Placebo-induced improvements: how therapeutic rituals affect the patient's brain

The placebo effect has evolved from being thought of as a nuisance in clinical research to a biological phenomenon worthy of scientific investigation. The study of the placebo effect and of its evil twin, the nocebo effect, is basically the study of the therapeutic ritual around the patient, and it plays a crucial role in the therapeutic outcome. In recent years, different types of placebo responses have been analyzed with sophisticated biological tools that have uncovered specific mechanisms at the neuroanatomical, neurophysiological, biochemical, and cellular levels. Most of our knowledge about the neurobiological mechanisms of the placebo response comes from pain and Parkinson's disease, whereby the neuronal networks involved in placebo responsiveness have been identified. In the first case, opioid, cannabinoid, and cholecystokinin circuits have been found to be involved. In the second case, dopaminergic activation in the striatum and neuronal changes in basal ganglia have been described. This recent research has revealed that these placebo-induced biochemical and cellular changes in a patient's brain are very similar to those induced by drugs. This new way of thinking may have profound implications in clinical trials and medical practice both for pharmacological interventions and for nonpharmacological treatments such as acupuncture.