Studying the placebo effect

Often, when studying a new drug, researchers compare the drug to a “sham drug” or placebo. They do this because, no matter what the problem, a certain percentage of study subjects, as many as 50 percent, may improve with just the placebo. To test how much better the study drug is, it must be measured against the placebo.

Suppositions abound for the efficacy of placebos. Until recently, doctors believed that the placebo effect was psychological. The old “it’s-all-in-your-head” excuse. Of course, most of what we are – our feelings, our emotions, our interactions with the world at large – is all in the brain, which resides in, of course, our head. If the patient, and even his doctor, believes the placebo is the real thing, that belief can have a powerful effect. Thus, the justification for double-blind studies, where neither the patient nor the doctor know which drug is the real thing.

Well, as we are beginning to find out, that powerful effect comes from chemical messengers in our brain. Now we have the ability to image the brain as we watch its reaction to various events.

Researchers at the University of Michigan wanted to study the placebo effect, so they recruited 14 young healthy men to participate in their research. The men, between the ages of 20 and 30, agreed to let researchers inject their jaw muscles with a concentrated salt-water solution to cause pain. (What some people will do for science!) The injections took place when the men were having their brains imaged with a PET scanner. During the scan, half the men were told they would receive medication that might relieve their pain. The other seven men did not receive the placebo.

The PET scans looked specifically at the areas of the brain known to be the centers of the brains natural painkillers – endorphins or “endogenous opioids.” Endorphins bind to specific receptors on brain cells and, by so doing, block the transmission of pain signals from one cell to the next. These receptors are also the site of actions for drugs such as morphine, methadone and anesthetic agents.

Every 15 seconds, the study participants were asked to rate their pain on a scale of 0 to 100. Every four minutes, the men who got the placebo received a small intravenous dose of a hydrating solution.

But here was the clever part of the experiment: At the same time the researchers were giving the placebo, they were also slowly increasing the amount of salt solution in order to keep the subjects’ pain ratings steady. The subjects were not aware that the pain-causing solution was being slowly increased.

The endorphin system tries to squelch pain whenever it occurs. So, if the pain rating stayed the same in the face of increasing pain-causing solution, that implied a reduction in pain sensitivity. And that implied an increase in endorphin production.

The subjects who got the placebo showed an increase in endorphin activity on their PET scans when they were told that the “medicine” was coming. The largest increases were in the areas of the brain known to be involved in responding to and processing pain.

Even more interesting was that different parts of the brain were activated depending on what response the subjects were describing.

Different areas lit up with the expectation of pain, the intensity of pain, how unpleasant the pain was, and the subjects’ emotional response to the pain.

And so the researchers have concluded that the placebo response is not purely psychological but based on real physical changes that can be imaged and quantified. Not only does this study confirm the role of those wonderful endorphins in the placebo response, but it confirms that we each possess the power to control, at least to some degree, our own responses to pain.

This opens the door to more research into cognitive, or nondrug, methods to control pain.

So where can I buy stock in that placebo stuff?