09/10/2012 11:36 am ET Updated Nov 10, 2012

Can a Spoonful of Sugar Really Help the Medicine Go Down?

If Granny sits at your bedside and assures you that her chicken soup cures even the worst colds and flu, or if your neighbor swears that a special liniment sold by a vendor only he knows works magic with sore muscles, bad knees and achy backs, should it be surprising to clinicians and researchers that, by golly, sincerely touted remedies and nostrums do sometimes appear to work?

Or do they?

Even the most careful physician or scientist must be cautious about a too human characteristic: hungering to believe in something so much that we think it becomes so. We've all encountered in some fashion the power of pure faith. But in medicine, especially when it comes to therapies and evaluating what works and what doesn't, it's crucial even in the 21st century to be wary of what once was dubbed the placebo effect, or as it more properly should be labeled, the placebo response.

The investigative record in science is filled with fascinating incidents in which even the savviest of subjects provided startling, often positive responses to treatments known to be ineffective or medications that in reality were inert substances — sugar pills or the like. The mind's power to deceive itself, with a little sweet talk or diversion, can be formidable.

Take what happened to some of the 612 men with enlarged prostate glands who were given either the drug Proscar or a placebo. An enlarged prostate can impede the flow, making urination difficult and uncomfortable. In the study, the prostates of men taking the real drug shrunk an average of 21 percent, so it's unsurprising they reported an improvement in urine flow. But the prostates of men taking placebo pills not only didn't shrink, they actually grew by more than 8 percent. Still, those on placebo reported improved urine flow, and objective measures showed it actually had improved. The lead researcher reported that some men didn't want to stop taking the placebo, so convinced were they that it was helping them.

The placebo response probably has been part of the healing equation for as long as people have been around. After all, it's only in the past 100 or so years that we've been helped by modern medicine: anesthesia, infection control, hygienic surgery, antibiotics and our vast arsenal of pharmaceuticals. Before those advances, people suffered and died young. But we can imagine that some patients were, indeed, helped by holy oil, the flesh of vipers, the horns of deer or the eyes of newts, along with the comforting touch and words of physicians and other caregivers.

Historical Perspective

Thomas Jefferson said that one of the best physicians he knew claimed to use more concoctions of bread pills, colored water and hickory ashes than all other medicines combined. Jefferson called the practice a "pious fraud."

But as physicians began to take seriously the therapeutic value of such well-meaning deceptions, among the first to study it was researcher Harry Beecher. In 1955, he published a paper with impact titled, "The Powerful Placebo." In it, he reviewed15 placebo-controlled studies and concluded that the magnitude of the placebo effect was 35 percent. He was correct in taking the placebo effect seriously. But he was wrong in assigning a universal number. Among other things, he failed to consider the effect of no treatment. The natural course of disease could have accounted for some improvement. But his paper changed minds and probably accounts still for the misperception that the placebo effect can account for a fixed fraction, or about one-third, of patient response to treatment.

Those who doubt alternative medicine — homeopathy, acupuncture or meditation — might suggest that benefits from such practices are nothing more than the placebo effect. Others look at the benefits of a sympathetic ear and suggest that a physician's caring interaction is a placebo effect equivalent.

Abundant Examples

There is ample evidence that placebos make an impact on patients' health.

We can look to a classic study involving medical students, who were told they were taking part in a study of two new drugs, one a tranquillizer and the other a stimulant. Each student was given one or two pills, either red or blue. All the pills were fakes, yet when students were asked to report these pills' effect, those taking the reds swore they acted as a stimulant. Those popping the inert blues were sure they were depressants. And when the students took two pills instead of just one, the effect — stimulation for red, depression for blue — increased.

In another study, women reported more headache relief when they believed they were taking an aspirin with a widely recognized brand name rather than the same brand name aspirin as a generic preparation. When they received a placebo in the brand name aspirin package, they got more headache relief than when given the same placebo given as generic "aspirin."

Even invasive procedures have been put to the placebo test in something called sham surgery. One of the earliest examples was a procedure called mammary artery ligation surgery, once thought to relieve symptoms of angina. But when patients were put through the rigors of the surgical suite without actually having the procedure, they improved as much as those who got the real surgery. That research finding effectively put an end to that procedure as an angina treatment.

It's All in Your Brain

Rather than a dismissive attitude that the placebo effect proves it's all in your head, science is showing that placebo treatment can result in actual neurological changes. One study involving 17 men hospitalized with major depression were divided into two groups, one group treated with Prozac® and the other with a placebo. After six weeks, researchers took a look at their brains using PET scan technology. They found many similar changes to the brains of all the men in areas associated with depression, whether the men were taking the real antidepressant or a placebo. Those taking Prozac, however, had additional brain changes as well, not seen in the placebo group, which could help prevent future relapses.

Another study using a different form of brain functional assessment called quantitative electroencephalography also found brain changes in depressed patients from placebo treatment. But in both studies, the relief from depression didn't last for those given a placebo. The improvement from the sham pills was short term and those taking them relapsed shortly after the study ended.

Some studies have shown that injecting a salt water solution into patients that believe it is an analgesic drug can relieve pain, and that this effect can be blocked by giving a drug called naloxone which blocks the effects of strong opiates such as morphine. Naloxone's effect on blocking the pain relief provided by the salt water placebo indicates that the subjects released their own endorphins, which are our brains natural opiates.

Such studies show that the placebo effect is not the result of taking "nothing." Rather, the attention of health care providers, the interpersonal relationships involved in being a study subject, the process of taking a pill and believing in its benefits, all factor into creating at least a short-term physiological healing response. Encouraging the belief that patients' symptoms are taken seriously, and that trusted people are working to help them can be beneficial, though not the entire solution.

Our Bodies, Our Minds

We have learned enough about the connection between our minds and our bodies to know that seeing an illness, or an improvement in symptoms, as "all in your mind" is not an insult. It is the way we work, our physical bodies linked to our thoughts and perceptions. We all have an ability to exert some cognitive control over our bodies. And our subconscious minds, along with words and encouragement from our health care providers, can work along with so-called real medicine to help our bodies feel better.

I'll write more soon about clinical trials and the rigorous steps researchers take to ensure that participants in this important part of modern medicine play a careful, safe and scientifically correct role in advancing our knowledge about diseases and their treatment. It may be tempting to race ahead with all manner of therapies because we want to believe in their efficacy — and many may indeed be showing some positive outcomes. But the placebo effect offers us a strong reminder that part of sound science is the meticulous process of controlling for as many variables as possible to isolate the true effect of a drug or other treatment. And in clinical medicine, the placebo effect should provide a different reminder to harried 21st century caregivers — time and attention, as in humane, thoughtful dialogue and compassion, always will be part of the healing process in dealing with the ill. It's a memorable lesson that Grandma and Mary Poppins taught us all long ago.