January 11, 2021


The History of Placebos & Why Doctors Should Use Them More Often (Jeremy Howick, Jan. 11th, 2021, National Interest)

Recently, placebo-controlled surgery trials have been used. In perhaps the most famous of these, American surgeon Bruce Moseley found 180 patients who had such severe knee pain that even the best drugs had failed to work. He gave half of them real arthroscopy and the other half placebo arthroscopy.

Patients in the placebo arthroscopy group were given anaesthetics and a small incision was made in their knees, but there was no arthroscope, no repairing of damaged cartilage, and no cleaning out of loose fragments of bone.

To keep the patients ignorant about which group they were in, the doctors and nurses talked through a real procedure even if they were performing the placebo procedure.

The fake surgery worked as well as the "real" surgery. A review of over 50 placebo-controlled surgery trials found that placebo surgery was as good as the real surgery in more than half the trials.

Honest placebos

A placebo can work even if a patient does not believe it is a "real" treatment.

In the first of the studies of open-label placebos (placebos that patients know are placebos) I know of, two Baltimore doctors by the names of Lee Park and Uno Covi gave open-label placebos to 15 neurotic patients. They presented the placebo pills to the patients and said: "Many people with your kind of condition have been helped by what are sometimes called sugar pills and we feel that a so-called sugar pill may help you, too."

The patients took the placebos, and many of them got better after having the placebo - even though they knew it was a placebo. However, the patients were neurotic and a bit paranoid so they didn't believe the doctors. After the placebo made them better, they thought the doctors had lied and actually given them the real drug.

More recently, several higher-quality studies confirm that open-label placebos can work. These "honest" placebos may work because patients have a conditioned response to an encounter with their doctor. Just like an arachnophobe's body can react negatively to a spider even if they know it's not poisonous, someone can react positively to treatment from a doctor even if they know the doctor is giving them a sugar pill.

The history of learning how placebos work

An early study investigating the inner pharmacology of placebo mechanisms is Jon Levine and Newton Gordon's 1978 study of 51 patients who had impacted molars extracted. All 51 patients had received a painkiller called mepivacaine for the surgical procedure. Then, at three and four hours after the surgery, the patients were given either morphine, a placebo or naloxone. The patients didn't know which one they had received.

Naloxone is an opioid antagonist, which means that it stops drugs such as morphine and endorphins from producing their effects. It literally blocks the cell receptors, so it stops morphine (or endorphins) from docking onto those receptors. It's used to treat morphine overdose.

The researchers found that naloxone blocked the painkilling effect of placebos. This shows that placebos cause the release of painkilling endorphins. Since then, many experiments have confirmed these results. Hundreds of others have shown that placebo treatments affect the brain and body in several ways.

The main mechanisms by which placebos are believed to work are expectancy and conditioning.

In a comprehensive study published in 1999 of conditioning and expectancy mechanisms, Martina Amanzio and Fabrizio Benedetti divided 229 participants into 12 groups. The groups were given a variety of drugs, were conditioned in a number of ways and were given different messages (to induce high or low expectancy). The study found that placebo effects were caused by both expectancy and conditioning.

Despite the progress, some researchers argue - and I agree - that there is something mysterious about how placebos work. 

Posted by at January 11, 2021 12:00 AM