What causes the placebo effect?

From the Guidelines

The placebo effect is primarily caused by a combination of psychological and neurobiological mechanisms, including social learning, classical conditioning, and explicit instruction, which create real physiological changes in the body, as evidenced by the most recent and highest quality study 1.

Key Mechanisms

• Social learning: individuals modify their beliefs and behaviors after observing the behavior of others, which can shape their expectations and experiences, particularly within health contexts 1.
• Classical conditioning: a neutral conditioned cue is repeatedly paired with an active unconditioned stimulus, leading to the conditioned cue eliciting adverse outcomes when presented alone 1.
• Explicit instruction: physicians inform patients that they may experience enhanced pain, increased symptom severity, or adverse side effects, which can induce nocebo effects 1.

Factors Influencing the Placebo Effect

• Individual differences in empathy: more empathic individuals are more strongly influenced by social modeling, with a small but significant positive association between empathy and nocebo outcomes 1.
• Medium and length of social modeling manipulations: longer modeling manipulations are associated with stronger nocebo outcomes, although this effect is small and should be interpreted with caution 1.
• Gender of the model and observer: studies with higher proportions of female participants and studies in which only female social models could be observed demonstrated weaker nocebo effects, although the results are complicated and require further investigation 1.

Clinical Implications

• Healthcare providers should be aware of the potential for social learning and nocebo effects in their patients, and take steps to minimize these effects, such as providing clear and accurate information about treatments and their potential side effects.
• The therapeutic relationship between healthcare providers and patients is crucial in enhancing the placebo response, with caring interactions, empathetic communication, and the ritual of treatment delivery contributing significantly to the placebo effect.

From the Research

Causes of the Placebo Effect

The placebo effect is a complex phenomenon that involves multiple mechanisms and factors. Some of the key causes of the placebo effect include:

• Expectation: The belief that a treatment will be effective can have a significant impact on the actual outcome, as shown in studies such as 2 and 3.
• Conditioning: Classical conditioning, where the brain associates a particular stimulus with a response, can also contribute to the placebo effect, as discussed in 4 and 3.
• Neurobiology: The brain's 'inner pharmacy' and the release of neurotransmitters such as dopamine and endorphins can play a crucial role in the placebo effect, as explained in 5, 6, and 3.
• Emotion and motivation: The emotional state and motivation of an individual can influence their response to a placebo, as mentioned in 5 and 4.
• Social learning: The influence of others, such as healthcare providers, can also shape an individual's expectations and response to a placebo, as discussed in 5.

Mechanisms of the Placebo Effect

The mechanisms underlying the placebo effect are not fully understood, but research has identified several key factors, including:

• The release of neurotransmitters such as dopamine and endorphins, which can mimic the effects of active drugs, as shown in 6 and 3.
• The activation of brain areas involved in pain, emotion, and reward processing, as demonstrated in 6 and 3.
• The role of expectation and conditioning in shaping the brain's response to a placebo, as discussed in 2, 4, and 3.

Implications of the Placebo Effect

The placebo effect has significant implications for clinical practice, including:

• The potential to enhance the effectiveness of treatments by promoting positive expectations, as suggested in 2.
• The need to consider the role of placebo mechanisms in clinical trial design, as discussed in 5 and 4.
• The potential to harness the benefits of the placebo effect in clinical practice, as mentioned in 5 and 6.