B06 - lecture 12 - Placebo and nocebo effects

What is the placebo effect?

is a reduction in symptoms caused by the person’s expectation of improvement during a therapeutic intervention. It involves real neurobiological and psychological processes.

What is the nocebo effect?

occurs when negative expectations lead to adverse symptoms, even in the absence of an active harmful agent.

What is an early historical example of placebo usage?

In 1799, John Haygarth demonstrated the placebo effect with "Perkins Tractors" by using fake replicas that provided perceived therapeutic benefits purely through suggestion.

What is an example of psychological mechanisms behind the placebo effect?

beliefs and expectations

What is an example of neurological mechanisms behind the placebo effect?

activation of opioid and dopamine pathways

What is an example of physiological mechanisms behind the placebo effect?

symptom relief, relaxation

Which brain areas are activated in placebo responders?

The orbitofrontal cortex, anterior cingulate cortex, and periaqueductal gray substance.

How do classical conditioning contribute to the placebo effect?

Classical conditioning pairs a neutral stimulus with a therapeutic effect (e.g., placebo + analgesic),

How do operant conditioning contribute to the placebo effect?

operant conditioning reinforces expectations through observed outcomes.

What role does expectation play in the placebo effect?

is mediated by the prefrontal cortex and significantly influences pain relief and symptom perception. Positive expectations can enhance treatment outcomes.

How does the placebo effect work in Parkinson’s disease?

It triggers the release of endogenous dopamine in the striatum, improving motor function through "teaching neurons to respond to placebos."

What percentage of side effects in COVID-19 vaccine trials were attributed to the nocebo effect?

76%, according to a meta-analysis of 12 studies involving 45,380 participants.

What is the impact of framing on placebo and nocebo effects?

Positive framing (e.g., "1 in 3 will benefit") enhances outcomes, while negative framing (e.g., "2 in 3 will not benefit") can lead to nocebo effects.

How can clinicians reduce the nocebo effect?

By using positive verbal suggestions, fostering trust, managing patient expectations, and avoiding negative framing of potential side effects.

What is the role of endogenous opioids in placebo analgesia?

Placebo treatments can stimulate the release of endogenous opioids (e.g., endorphins) in the brain, activating pain-relieving pathways.

How are placebo responses mediated in non-opioid systems?

Non-opioid-mediated placebo effects involve other pathways, like conditioned responses to NSAIDs, demonstrating flexibility in the biological mechanisms.

What is a notable case study of a nocebo effect involving placebo pills?

A 26-year-old believed he overdosed on pills from a clinical trial, experienced severe symptoms (low blood pressure, lethargy), and only recovered once informed the pills were inert.

How does pre-exposure influence nocebo effects?

Patients pre-exposed to discussions of side effects (40-90%) are more likely to report those side effects, even when receiving a placebo.

What are key strategies for leveraging the placebo effect in clinical practice?

Strengthening the therapeutic relationship, framing treatment positively, reducing anxiety, and creating positive expectations.

What are the limits of the placebo effect?

While it affects symptom perception and has biological impacts across systems, the placebo does not directly cure underlying conditions.

What should clinicians assess about patient expectations?

Their beliefs, previous failed treatments, prejudices, and expectations of current interventions to better tailor communication and therapy.

Can placebo effects occur without deception?

Yes, open-label placebos (where patients are informed they’re receiving a placebo) can still lead to significant improvements.