Plato’s cure for headaches prescribed a certain leaf. But also a spell that accompanied the remedy and if one pronounced the spell at the time of its application, the remedy would cure you perfectly but without the spell, the blade had no efficacy. we would call that “spell” of the Plato recipe a placebo . Placebos have been around for thousands of years and are the most studied treatments in the history of medicine. When your doctor tells you that the medicine you take has been shown to work, it means that it has been shown to work better than a placebo. Every tax or insurance dollar that goes into a proven treatment works because it is (or is supposed) better than a placebo.
Despite their importance, doctors cannot use placebos to help patients (at least not officially) and there are debates about whether we still need them in clinical trials. However, the science of placebos has evolved to the point where our views should have changed our prejudice against them in practice, as well as the privileged position of placebo controls in clinical trials. In this journey through the history of placebos, I will show the progress that has been made and suggest where knowledge of placebos might go shortly. From pleasant prayers to pleasant treatments the word placebo as used in medicine, was introduced into the Latin translation of the St. Jerome’s Bible from the fourth century. Verse 9 of Psalm 114 was written Placebo Domino in regione vivarium. Placebo means I will please, and the verse then said, I will please the Lord in the land.
Historians will be eager to point out that this translation is not entirely correct. The Hebrew transliteration is iset’halekh liphnay Adonai b’artzot hakhayim, which means: “I will walk before the Lord in the land of the living.”I think historians are making a lot of noise about something insignificant: why would the Lord want to walk with someone who was not nice? Still, discussions continue about what placebos really are. At that time, and even today, a mourning family provided a feast for those attending the funeral. Because it was a free banquet, distant relatives and this is the important point people pretending to be relatives attended the funeral chanting placebo just to get the food. This deceptive practice led the English philosopher Geoffrey Chaucer to “Flatterers are the devil’s chaplains, always singing Placebo.
Chaucer also named one of the characters in The Merchant’s Tale” Placebo. The protagonist of the tale is January, a wealthy old gentleman who wishes to associate with a younger woman named Mary. To legitimize his desire, consider marrying her. But before making your decision, consult your two friends, Placebo and Justinius. Placebo wishes to win the gentleman’s favor and approves of Januarie’s plans to marry May. Instead, Justinius is more cautious and quotes the words of Seneca and Cato, who preached virtue and caution when choosing a wife. After listening to them both, January tells Justinius that he doesn’t give a damn about Seneca he’s marrying May.
The subject of deception also comes up here, because January is blind and does not see that May is deceiving him. In the 18th century, the term placebo moved into the medical realm when it was used to describe a doctor. In his 1763 book, Dr. Pierce describes a visit to his friend, a lady who is ill in bed. He finds a Doctor Placebo sitting next to him. Dr. Placebo had impressive long curly hair, dressed fashionably, and carefully prepared his medication at the patient’s bedside. When Dr. Pierce asks his friend how the patient is doing, she responds Pure and fine, my old friend the doctor just treated me with some of his good drops.
Pierce seems to hint that any positive effect Dr. Placebo had was due to his excellent bedside behavior, rather than the actual content of the drops.Over time, the word “placebo” began to be used to describe treatments. To my knowledge, the Scottish obstetrician William Smellie (in 1752) is the first person to use the term placebo to describe a medical treatment. It will be convenient to prescribe some innocent placemats, to be taken between moments, to fool time and please your imagination. The placemat is another form of the word placebo. Placebos in clinical trials Placebos were first used in clinical trials in the 18th century to discredit healers.
This is paradoxical because the so-called “no-healers” cures at the time included bleeding and feeding patients the undigested material from the intestines of a goat. These treatments were considered so effective that no trials were needed. The first example I know of where a placebo was used as a control was in a “Perkins tractor” test. In the late 18th century, an American physician named Elisha Perkins developed two metal rods that he claimed conducted what he called electrical pathogenic fluid out of the body. He received the first medical patent, issued under the United States Constitution, for his device in 1796.
Tractors were very popular, and George Washington is even said to have bought a set. They came to the UK in 1799 and became popular in Bath which was already a healing center due to its natural mineral waters, and associated spa which have been used since Roman times. Dr. John Haygarth however, thought the tractors were nonsense and proposed testing their effects in a trial. To do this Haygarth manufactured wooden tractors that were painted to look identical to Perkins metal tractors. But since they were made of wood, they couldn’t conduct electricity. In groups of ten patients, five treated with real tractors and five with dummy tractors the placebo tractors performed as well as the real ones. Haygarth concluded that the tractors were not working.
Interestingly, the trial did not show that tractors did not benefit people, just that they did not produce their benefit through electricity. Haygarth himself admitted that the fake tractors worked very well. He attributed this to faith. In other early examples of placebos as controls, the effects of homeopathy tablets were tested compared to bread pills. One of these early trials revealed that doing nothing was better than homeopathy and allopathic medicine. In the mid-20th century, placebo-controlled trials were frequent enough that Henry Knowles Beecher produced one of the first examples of a systematic review that estimated how powerful placebo was.
BEECHER SERVED IN THE UNITED STATES ARMY DURING WORLD WAR II.
While on the front lines in southern Italy, morphine supplies were running low and Beecher reportedly saw something that surprised him. A nurse injected a wounded soldier with salt water instead of morphine before an operation. The soldier thought it was real morphine and did not seem to feel any pain. After the war, Beecher reviewed 15 placebo-controlled trials of treatments for pain and other ailments. The studies involved 1,082 participants and found that overall, 35% of patients’ symptoms were relieved by placebo alone. In 1955, he published his study in his famous article The Powerful Placebo (The Powerful Placebo).
In the 1990s, researchers questioned Beecher’s estimates, based on the fact that people who improved after taking the placebos could have recovered even if they had not taken the placebo. In philosophical parlance, the possible wrong inference that the placebo caused the cure is called the post hoc ergo propter hoc fallacy (after, therefore due to).To test whether placebos really make people better, we have to compare people who take placebos with people who don’t get any treatment. Danish medical researchers Asbjørn Hróbjartsson and Peter Gotzsche did just that. They conducted trials with three groups of participants that included active treatment, placebo control, and untreated.
Then they checked whether giving the placebo was better than giving nothing. They found a small placebo effect that they said could have been the result of bias. They concluded that there is little evidence that placebos, in general, have powerful clinical effects, and published their results in an article titled Is Placebo Powerless? In direct contrast to the title of Beecher’s paper. However, Hrobjartsson and Gotzsche corrected Beecher’s mistake but produced his mistake. They included everything labeled placebo in a trial for any disorder. Such a comparison of apples and oranges is not legitimate.
IF WE LOOK AT THE EFFECT OF ANY TREATMENT FOR ANY CONDITION AND FIND A SMALL AVERAGE EFFECT, WE CANNOT CONCLUDE THAT THE TREATMENTS WERE NOT EFFECTIVE.
I exposed this error in a systematic review, and it is now widely accepted that just as some treatments are effective for some things but not all, some placebos are effective for some things, especially pain. Placebo surgery recently, placebo-controlled trials of surgery have been used. Perhaps the most famous of these is that of the American surgeon Bruce Moseley who found 180 patients who had knee pain so severe that even the best medications did not work. He gave half-real arthroscopy and half placebo arthroscopy. Patients in the arthroscopy placebo group were administered anesthetic and had a small incision made in their knees, but there was no arthroscope, no repair of damaged cartilage, and no cleaning of loose bone fragments.
So that the patients did not know which group they were in, the doctors and nurses explained the procedure step by step as if it were real, even if they were performing the placebo procedure. The sham surgery worked just as well as the real surgery. A review of more than 50 placebo-controlled surgery trials showed, in more than half of the trials, that placebo surgery is as good as real surgery. Patients in the arthroscopy placebo group were administered anesthetic and had a small incision made in their knees but there was no arthroscope, no repair of damaged cartilage and no cleaning of loose bone fragments. So that the patients did not know which group they were in the doctors and nurses explained the procedure step by step as if it were real even if they were performing the placebo procedure.
THE SHAM SURGERY WORKED JUST AS WELL AS THE “REAL” SURGERY.
A review of more than 50 placebo-controlled surgery trials showed, in more than half of the trials, that placebo surgery is as good as real surgery. They gave patients the placebo pills and said, Many people with your type of condition have benefited from what is sometimes called sugar pills and we think a so-called sugar pill can help you too.
The patients took the placebos and many of them improved afterward, even though they knew it was a placebo. However, the patients were neurotic and a bit paranoid, so they did not believe the doctors. After the placebo made them better, they thought the doctors had lied and given them the real drug. More recently, several better quality studies confirm that open-label placebos can work. These honest placebos can work because patients have a conditioned response to an encounter with their doctor. Just as the body of an arachnophobic can react negatively to a spider even if it knows that it is not poisonous, a person can react positively to a doctor’s treatment even if he knows that the doctor is giving him a sugar pill.
The history of learning how they work early study investigating the internal pharmacology of placebo mechanisms is that of Jon Levine and Newton Gordon in 1978 with 51 patients who had embedded molars removed. All 51 patients received a pain reliever called mepivacaine for the surgical procedure. Then, three to four hours after surgery, the patients received morphine a placebo or naloxone.
THE PATIENTS DID NOT KNOW WHICH ONE THEY HAD RECEIVED.
Naloxone is an opioid antagonist, which means that it stops drugs like morphine and endorphins from working. It literally blocks cell receptors, thus preventing morphine (or endorphins) from attaching to those receptors. It is used to treat morphine overdose. The researchers found that naloxone blocked the pain-relieving effect of placebos. This shows that placebos cause the release of pain-relieving endorphins. Since then, many experiments have confirmed these results. Hundreds of others have shown that placebo treatments affect the brain and body in various ways. The main mechanisms by which placebos are believed to work are expectation and conditioning. a comprehensive study published in 1999, Martina Amanzio and Fabrizio Benedetti divided 229 participants into 12 groups.
The groups were administered a variety of medications, conditioned in various ways, and given different messages (to induce high or low expectation).The study found that the placebo effects were caused by both expectation and conditioning.Despite the progress, some researchers argue, and I agree, that there is something mysterious about how placebos work. In a personal communication Dan Moerman, a medical anthropologist and ethnobotanist explain it better than I can
We know from all the people who do MRI that it’s pretty easy to see what’s going on inside the amygdala, or whatever other part that might be involved, but what moves the amygdala, well, that takes some work.”History of placebo ethics accepted opinion in clinical practice is that placebos are unethical because they require deception. This opinion has yet to fully take into account the evidence that we don’t need deception for placebos to work. The history of the ethics of placebo controls is more complex.
Now that we have many effective treatments, we can compare new treatments with proven therapies. Why would a patient agree to enroll in a trial comparing a new treatment with a placebo when they could enroll in a trial of a new treatment compared to a proven one? Doctors participating in these trials may be violating their ethical duty to help and avoid harm. The World Medical Association initially banned placebo-controlled trials when a proven therapy was available. However in 2010, they changed this position and said that sometimes we need placebo-controlled trials even if there is a proven therapy. As the arguments supporting placebo-controlled trials are being questioned, there is now a movement urging the World Medical Association to make another U-turn, back to its original position.
WHERE DOES THE PLACEBO GO?
For centuries, the word placebo was closely related to deception and complacency for people. Recent studies of open-label placebos show that they don’t have to be misleading to work. In contrast studies of placebos show that they are not inert or invariable and the basis for the current position of the World Medical Association has weakened. The recent history of placebos appears to pave the way for more placebo treatments in clinical practice and fewer in clinical trials.