A History of Placebos and Their Regulations

From a Lecture Series Presented by Professor Ronald Siegel, Psy.D.

For over 50 years, doctors have used placebos to cause real effects through fake cures. Placebos include pills, acupuncture, and surgeries just to name a few. How have things changed with review boards and lawyers being involved?

Image of Doctor handing patient prescription

Placebos are inactive substances—usually inactive—things like sugar, or starch pills that are given to people with some suggestion that they might help.

The dose response curve of most placebos is remarkably similar to aspirin, ibuprofen, or acetaminophen. It reaches maximum efficacy in 20 to 30 minutes and then it tends to trail off in its effectiveness after four to six hours.

Which Placebos Work Best?

It turns out that among placebo pills, bigger pills are more effective than smaller pills and two pills tend to be more effective than one pill.

Now active placebos are much more effective than passive placebos. An active placebo isn’t just sugar or starch, it’s some medicine that in some way causes some response in the body which is uncomfortable. So, it’s like giving somebody niacin that will make them flush, or giving them something that will give them a dry mouth—something so that the person can feel a change in the body, even if that change in the body has nothing to do with the purported effect of the placebo.

To get really effective though, it helps to move beyond pills. Injections tend to be much more effective than pills. And active injections, in other words injections of substances that change how we feel in the body, are more effective than injections of saline.

The Remarkable Power of Placebos

Let me give you some examples. One of them that dates from the ’70s involved treatment for temporomandibular joint disorder, which is pain that occurs in the joints of the jaw muscles and the jaw joint. It was thought, in the 1960s and the 1970s, that the epidemic of temporomandibular joint problems that was happening at the time were probably due to the deterioration of the joints. And oral surgeons were busy putting replacement disks into the joint. They used Teflon for example, for some of them. But the problem was that the Teflon started to deteriorate, and they had big problems.

So, one enterprising group of dentists who thought, you know, I don’t think this is about the structure of the jaw, I think this is about the patient’s attitude toward the TMJ symptoms—they decided to try an intervention called “sham tooth grinding.” And what they did was they created a dental instrument that was about an inch in diameter, and maybe six or eight inches long, that vibrated a lot.

And what they did was they told patients that they were going to realign their bite. And they would put this instrument into the patient’s mouth, and shake, rattle, and roll. They basically vibrated for some 40 or 45 minutes, after which they told the patient, we think we’ve done it. We’ve reconstituted or restructured the shape of your teeth so that you should have a better bite now, and this should resolve the difficulty. Sixty-four percent of the patients who had sham tooth grinding had total or significant relief a year after simply one application of the procedure.

Learn more: Placebos, Illness, and the Power of Belief

Solving Angina Pain

There was a common surgery that was done for angina pain. Angina pain, as you probably know, is pain that comes from partial or greater occlusion of blood vessels in and around the heart. And it’s a kind of chest pain that comes from this. And it was found that they could do something called “mammary artery ligation” to resolve this. And what they would do is the following surgery. First, they would open up the chest. They made an incision all the way from the collar bone down most of the way to the naval. Then they would saw through the breastbone, they would retract the rib cage, and they would tie off this artery, the mammary artery, and then sew people back again. And the logic behind this was that by tying off the mammary artery, you’d induce the heart to grow collateral vessels. It was kind of like creating nature’s own bypass, if you will.

And it used to work pretty well. They got 80 percent to 90 percent success rate of people recovering from angina pain with the surgery. The only fly in the ointment was that every once in a while, somebody would subsequently die—not usually from the surgery, but die from other causes. And upon autopsy, they never found the collateral vessels. So that raised the question, what’s up? What could be causing the relief from the pain?

One enterprising group of doctors thought, let’s test this more scientifically. And they took the next series of patients that came into their hospital, who were appropriate candidates for mammary artery ligation, and they did most of the surgery as usual.

They did the incision from the collar bone down, they sawed through the breastbone, they retracted the ribcage. But they didn’t actually touch the heart. They just sewed people back up again and told them that they had had successful mammary artery ligation. They then followed these patients and saw what happened once they healed. And what did they discover? Eighty to ninety percent success rates—same success rates that they had with the real mammary artery ligation.

Ethical Considerations

Now, you as a modern person may be thinking there’s an ethical problem with this. And indeed, perhaps there was an ethical problem. It’s a little hard to find this journal article. It just so happens that the journal article reporting on the surgery was published by a little publishing house that is literally just down the road from where I live in Massachusetts. The name of the journal, you’ve probably never heard of it, it’s called The New England Journal of Medicine. And it was published there in 1959 without a single mention of ethical issues. The next year, it caused quite a stir. Another team of doctors did the exact same surgery on a new group of patients, also not telling them about it. That was published in The American Journal of Cardiology in 1960.

Legal Considerations

And then the lawyers got involved. They started saying, you can’t do that. These are human beings. You have to give informed consent—which, while I’m very sympathetic to that argument, entered us into the Dark Ages. Because then, how are we to know going forward, when a surgical intervention seemed to be helpful to people and eliminate pain, or reduce pain, how could we know whether it was a placebo effect or the effect of the surgery? Frankly, we couldn’t.

Learn more: Torts: Rules versus Standards of Care

Full Disclosure

Until the year 2000, when we started coming out of the Dark Ages because of a team of enterprising surgeons and researchers at the University of Texas because they actually came up with a plan by which they could do placebo controlled surgery, and get it passed by an institutional review board, because it was an ethical plan. And here’s what they did. They took subjects and they told them in advance that they were going to be randomly distributed to either arthroscopic debridement, which meant making little incisions around the knee to do arthroscopic surgery, and smoothing out the structures under the kneecap, arthroscopic lavage, which meant washing out the structures under the kneecap, or the incisions only. That was the placebo group. And they followed these folks for two years.

The study was very well done because what happened was, the surgeons did the surgery, but then they never saw the patients again. The researchers followed them in the post-operative period, and then on over the next two years. And the researchers were completely blind to the condition. They had no idea who had had the surgery, and who had not had real surgery but only had placebo interventions.

Now, because of my interest in placebo research, and because I use it clinically to help patients understand that the mind is so powerful, and its effects on the body, I was following this study very closely. And at the end of the study, it got a lot of media attention. And I was listening on National Public Radio while they interviewed one of the subjects who had been in the study.

And this subject said that he was very glad to have participated because starting about a week or so after the surgery, once the incisions healed, he had felt much better, and he’d actually been free from knee pain for the last two years. And what he said was, “I think the surgeons were top notch because clearly they cured me. But the researchers, they were very sweet, very nice supportive people, but they weren’t as competent as the surgeons.” The reporter said, “What makes you say that?” He said, “Well, the other day, when they finished the study, the researchers got all confused. They thought I was in the placebo group.”

Everybody improved. Real surgery had no advantage over the placebo at any point during two years following surgery. This is very powerful stuff.

Acupuncture and Placebos

Let’s look at acupuncture. These effects aren’t simply limited to surgery. In 2005, there were two large, high quality trials in patients with headache. They found little difference between the effects of acupuncture and placebo acupuncture, but a very big difference between placebo acupuncture and no acupuncture at all. It turned out that placebo acupuncture was pretty much as good as real acupuncture.

Image of person receiving acupuncture on their backThen in 2002, there were 131 consecutive lower back pain patients at a university in Germany who were randomly assigned to three groups, and each group received active physiotherapy across the whole study. The control group got no further treatment. There was an acupuncture group that got 20 sessions of traditional acupuncture. And then there was a sham acupuncture group that got 20 sessions of sham acupuncture. Now, sham acupuncture is an interesting procedure. They stuck in needles, but they stuck them in superficially. And they stuck them between 10 and 20 millimeters away from the true acupoints, outside of the meridians. And, the needles weren’t simulated, as they often are in real acupuncture. They found significant improvement in traditional acupuncture for chronic low back pain compared to the routine care—the physical therapy—but no difference from sham acupuncture. Sham acupuncture also worked just as well.

Josephine Briggs is the doctor who’s the director of the National Institute for Health, the Center for Complementary and Alternative Medicine here in the United States, and she’s come to the conclusion that acupuncture is a particularly effective placebo intervention. It’s so well-designed with a whole ritual, it involves breaking of the skin—which we know works so much better than simply taking pills—it requires time, and the person has a full-body experience when they go in for acupuncture.

Knowing It’s a Placebo

Perhaps even more remarkably, we now know that placebo interventions will work even when people know that they’re getting a placebo intervention.

This is a transcript from the video series The Science of Mindfulness. It’s available for audio and video download here.

There’s a center for placebo studies in one of the Harvard teaching hospitals, and they took 80 patients who were randomized to either open label placebo pills—in other words, they were told this. They were told placebo pills are made of an inert substance, like sugar pills, and they’ve been shown in clinical studies to provide significant improvement in irritable bowel syndromes through mind-body self-healing processes. And the subjects had irritable bowel syndrome. So they thought, OK, this can work. But they were told that these are sugar pills, and they were told the truth, which is that sugar pills do help with this disorder. So they either got the placebo pills, or they were in no treatment control group that got the same quality and type of interaction with the providers, but no placebos. The people with the open label placebos had significantly higher global improvement scores on their irritable bowel syndrome symptoms at both 11 day midpoint of the study, and at the 21 day end point.

What was fascinating to me, I was following this on the radio also, was that the patients, after the study, who got the placebo pills said, “This is great. Thank you. I’m glad I participated. Where can I continue to get the placebo pills?” And the researchers said, “Well, they’re just inert. You could just use Tic Tacs.” And the subject said, “No, no, no. I want those placebo pills. Those are what worked for me.” And they’re actually upset when the researchers couldn’t provide them because there are various ethical and legal strictures that made it so that they wouldn’t do it.

Learn more: How Mindfulness Mimics The Placebo Effect

From the lecture series: The Science of Mindfulness: A Research-Based Path to Well-Being
Taught by Professor Ronald D. Siegel,Pys.D.