3 Clinical psychopharmacology3.1 General pharmacology
3.1.2 The placebo effect
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Written by Resident Doctor Committee · Published
Definitions
Term | Meaning |
|---|---|
Placebo | An intervention that matches the treatment context without its active component |
Placebo response | All change seen after a placebo |
Placebo effect | Change caused by expectation, context or learning |
Nocebo effect | Unwanted effects caused by the recipient's negative expectation, not by any property of the substance |
The nocebo effect runs in parallel to the placebo response and is not one of its mechanisms.
Types of placebo
Type | Nature | Use |
|---|---|---|
Inert | A dummy preparation with no pharmacological activity | Matches the drug's appearance and schedule |
Active | Has pharmacological effects of its own, usually mimicking the test drug's side effects, but none on the condition (atropine, for example) | Protects blinding |
An inert placebo can be unmasked when patients recognise the side effects of the real drug.
Psychological mechanisms
Expectation shapes the response: credible explanations, clinician behaviour and presentation cues all strengthen it.
Branding increases the placebo effect: an identical inert tablet relieves symptoms more when it carries a familiar brand.
Conditioning makes placebo and nocebo learned responses, so earlier adverse experience with a drug can condition later nocebo responses.
Biological mediation
Placebo analgesia is partly mediated by endogenous opioids, shown by its reversal with naloxone.
Dopamine, endocannabinoids and oxytocin also mediate placebo effects; in Parkinson's disease a placebo releases striatal dopamine.
Nocebo hyperalgesia partly involves cholecystokinin signalling.
Course and who responds
Placebo improvement is typically transient, fading as expectation wanes.
Placebo responders do not share a fixed personality type.
Why a placebo group improves
The placebo response is larger in mild illness than in severe illness. The usual explanations are:
Regression to the mean, which follows unusually high entry scores.
Spontaneous remission, as symptoms improve naturally.
Expectation in participants and assessors, together with supportive trial contact and monitoring.