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The Placebo Effect

What is a placebo?

A placebo is often thought of in terms of a sugar pill but it essentially refers to any treatment or intervention that in itself has no biological effect - e.g. a saline injection or even simulated surgery. Rituals around treatment, trust in the doctor, and belief in the treatment itself can also make patients better. It’s often said that the history of medicine is the history of the placebo effect as many traditional treatments have been shown to be ineffective.

The term comes from the Latin for “I shall please”. Once commonly prescribed by doctors, placebos are now used to test new drugs.

Is it fake?

A placebo may not contain active drug, but it is now known that it can have a real-life, physical effect. Brain scans of patients show marked changes in brain chemistry in response to placebo.

How does it work?

Placebo works through belief, suggestion and expectation (when you start to feel better in a doctor’s waiting room in anticipation of being given an effective treatment, that is the placebo effect). Placebo treatment prompts the brain to release endorphins - naturally occurring hormones that act similarly to morphine and codeine. For this reason, placebos are especially effective in pain and depression. The placebo effect may also involve the brain chemical dopamine (the neurotransmitter lost in Parkinson’s). This is one explanation why the placebo effect can be particularly marked in Parkinson’s trials (where up to 30% of improvement seen can be due to the placebo effect alone).

Would you fall for it?

If you’ve been to the doctor, it’s likely you’ve received placebo at some point. Ninety-seven percent of UK-based GPs admit to prescribing placebos over their careers, according to a 2013 survey. Doctors no longer dole out sugar pills (once a mainstay). However, it is common for doctors to prescribe a treatment (e.g. an antibiotic for a viral infection) even if they know it can’t work - to soothe a patient.

So if it’s so effective, then why not give placebos rather than real drugs?

Not all medical problems respond to positive thinking and expectation - and only one in three people respond to placebo. Dramatic effects are the exception rather than the rule and the effect is usually short-lived.

Is it ethical?

Most doctors agree that placebos have a place in medicine, but there’s disagreement on whether absolute truth is always best for patients, or whether lying is acceptable when it helps a patient get better.

Harvard researcher Ted Kaptchuk wondered whether doctors could tell patients they were receiving placebo and still see a placebo effect. Kaptchuk conducted the first open-label placebo trial, wherein patients knew they were getting placebo. He studied 80 adults suffering from irritable bowel syndrome. All participants were explicitly told that the placebo pills did not contain any medication. Even so, 60% of open-label patients obtained “adequate relief” for IBS on a standardised questionnaire compared with 35% for no treatment.

Placebo Timeline

  • 1747: First placebo-controlled study. Scurvy used to kill more sailors than storms, shipwrecks and combat combined. In 1747, James Lind, a ship’s doctor, tests various treatments on sailors with scurvy. Some men get gallons of seawater to drink, or must eat vinegar or mustard. Within a week, the men given citrus fruits to eat are back on their feet. In 1795, the Admiralty makes lemon juice a mandatory addition to a diet that consists mainly of biscuits, rice, salt pork, and dried fish.
  • 1884: First “blinded” medical trial. The Académie Française tests “animal magnetism”, a leading theory of the times. A “magnetist” with a metal rod is able to induce hysterical fits in a patient but attempting the same while behind a curtain, does not produce any effect. The study shows the power of suggestion and ritual.
  • 1943: First double blind, placebo-controlled trial in the UK (and the world) conducted to test a drug called patulin for the common cold. Findings on patulin were inconclusive, but by the mid-1950s, placebo-controlled, randomised trials had become the norm.
  • 1959 and 1960: First use of blinded placebo controls to evaluate surgical procedures. Two randomised, controlled trials demonstrate that surgery tying off the mammary artery was no better than a sham intervention in the treatment of angina.

Did you know...?

In the 1940s, it was so common for doctors to prescribe placebos that catalogues contained placebo pills of different colours and sizes to order.

Remarkable Results on Placebo

  • In Texas, a 2002 study by Dr. Bruce Moseley tested the power of placebo in 180 patients with knee pain. Patients with moderate osteoarthritis who underwent a placebo surgery improved just as much as those who underwent the real surgery.
  • A 2008 meta-analysis testing leading antidepressants against placebo concluded that there was no statistically significant difference between the two. A 2018 study of 522 clinical trials showed nearly the same findings: that antidepressants have a “mostly modest” effect. Despite very similar study findings, headlines about the two studies differed wildly. Articles from the earlier study bore titles like, “Antidepressants ‘no better than dummy pills’” while recent ones proclaimed, “It’s Official - Antidepressants Work”.
  • You can placebo yourself into drunkenness. In a 2003 study, subjects given tonic water and told they were drinking vodka and tonic performed worse on memory tasks.
  • A Japanese medical journal from 1962 contains a study on 13 boys hypersensitive to the leaves of the Japanese lacquer tree, which contains an irritant similar to poison ivy. The researchers touched the students on one arm with harmless leaves but told them that these were poisonous; they then touched the students on the other arm with the poisonous leaves but told them that the leaves were harmless. All 13 boys broke out in rash in response to the harmless leaves. Only two reacted to the poisonous leaves.
  • For patients with chronic fatigue syndrome, fibromyalgia, and rheumatoid arthritis, placebo had effects comparable to those of morphine, according to a 2017 study in PAIN Practice.

Nocebo: Placebo’s “Evil Twin”

Negative expectations can cause unpleasant symptoms in the absence of a physical cause. Sham pills or treatments can make people worse if they are expecting adverse effects. Nocebo means “I shall harm”.

  • An individual in a 2007 trial attempted to commit suicide by swallowing 26 antidepressant pills. Unknown to him, they were sugar pills. Still, the man experienced dangerously low blood pressure, and required IV fluids.
  • In a 2010 study testing drugs to treat cancer fatigue, more than 50% of the placebo group experienced negative side effects. Nearly 80% reported insomnia, more than 50% had anorexia, and 38% reported nausea.
  • More than 42% of patients receiving a placebo control in 2011 preventative treatment studies for tension-type headaches reported adverse side effects. Nearly 5% dropped out because of negative symptoms.
  • A 2004 paper observed 600 patients from three drug allergy clinics. Patients received either the drug causing their adverse reactions, or a dummy pill. Twenty-seven percent of patients experienced side effects such as itching, malaise and headache from the placebo.
  • Volunteers were told that a (nonexistent) electrical current would pass through their heads, possibly causing a headache. Two-thirds of them developed a headache.
  • Patients with asthma were divided into two groups. One was given a bronchoconstrictor, which ordinarily makes asthma symptoms worse, and told that it was a bronchodilator, which normally improves the symptoms. The placebo suggestion reduced their discomfort by more than 40%. A second group was given a bronchodilator and told it was a bronchoconstrictor. The nocebo suggestion reduced the drug's effectiveness by nearly 50%.