baader–Meinhof phenomenon
• Availability heuristic
• Halo effect
• Framing effect
• Optimism bias
• Negativity bias
• Affect heuristic
• Representativeness heuristic
• Anchoring heuristic
• Primacy bias

Selection bias

• Sampling bias
• Ascertainment bias
• Attrition bias
• Self-selection bias
• Survivorship bias
• Nonresponse bias
• Undercoverage bias
• Hawthorne effect
• Observer bias
• Omitted variable bias
• Publication bias
• Pygmalion effect
• Recall bias
• Social desirability bias
• Placebo effect
• Actor-observer bias
• Ceiling effect
• Ecological fallacy
• Affinity bias

Although there is no definite answer to what causes the placebo effect , researchers propose a number of explanations such as the power of suggestion, doctor-patient interaction, classical conditioning, etc.

Placebos are used in medical research for new medication or therapies, called clinical trials. In these trials some people are given a placebo, while others are given the new medication being tested.

The purpose is to determine how effective the new medication is: if it benefits people beyond a predefined threshold as compared to the placebo, it’s considered effective and not the result of a placebo effect .

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Controlling for the Placebo Effect

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The Placebo Effect: Fake Treatment, Real Response

Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

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The mind can trick you into believing that a fake treatment has real therapeutic results, a phenomenon known as the placebo effect. In some cases, placebos can exert an influence powerful enough to mimic the effects of real medical treatments.

In this phenomenon, some people experience a benefit after the administration of an inactive lookalike substance or treatment. This substance, or placebo, has no known medical effect and can be in the form of a pill (sugar pill), injection (saline solution), or consumable liquid.

In most cases, the person does not know that the treatment they're receiving is actually a placebo. Instead, they believe they've received the real treatment. The placebo is designed to seem exactly like the real treatment, yet the substance has no actual effect on the condition it purports to treat.

The placebo effect is much more than just positive thinking , however. When this occurs, many people have no idea they are responding to what is essentially a sugar pill. Placebos are often used in medical research to help doctors and scientists discover and understand the physiological and psychological effects of new medications.

Here's why the placebo effect is important, how it happens, and why it works.

Placebo vs. Placebo Effect

It is important to note that a "placebo" and the "placebo effect" are different things. The term placebo refers to the inactive substance itself, while the term placebo effect refers to any effects of taking a medicine that cannot be attributed to the treatment itself.

Causes of the Placebo Effect

Although researchers know that the placebo effect is real, they do not yet fully understand how and why it occurs. Various factors might contribute to this phenomenon.

Hormonal Response

One possible explanation is that taking the placebo triggers a release of endorphins. Endorphins have a structure similar to that of morphine and other opiate painkillers and act as the brain's own natural painkillers.

Researchers have demonstrated the placebo effect in action using brain scans, showing that areas with many  opiate  receptors were activated in both the placebo and treatment groups. Naloxone is an opioid antagonist that blocks both natural endorphins and opioid drugs. After people received naloxone, placebo pain relief was reduced.

Conditioning

Other possible explanations include classical conditioning , or when you form an association between two stimuli resulting in a learned response. In some cases, a placebo can be paired with an actual treatment until it evokes the desired effect.  

For example, if you're regularly given the same arthritis pill to relieve stiff, sore joints, you may begin to associate that pill with pain relief. If you're given a placebo that looks similar to your arthritis pill, you may still believe it provides pain relief because you've been conditioned to do so.

Expectation

Expectations, or what we believe we will experience, have been found to play a significant role in the placebo effect. People who are highly motivated and expect the treatment to work may be more likely to experience a placebo effect.

A prescribing physician's enthusiasm for treatment can even impact how a patient responds. If a doctor seems very positive that a treatment will have a desirable effect, a patient may be more likely to see benefits from taking the drug. This demonstrates that the placebo effect can even take place when a patient is taking real medications to treat an illness.

Verbal, behavioral, and social cues can contribute to a person's expectations of whether the medication will have an effect.

• Behavioral : The act of taking a pill or receiving an injection to improve your condition
• Social : Reassuring body language, eye contact, and speech from a doctor or nurse
• Verbal : Listing to a health care provider talk positively about treatment

Genes may also influence how people respond to placebo treatments. Some people are genetically predisposed to respond more to placebos. One study found that people with a gene variant that codes for higher levels of the brain chemical dopamine are more prone to the placebo effect than those with the low-dopamine version. People with the high-dopamine version of this gene also tend to have higher levels of pain perception and reward-seeking.

The Nocebo Effect

Conversely, individuals can experience more symptoms or side effects as a response to a placebo, a response that is sometimes referred to as the " nocebo effect ." For example, a patient might report having headaches, nausea, or dizziness in response to a placebo.

The placebo effect can be used in a variety of ways, including in medical research and psychology research to learn more about the physiological and psychological effects of new medications.

In Medical Research

In medical research, some people in a study may be given a placebo, while others get the new treatment being tested. The purpose of doing this is to determine the effectiveness of the new treatment. If participants taking the actual drug demonstrate a significant improvement over those taking the placebo, the study can help support the claim for the drug's effectiveness.

When testing new medications or therapies, scientists want to know if the new treatment works and if it's better than what's already available. Through their research, they learn the sort of side effects the new treatment might produce, which patients may benefit the most, and if the potential benefits outweigh the risks.

By comparing the effects of a treatment to a placebo, researchers hope to be able to determine if the effects of the medicine are due to the treatment itself or caused by some other variable.

In Psychology Experiments

In a psychology experiment, a placebo is an inert treatment or substance that has no known effects. Researchers might utilize a placebo control group , which is a group of participants who are exposed to the placebo or fake independent variable . The impact of this placebo treatment is then compared to the results of the  experimental group .

Even though placebos contain no real treatment, researchers have found they can have a variety of both physical and psychological effects. Participants in placebo groups have displayed changes in heart rate, blood pressure, anxiety levels, pain perception, fatigue, and even brain activity. These effects point to the brain's role in health and well-being.

Benefits of Using a Placebo

The major 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. If researchers expect a certain result, they may unknowingly give clues to participants about how they should behave. This can affect the results of the study.

To minimize this, researchers sometimes conduct what is known as a double-blind study . In this type of study, neither the study participants nor the researchers know who is getting the placebo and who is getting the real treatment. By minimizing the risk of these subtle biases influencing the study, researchers are better able to look at the effects of the drug and the placebo.

One of the most studied and strongest placebo effects is in the reduction of pain. According to some estimates, approximately 30% to 60% of people will feel that their pain has diminished after taking a placebo pill.

For example, imagine that a participant has volunteered for a study to determine the effectiveness of a new headache drug. After taking the drug, she finds that her headache quickly dissipates, and she feels much better. However, she later learns that she was in the placebo group and that the drug she was given was just a sugar pill.

Placebo Effect Outcomes

While placebos can affect how a person feels, studies suggest that they do not have a significant impact on underlying illnesses. A major review of more than 150 clinical trials involving placebos found that placebos had no major clinical effects on illnesses. Instead, the placebo effect had a small influence on patient-reported outcomes, particularly of perceptions of nausea and pain.

However, another review conducted nearly 10 years later found that in similar populations, both placebos and treatments had similar effects. The authors concluded that placebos, when used appropriately, could potentially benefit patients as part of a therapeutic plan.

• Depression : The placebo effect has been found to impact people with major depression disorder. In one study, participants who weren’t currently taking any other medication were given placebo pills labeled as either fast-acting antidepressants or placebo for one week. After the week, the researchers took PET scans and told the participants they were receiving an injection to improve mood. Participants who took the placebo labeled as an antidepressant as well as the injection reported decreased depression symptoms and increased brain activity in areas of the brain linked to emotion and stress regulation.
• Pain management : A small 2014 study tested the placebo effect on 66 people with episodic migraine, who were asked to take an assigned pill—either a placebo or Maxalt (rizatriptan), which is a known migraine medication—and rate their pain intensity. Some people were told the pill was a placebo, some were told it was Maxalt, and others were told it could be either. Researchers found that the expectations set by the pill labeling influenced the participants responses. Even when Maxalt was labeled as a placebo, participants gave it the same rating as a placebo that was labeled Maxalt.
• Symptom relief : The placebo effect has also been studied on cancer survivors who experience cancer-related fatigue. Participants received three weeks of treatment, either their regular treatment or a pill labeled as a placebo. The study found that the placebo (despite being labeled as such) was reported to improve symptoms while taking the medication and three weeks after discontinuation.

A Word From Verywell

The placebo effect can have a powerful influence on how people feel, but it is important to remember that they are not a cure for an underlying condition.

Healthcare providers aren't allowed to use placebos in actual practice without informing patients (this would be considered unethical care), which reduces or eliminates the desired placebo effect.

However, by using placebos in research, during which they don't have to inform the participant, scientists are able to get a better idea of how treatments impact patients and whether new medications and treatment approaches are safe and effective.

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Kam-Hansen S, Jakubowski M, Kelley JM, et al. Altered placebo and drug labeling changes the outcome of episodic migraine attacks . Science Translational Medicine . 2014;6(218):218ra5-218ra5. doi:10.1126/scitranslmed.3006175

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By Kendra Cherry, MSEd Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."

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What can be done to control the placebo response in clinical trials? A narrative review

Affiliations.

• 1 WCG Analgesic Solutions, Wayland, MA, United States of America. Electronic address: [email protected].
• 2 University of Maryland, School of Nursing & School of Medicine, Baltimore, MD, United States of America.
• 3 University of Pittsburg School of Medicine, Pittsburg, PA, United States of America.
• 4 WCG Analgesic Solutions, Wayland, MA, United States of America; Tufts University School of Medicine, Boston, MA, United States of America.
• PMID: 34237458
• PMCID: PMC8719632
• DOI: 10.1016/j.cct.2021.106503

The desire to reduce high placebo response rates in clinical trials is a popular concept. However, few studies have rigorously examined the effectiveness of methods to control for placebo responses that are relevant to randomized controlled trials. The primary objective of this review was to evaluate the effect of experimental placebo manipulations in randomized controlled trials (RCTs). We critically reviewed studies designed to manipulate placebo responses including positive expectations regarding the effectiveness of the placebo treatment, manipulating the time spent with subjects, and training study staff and subjects to accurately report symptom severity. These efforts have generally resulted in reduced placebo response and improved discrimination between drug and placebo. Interventions that neutralize staff and subject expectations and improve the ability of subjects to accurately report symptom severity have shown the most promise. Reduction of the placebo response has the potential to accelerate the development of new therapeutics.

Keywords: Expectation measurements; Placebo effect; Placebo response; Randomized controlled trials; Training.

Copyright © 2021 Elsevier Inc. All rights reserved.

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Changes in self-reported migraine pain (0–10…

Figure 3.. Effect of an Accurate Pain…

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Towards an account of the placebo effect: a critical evaluation alongside current evidence

• Published: 07 January 2020
• Volume 35 , article number  11 , ( 2020 )

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• Phoebe Friesen   ORCID: orcid.org/0000-0002-1529-916X 1  

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This paper offers a critical analysis of several accounts of the placebo effect that have been put forward. While the placebo effect is most often thought of as a control in research and as a deceptive tool in practice, a growing body of research suggests that it ought to be thought of as a powerful phenomenon in its own right. Several accounts that aim to draw boundaries around the placebo effect are evaluated in relation to current evidence and it is argued that none of them adequately capture the variability and potency of the phenomenon. Two accounts, however, that point towards the underlying mechanisms of the placebo effect, are shown to offer promise in terms of developing a more comprehensive account of the placebo effect.

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I will use placebo effect and placebo response interchangeably in this manuscript.

Statistical regression can be accounted for by taking two baseline measures at the start of a trial.

Howick offers a modified version of Grünbaum’s account of the placebo effect, adding to the account a requirement that characteristic features are “features that are effective and not due to expectation effects” (Howick 2017 , p. 1385). While this does help solve additional concerns that have been raised in relation to the account, primarily as it relates to placebo controls rather than placebo effects, it tends to exacerbate the worries raised here. On Howick’s account, determining what constitutes a placebo effect becomes even more difficult, since requiring that characteristic factors are effective means that classification of placebogenic and nonplacebogenic effects can take place only after one has examined the efficacy of each treatment component.

It’s worth noting that many of the accounts considered here were developed at a time when the mechanisms underlying the placebo effect were less well understood, so it is unsurprising that they sought to characterize the phenomenon in these ways.

Thank you to an anonymous reviewer for encouraging me to unpack this point in more detail.

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Many thanks to Peter Godfrey-Smith, Jesse Prinz, and John Greenwood for feedback on earlier versions of this manuscript. This work was partly supported by a Doctoral Award from the Social Sciences and Humanities Research Council of Canada (Grant No. 752-2015-0433).

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Friesen, P. Towards an account of the placebo effect: a critical evaluation alongside current evidence. Biol Philos 35 , 11 (2020). https://doi.org/10.1007/s10539-019-9733-8

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The Fascinating Mechanisms and Implications of the Placebo Effect

Luana colloca.

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It is becoming clear that any treatment is significantly modulated by placebo effects in clinical settings. Placebo effects are positive outcomes that are attributable to the psychosocial context and individual treatment expectations rather than the action of the medication or intervention ( Colloca & Benedetti, 2005 ). Placebo effects also occur when placebos are given following the administration of active and effective medications (e.g., painkillers) creating drug-like effects (e.g., dose-extending placebos) ( Colloca, Enck, & DeGrazia, 2016 ). Pharmacological studies indicate that placebos mimic the action of active treatments and promote the endogenous release of opioids and nonopioids in both humans and animals. Expectations of benefit facilitate the activation of pain and nonpain control systems leading to release of endogenous substances crucially involved in placebo-induced benefits. Indeed, neurobiological studies have identified dopaminergic, opioidergic, vasopressinergic, and endocannabinoidergic pathways as promising systems contributing to the modulation of pain experience and other symptoms. This book presents recent behavioral and neurobiological advances on placebo effects and expands on well-established proposed conceptual frame-works and theories. Since placebo effects act as “boosters” of treatment expectancy and clinical outcomes, gaining deeper understanding of the top-down mechanisms of symptoms modulation and well-being has enormous implications for personalizing and optimizing pain management and other symptoms.

One area that reserves further investigation to understand the mechanisms of placebo effects is research in animals that would allow the creation of much needed molecular models to determine the underlying brain and peripheral mechanisms. Despite the opportunities and excitement of animal research, there are aspects that need to be addressed in order to advance placebo research. Gaps and controversies have been acknowledged in pain placebo research ( Keller, Akintola, & Colloca, 2018 ), but solid models and findings are provided for placebo effects in the immune system. Well-established learning paradigms have been developed in the context of the immune system in both animals and humans ( Hadamitzky, Sondermann, Benson, & Schedlowski, 2018 ), where a novel taste is used as conditioned stimulus (CS) along with the administration of immunosuppressive drugs (e.g., cyclosporine A) that act as the unconditioned stimulus (US). Subsequently, the presentation of the CS alone elicits, after a certain number of associations, the conditioned response (CR) including hormonal and body responses ( Ader & Cohen, 1975 ; Tekampe et al., 2018 ).

Importantly, when a person expects and experiences a placebo analgesic effect, cognitive and emotional circuitries are activated with experience of pain reduction and improvements in other symptoms. Molecular neuroimaging studies using positron emission tomography and the selective µ-opioid receptor tracer [ 11 C]carfentanil have greatly contributed to current understanding of the neurobiology of the placebo effect. The self-healing capacity to activate endogenous opioid and nonopioid networks associated with the administration of a placebo ( Pecina & Zubieta, 2018 ), or other surgical and pharmacological interventions, points to a sort of inner pharmacy with survival and evolutionary meanings. Partially determined by genetic factors ( Colagiuri, Schenk, Kessler, Dorsey, & Colloca, 2015 ), maintained through learning mechanisms, and sustained by the cognitive dynamic integration of expectations surrounding the therapeutic environment, patient–clinician relationship, and the act of administering an intervention, placebo effects promote symptomatic improvements.

The delineation of these mechanistic advances has been guided by theories, models, and frameworks posited to understand components of the placebo effect (e.g., motivation) as well as grab its complexity in real-world settings. For example, basic tenets of the response expectancy theory, and its distinction between response expectancies and stimulus expectancies, help uncover the individual experience of placebo-induced benefits ( Kirsch, 2018 ). On the other hand, conditioning and learning principles are relevant for placebo research because they clarify the change occurring at the behavioral and brain levels when someone is taking a pill that can contain either an active pharmacological substance or merely a drop of saline solution ( De Houwer, 2018 ).

Placebo effects and positive outcomes resulting from expectations about a treatment outcome should be considered as powerful components of modern medicine. Persuasion that involves changes in beliefs or attitudes as a result of providing critical information can be embedded in daily clinical communication. Therefore, it is clear that the practitioner’s attitudes, his confidence and competence, can at least in part favor the formation and magnitude of placebo effects ( Geers et al., 2018 ). Similarly, mindsets may represent a critical mental construct that illustrates the role of the treatment contexts in shaping placebo effects ( Zion & Crum, 2018 ). Moreover, the patient–provider therapeutic alliance contributes to placebo effects and health outcomes. Overall, the patient’s perception of the clinician, his psychosocial orientation (e.g., loneliness, poor patient–clinician relationship), and perceptions of their interpersonal relationships may broadly influence placebo effects ( Necka & Atlas, 2018 ).

Recently, compelling research is attempting to unravel how placebo effects are elicited in critical contexts with an understanding of what is minimally required to observe placebo effects from intellectual disability, to high altitudes to open-label placebos that challenge the common sense that placebo effects rely on deceptively administering placebos to patients. However, the effect of the placebo effect does not reside in the sham treatment itself; rather, it relies on expectancies that surround the patient and the intervention. Therefore, recent data suggest that patients with impaired cognitive functions may respond to placebos by virtue of implicit cognitive processes that go beyond desire, suggestions, or verbal communication (e.g., conditioning). There are minimum requirements for eliciting placebo effects, both from the view of conscious awareness and from the perspective of brain functionality ( Jensen, 2018 ).

When the brain preserves the primary ability of integrating incoming sensory information with the inner world that reflects the individual’s prior experiences, placebo effects are generated primarily to promote adaptation to old and new environments and minimize trials and errors. Placebo effects reflect the ability to merge prior experience and ideas about treatment outcomes with sensory perception reconciling mismatches between what is expected and what is experienced . Expectations and sensory inputs are both finely modulated to provide the variety of nuances used in the interpretation of facts and experiences.

With this in mind, it is not surprising that critical life functions, like ventilation, oxygenation, circulation, and perfusion, can be shaped by placebo effects also in extreme contexts such as at an altitude as high as 3500, 4500, and 5500m, where oxygen pressures are 64%, 57%, and 50%, respectively, compared to the sea level. Oxygen-related body responses can be conditioned at high altitudes ( Benedetti, Barbiani, & Camerone, 2018 ).

Placebo effects can also occur when patients know they have been given placebos. Open-label placebos can be interpleading in paradigms with therapeutic treatments so that learning and nondeceptive approaches are harnessed to minimize drug intake while reducing side effects and costs. Although there are distinct differences between open-label and dose-extending placebos, use of such placebos can be preauthorized (e.g., patients agree to receive, at some point, placebos along with medication) in accordance with professional norms governing disclosure and informed consent, and be used in combination with a standard use of treatment ( Colloca & Howick, 2018 ).

Without invoking the use of any placebos, expectations can be shaped to make a treatment and/or an outcome most effective via psychotherapy. Indeed, there is a compelling notion that the placebo effect and psychotherapy represent two psychological interventions that share much more than their first letter ( Gaab, Locher, & Blease, 2018 ). Through psychotherapy, communication, and framing styles, expectations can be positively manipulated as indicated by a recent randomized-controlled trial (RCT). A presurgery expectation optimization program, applied to patients scheduled for coronary artery bypass grafting, resulted in lower disability scores at 6-month post-surgery follow-ups ( Rief et al., 2017 ). Expectations can be changed by a series of procedures with the scope to optimize outcome in medical settings ( Doering, Glombiew, & Rief, 2018 ).

However, expectancy, patient–clinician relationships, and prior therapeutic histories can be negative, thus compromising clinical outcomes. The negative counterpart of the placebo effect is named “nocebo” effect ( Colloca, 2017a , 2017b ; Klinger, Blasini, Schmitz, & Colloca, 2017 ), and despite its relevance for modulation of mechanisms and clinical implications, the nocebo phenomenon has received less attention over the past decades than the placebo effect. However, laboratory and translational research is unraveling some of the behavioral and biological mechanisms as well as the clinical implications. Nocebo effects have been investigated in the field of pain (e.g., experimental acute and visceral pain) ( Elsenbruch & Labrenz, 2018 ; Kleine-Borgmann & Bingel, 2018 ), nausea ( Quinn & Colagiuri, 2018 ), and other symptoms. Particular emphasis has been given to visceral pain, a model used for behavioral and neuroimaging studies that has helped foster the understanding of nocebo as compared to placebo mechanisms. The recent findings facilitate the transition of experimental research from bench to bedside and ways in which the environment can be manipulated to prevent, reduce, or eradicate nocebo effects ( Elsenbruch & Labrenz, 2018 ). Preexposure to placebo stimulation (latent inhibition) prevents nocebo effects in experimental conditioned nausea ( Quinn & Colagiuri, 2018 ).

Learning strategies, including overshadowing, latent inhibition, extinction, and contingency degradation, represent future research avenues that, if transitioned from bench to bedside, might promote strategies to reduce unintended nocebo effects to be used by clinicians and researchers while designing trials to test new interventions ( Quinn & Colagiuri, 2018 ). Indeed, randomized controlled trials have shown an increased trend to fail, which may be due to both nocebo and especially placebo responses. The neurobiology of placebo effects highlights that patients’ expectations interfere with the response to medications and therefore, new clinical trial approaches should be used to improve drug development ( Vase & Carlino, 2018 ).

This series of 18 articles found their inspiration during the first meeting in 2017 of the Society for Interdisciplinary Placebo Studies (SIPS, https://www.placebosociety.org/ ) that is a newly created international association of scholars who share the goal of understanding the placebo effect in medical treatment, psychotherapy, and complementary and integrative medicine by promoting communication and cooperation between research centers and scholars. By using multidisciplinary approaches including neuroscience, psychology, anthropology, and philosophy, it may be possible to expand knowledge on the neurobiological mechanisms and brain functions as well as fully appreciate the implications of this research to develop ethically acceptable ways to harness placebo effects with the scope to optimize clinical trial designs, treatment outcomes, and therapeutic strategies.

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