In the decades after Dr. Beecher’s trials, researchers investigated what caused this effect. Some proposed that it was predominantly psychological — an instance of mind over matter — while others found possible biological origins. Scientists discovered that naloxone, a drug developed for patients who overdose on opiates, partly prevented placebo effects, suggesting that the pain relief experienced after taking a placebo might be produced, in part, by activating opioid receptors in the central nervous system.
By the time Dr. Maher was completing his training in physical therapy in the 1980s, Dr. Beecher’s trials were already ingrained in medical folklore, even leaking into popular culture.
Dr. Maher recalls a M*A*S*H episode in which the medics fill capsules with sugar scraped from doughnuts to give to wounded soldiers after the morphine supply had run out. “Like everyone, I just accepted that it could actually work,” he said.
His view changed after 2001, when two Danish researchers, Asbjorn Hrobjartsson and Peter C. Gotzsche, published a paper in the New England Journal of Medicine arguing that medical studies had exaggerated placebo effects. They identified what they said was a flaw in the studies’ designs: Many failed to compare patients who had received placebos against a control group of patients who had not.
In such studies, the Danish researchers argued, it was impossible to know whether it was the placebo that was working or something else entirely, like natural healing. When they reviewed studies that did compare placebo groups to no-treatment groups, they found that the placebo effect more or less disappeared.
The paper kicked off a debate about study design in placebo research. Dr. Maher, who was by then working in clinical research at the University of Sydney, was initially convinced that the Danish researchers had made a mistake. But when he and one of his students replicated their study, they essentially got the same result.