placebo

A placebo is an inert substance or sham procedure that has no specific therapeutic effect but can influence a patient’s symptoms through psychosocial and neurobiological processes. The word comes from Latin placere, meaning to please. In clinical research, a placebo serves as a control condition in randomized, double-blind trials to distinguish the effects of an active treatment from those of expectations, natural history, and other non-specific factors. Placebos can take the form of a sugar pill, saline injection, or a sham procedure that mimics real intervention without delivering its therapeutic component.

Historically, the term appeared in English in the 18th century, and the use of placebos as controls became central to modern clinical trials in the 20th century. Placebos are often contrasted with active therapies, and trial designs frequently require that neither participants nor researchers know who receives the active treatment to prevent bias.

The placebo effect arises from expectancy, conditioning, and the context of care, including the patient–clinician relationship. Neurobiological mechanisms have been identified in some conditions, such as analgesia and mood disorders, involving endogenous opioids, dopamine, and other neurotransmitter systems, as well as modulation of pain-processing brain regions.

Placebos have demonstrated meaningful short-term improvements in subjective symptoms in various conditions, but they do not provide evidence of disease modification. Ethical considerations center on the use of deception; open-label placebos, where participants know they receive a placebo, have shown some effect in certain settings, highlighting ongoing debates about consent and transparency in practice. Placebos remain a fundamental tool in assessing treatment efficacy and understanding mind–body interactions.