John M. Talmadge, M.D.

A Blog Covering Many Topics

Genetics, Weird Facts, & Placebos

There are times when the practice of medicine is the most fascinating possible kind of work. For example, consider the placebo effect.

A placebo is anything that seems to be a "real" medical treatment -- but isn't. It could be a pill, a shot, or some other type of "fake" treatment. What all placebos have in common is that they do not contain an active substance meant to affect health. Younger physicians won't remember this, but years ago it was considered okay for doctors to prescribe placebos. Surgeons fairly often would substitute saline (salt water) injections when they worried that patients were asking for too many narcotic shots after an operation. There was a preparation called Gevrabon that was essentially sherry wine with some vitamins added, and it could be given by prescription "for relaxation at bedtime." Over the years, for obvious reasons, experts in medical ethics began to question whether these practices—essentially deceiving patients, but with good intentions—were proper and permissible.

In addiction medicine, I've seen college students come into the emergency room looking drunk, only to discover (with lab verification) that the "drug" they had tried was simply a vitamin pill. Similar findings have emerged at The University of Texas Austin, where one of the research labs has a full-fledged bar (i.e. a saloon) set up to simulate the settings where college students drink. Click here to see the Sahara Bar in the Department of Psychology. Study subjects sometimes get tipsy even when their margarita or manhattan contains no alcohol at all.

In 1996, scientists assembled a group of students and told them that they were going to take part in a study of a new painkiller, called "trivaricaine". Trivaricaine was a brown lotion to be painted on the skin, and smelled like a medicine. But the students were not told that, in fact, trivaricaine contained only water, iodine, and thyme oil – none of which are painkilling medicines. It was a fake – or placebo – painkiller. Read an abstract of the study: Mechanisms of Placebo Pain Reduction. With each student, the trivaricaine was painted on one index finger, and the other left untreated. In turn, each index finger was squeezed in a vice. The students reported significantly less pain in the treated finger, even though trivaricaine was a fake.

In this example, expectation and belief produced real results. The students expected the "medicine" to kill pain: and, sure enough, they experienced less pain. This is the placebo effect.

Placebo medicine has even been shown to cause stomach ulcers to heal faster than they otherwise would. These amazing results show that the placebo effect is real, and powerful. They mean that fake or placebo treatments can cause real improvements in health conditions: improvements we can see with our own eyes. Experiencing the placebo effect is not the same as being "tricked", or being foolish. The effect can happen to everyone, however intelligent, and whether they know about the placebo effect or not.

An article in Harvard Magazine describes Harvard Professor Dr.Ted Kaptchuk’s first randomized clinical drug trial, where nearly a third of his 270 subjects complained of awful side effects. All the patients had joined the study hoping to alleviate severe arm pain: carpal tunnel, tendinitis, chronic pain in the elbow, shoulder, wrist. In one part of the study, half the subjects received pain-reducing pills; the others were offered acupuncture treatments. And in both cases, people began to call in, saying they couldn’t get out of bed. The pills were making them sluggish, the needles caused swelling and redness; some patients’ pain ballooned to nightmarish levels. “The side effects were simply amazing,” Kaptchuk explains; curiously, they were exactly what patients had been warned their treatment might produce. But even more astounding, most of the other patients reported real relief, and those who received acupuncture felt even better than those on the anti-pain pill. These were exceptional findings: no one had ever proven that acupuncture worked better than painkillers. But Kaptchuk’s study didn’t prove it, either. The pills his team had given patients were actually made of cornstarch; the “acupuncture” needles were retractable shams that never pierced the skin. The study wasn’t aimed at comparing two treatments. It was designed to compare two fakes.

Dr. Kaptchuk and his colleagues have found that placebo treatments—interventions with no active drug ingredients—can stimulate real physiological responses, from changes in heart rate and blood pressure to chemical activity in the brain, in cases involving pain, depression, anxiety, fatigue, and even some symptoms of Parkinson’s. His work was also featured in a New Yorker article, "The Power of Nothing," that can be found here.

Here are four fascinating (and weird) facts about placebos and the placebo effect:

1. It doesn't have to be a secret. Some believe that a placebo can only work if the recipient is unaware they are taking one. But there's evidence that people with irritable bowel syndrome who knowingly receive a placebo do better than those who are left untreated.

2. It works better if it's expensive. The pain-killing power of a placebo pill is greater among people who are told they are taking a full-price version, compared to those told that the pill is on sale for a discounted price.

3. It's not just us, animals can get it too. A 2012 study found that between 30 and 40 per cent of rats experienced pain relief when their morphine injections were swapped for inactive saline solution.

4. It has an evil twin. The nocebo effect makes people undergoing treatment more likely to suffer from side-effects if they are warned about them by their doctor.

For the full New Scientist journal article on the subject, click here.

Slowly, over the past decade, researchers have begun to tease out the strands of the placebo response. The findings, while difficult to translate into medicine, have been compelling. In most cases, the larger the pill, the stronger the placebo effect. Two pills are better than one, and brand-name pills trump generics. Capsules are generally more effective than tablets, and injections produce a more pronounced effect than either. There is even evidence to suggest that the color of medicine influences the way one responds to it: colored pills are more likely to relieve pain than white pills; blue pills help people sleep better than red pills; and green capsules are the best bet when it comes to anxiety medication.