The Placebo Paradox

The word placebo is Latin for I shall please, and for most of medical history it carried a faint air of deception. A placebo was what a doctor gave a patient who demanded treatment for an illness that had none: a sugar pill, a colored tonic, a reassuring injection of salt water. That such remedies sometimes appeared to work was regarded less as a scientific puzzle than as evidence of the patient's suggestibility. Over the past few decades, however, the placebo has turned from an embarrassment into one of the more intriguing subjects in medicine.

Part of the reason is that placebos are built into the foundations of modern research. In a randomized controlled trial, a new drug is compared not with nothing but with an identical-looking dummy, precisely because patients given a dummy so often improve. In 1955 the American anesthesiologist Henry Beecher published an influential paper suggesting that around a third of patients responded to placebos. Later researchers have argued that his figures were inflated, since many patients would have recovered anyway, illnesses naturally fluctuate and people tend to seek help when their symptoms are at their worst. Even allowing for all that, a genuine effect seems to remain.

What that effect consists of is now better understood, at least for pain. In the late 1970s, researchers found that the pain relief some patients obtained from a placebo could be reduced by naloxone, a drug that blocks the action of opioids. This suggested that expectation was doing something physical: prompting the brain to release its own painkilling chemicals. Brain-imaging studies have since supported the idea that, under the right conditions, belief can alter the way pain signals are processed. Conditioning appears to play a part as well. A patient who has repeatedly felt better after taking a certain pill may come to respond to its appearance alone.

The effect has an unwelcome twin. In the nocebo effect, negative expectations produce real symptoms. Participants in clinical trials who receive a dummy pill regularly report side effects, often the very ones they were warned about in the consent form. A British study published in 2021, in which patients who had abandoned cholesterol-lowering statins took real tablets, dummy tablets and no tablets in different months, found that the great majority of the symptoms they attributed to the drug were also present when they were taking the dummy.

The most paradoxical finding concerns what are known as open-label placebos. In a small but widely discussed study published in 2010, researchers at Harvard gave patients with irritable bowel syndrome pills that they were told, quite honestly, contained no active ingredient. The patients nevertheless reported significantly greater improvement than a comparison group who received no pills at all. Similar results have since been reported for chronic back pain and other conditions, although the studies have generally been small and relied on what patients said about their own symptoms.

That last point is crucial, because placebos have clear limits. They do not shrink tumors, clear infections or lower cholesterol. In one revealing experiment, asthma patients said they felt almost as much better after a dummy inhaler as after a real one, yet measurements of their lungs showed that only the genuine medication had improved their breathing. Placebos, it seems, act chiefly on how symptoms are experienced, not on the disease underneath.

None of this means that doctors should start prescribing sugar pills. It does suggest that the ritual surrounding treatment, including the time a doctor spends listening, the confidence with which a remedy is offered and the words used to describe its risks, may influence how patients feel to a greater degree than we once assumed. The mind, in other words, cannot cure everything. But it is rather more involved in getting better than modern medicine has often been willing to admit.