A sham surgery that leaves chronic pain gone, a sugar pill that eases nausea, a saline injection that outperforms a capsule: the placebo effect is one of medicine’s most enduring puzzles. This episode starts with the Latin meaning of the word, I shall be pleasing, and untangles the difference between a placebo response and a true placebo effect, explaining why regression to the mean and patients’ desire to please their doctors make the phenomenon so hard to measure.

From there it digs into the biology: fMRI studies showing the prefrontal cortex, orbitofrontal cortex, and amygdala at work, the release of endogenous opioids known since 1978, and top-down control that changes how the spinal cord handles pain signals. It covers classical conditioning experiments in which a sweet drink alone suppressed the immune system, the strange rules of placebo theater, the anthropology of ritual healing described by Claude Levi-Strauss, open-label placebos that work even when patients know they are inert, and the nocebo effect, including women who reported withdrawal after nearly six years on a placebo.

• Why a 2010 Cochrane review found placebos do not cure organic disease but do change pain and nausea
• Two pills beat one, capsules beat tablets, and red versus blue pills matter
• The practitioner effect and why bedside manner is a biological catalyst
• The Irving Kirsch antidepressant controversy and the reanalysis that revised his 82 percent figure
• The ethics of prescribing placebos, from physician surveys to the UK ruling on homeopathy