The first real, physical proof of the placebo effect came in 1978. Running a study on patients who had recently had their wisdom teeth removed, researchers gave some of them a placebo. (The other group got naloxone, a drug that blocks the brain’s natural painkillers.) When some patients from the placebo group were later given naloxone as well, the drug counteracted the pain relief they initially got from the dummy drug.
But the effect wasn’t universal—the naloxone only made a difference among people who had reported pain relief in the first place, a group the authors called “placebo responders.” Among the non-responders, the naloxone didn’t cause any additional pain, leading the researchers to conclude that placebos worked in responders by activating the brain’s natural painkillers.
In partially answering one question—now, finally, scientists had some idea about the underlying mechanism of the placebo effect—the study, published in The Lancet, also raised a new one: Why does the placebo effect work in some people and not others? Or, put another way, what did the responders have that the non-responders didn’t?
The answer is complicated by the fact that “the placebo effect” is more accurately a tangle of interrelated effects, all of which are still closer to theory than to scientific fact. Some studies have shown that personality traits, like thrill-seeking and altruism, may have something to do with it. Other scientists say that the ritual surrounding the medicine—the explanation, reassurance, and simple human connection that a doctor can provide—may be as powerful as actually taking the sugar pill, or the saline solution. (In some cases, the placebo has done its job even when the patients knew full well that it wasn’t the real thing.)