Placebos trigger an opioid hit in the brain

It seems that placebos have a real physical, not imagined, effect – activating the production of chemicals in the brain that relieve pain, a new study suggests.

Placebos are treatments that use substances which have no active ingredient. But if people are told that what they are being given contains an active painkiller, for example, they often feel less pain – an effect that has normally been considered psychological.

Recent studies, though, suggest otherwise. For example, when a placebo was secretly mixed with a drug that blocks endorphins – the body’s natural painkillers – there was no placebo effect, showing that endorphins are involved in the placebo painkiller process (New Scientist print edition, 26 May 2001, p 34).

Now Jon-Kar Zubieta’s team at the University of Michigan at Ann Arbor, US, has confirmed that placebos relieve pain by boosting the release of endorphins.
Pain maintainer

Fourteen healthy males in their twenties volunteered to try what they were told was “a medication that may or may not relieve pain”. To induce pain, the researchers gave the young men infusions into the jaw that made them ache.

During the experiment, the volunteers had to rate the intensity of pain every 15 seconds on a scale of 1 to 100; most judged it to be about 30. Unbeknown to them, the measure was used to keep pain constant by increasing or decreasing the infusion of the pain-inducer.

This pain management was necessary because the body’s own opioids – the endorphins – tend to alleviate pain slightly over time, and the researchers wanted to separate this effect from that caused by the placebo.
PET detective

All the volunteers, who were given a placebo of salt solution, reported feeling less pain. But the researchers did not simply take their word for it: instead, they scanned the volunteers’ brains using positron emission tomography (PET). They had injected the volunteers with a radioactive tracer that binds to the same mu-opioid receptors as endorphins do, which allowed them to figure out the level of endorphins produced in each volunteer’s brain.

The young men, who acted as their own controls, were scanned three times: before the experiment began, when they were in pain but had not yet been given the placebo, and after they had been given the placebo. Half the volunteers experienced the pain-only condition first, while the other half got the benefit of the placebo first.

The scans revealed that after the volunteers took the placebo, their brains released more pain-relieving endorphins than normal. Zubieta thinks the placebo effect is piggybacking on the body’s innate painkilling system. “[The system] is there to ensure the survival of the organism,” he says. “The placebo effect is acting through these mechanisms.” But exactly how it does this remains a mystery.

Journal reference: The Journal of Neuroscience (vol 25, p 7754)