Is The Placebo Effect Real (Can It Be Negative)?

— Researched and written by Dr. Sandip Roy.

Research shows placebo pills can help create lasting behavior change by tapping into societal expectations. Find out if the placebo effect is real.

Desperate, terminally alive, sad people turn to expensive placebos for a chance to imagine a decent life. ― Sarah Perry, Every Cradle is a Grave

A placebo is a dummy pill, which means it has zero medicinal effect. So, has an empty pill kept us happy for over two thousand years?

We explore the fascinating story of placebo effects — and it’s a long, interesting story.

Read on to find out if your mind is capable of healing your body. Find out if plain sugar pills can have real biological effects, almost as good as prescription drugs.

Are Placebo Effects Real?

Yes. Placebo effects can be real, even though a placebo is a “dummy pill” with no pharmacological effect. It may have an effect on a person who believes they are taking a medicine. However, the ingredients of a placebo cannot explain the beneficial or negative effects because they have not been found to have any therapeutic or adverse effects in trials.

Placebos have been used for centuries by both physicians and quacks to help patients get over many diseases, through deception. Treatment by placebo is deception, as the contents in the placebo do not carry any medicinal properties.

But new research is proving otherwise — that a placebo can indeed have a clinically diagnosable, valid effect on us.

Research is proving these pills, far from being fake or sham, have actual effects.

In fact, 30 to 40 percent of the people given a placebo have shown improvement in their symptoms.

A placebo is an object that is falsely presented as a “genuine” medical therapy, although it does not contain any active substance that can affect the health of the taker.

It could be a pill, an injection, or some other “false” treatment as a rendered or shared belief. In Latin, placebo means, ‘I shall please!’

So, is it time to revise the whole story of the placebo?

How Placebo Effect Occurs?

Placebo effects occur because the person taking the placebo believes it is a medicine that will relieve their symptoms. Researchers have found that placebo pills can have effects on people even after they have been informed that the contents of the pill have no known effects. It may be assumed that such people believed that their bodies caused the placebo to act.

Placebos pills are given for relieving the symptoms of an illness, but contain nothing of proven medicinal effect. So, a placebo pill is actually an empty pill of happiness.

True placebos are pills given to consenting people with full, partial, or even false information, or just without any knowledge of the pills’ ineffectiveness.

They fall within the category of placebo as long as the contents are known to be safe and inert. Scientists call these non-deceptive placebos.

In a 2010 study called Placebos Without Deception at Harvard Medical School, Kaptchuk and others gathered patients with Irritable Bowel Syndrome (IBS). While one group received no treatment, another group was told they would be given inactive drugs.

To clarify it for all, these inactive drugs were placed in bottles labeled “Placebo Pills.”

When the results came, it was found that patients who knew they were taking placebos reported twice as much relief as the other group. The placebo had healing effects as good as some of the best real IBS drugs.

“Our results challenge ‘the conventional wisdom’ that placebo effects require ‘intentional ignorance,’” they wrote.

Thus, the concept of open-label placebos or ‘honest placebos’ was born. However, the FDA doesn’t legitimize prescription placebos.

A July 2020 paper in Nature found that non-deceptive placebos are viable emotion regulation tools, and they take some time to reduce negative emotions.

Moreover, at least for emotional distress, non-deceptive placebos lead to genuine psycho-biological effects and are more than response bias.

In their research, a team led by Darwin A. Guevarra of Michigan State University carried out two experiments.

• In experiment 1, participants who were educated about the placebo effects and then received a non-deceptive placebo nasal spray reported less emotional distress when viewing emotional images.
• In experiment 2, participants who received the same non-deceptive placebo intervention showed reduced activity in a neural marker of emotional distress when viewing emotional images.

Dr. Guevarra says,

I hope these findings bring us closer to using non-deceptive placebos as mainstream interventions. They have the potential to regulate daily emotional life and help manage distress that accompanies many physical and psychiatric conditions.

Research shows a placebo acts, even when you know they are just useless.

Most Likely Used As A Placebo: A (Somewhat Disgusting) History

Placebos are not entirely the domain of pills or drugs—they can come in many forms. A placebo can be pharmacologic (as a tablet), physical (as a manipulation), or psychological (as a conversation).

History has evidence that placebos came as

• magic,
• lotions & oils,
• religious rites,
• exorcism rituals,
• phlebotomy or bloodletting,
• emetics (potions that made one vomit),
• purgatives (potions that made one evacuate their bowels),
• suppositories (small, round, conical objects inserted into body orifices like anus and vagina).

And even urine, menstrual blood, many kinds of feces (of human and animal origin), and physical and psychic torture.

Incidentally, bloodletting was the longest-lasting sham treatment of our times; and according to some medical historians, it was this that killed George Washington.

Menstrual fluids, feces, urine, and bleeding out were historically used as placebo treatments.

Some of these archaic placebo treatments still reign today in some parts of the public in every country throughout the world, despite being unscientific in the modern world.

A commonplace placebo used even today by some in the villages and suburbs of India is to make the person who faints—hold your nose—smell a dung-smeared shoe.

Hippocrates, the Father of Medicine, was apparently a placebo dispenser. The benefits that his patients derived were mostly the result of the ‘patient-doctor relationship’ – the placebo effect.

All the ‘healers’ among the Babylonians, Greeks, Egyptians, Romans, and Chinese, worked their charms by the same placebo effect.

The Indian medicine system was an evolved one in those times; and even though they correctly used turmeric paste for wound antisepsis and ant-heads for closing surgical lacerations, prescriptions of fasting, abstinence, and cow-dung served the purpose of placebo in those times.

Historically, until the mid-20th century, almost all medicines given by doctors in the Western system were placebos.

However, the practice did not end after that. Placebo pills still have a place in modern medicine, albeit in a much different—and scientific—way.

Placebo-Controlled Trials: Placebo or Active Agent?

The placebo effect is a fascinating yet puzzling phenomenon. It has challenged the investigators for over 60 years.

Researchers have used placebos in drug trial studies to find out whether the pharmacological effects of a drug are real or fake.

In placebo-controlled trials, a new drug is given to a “test” group, while a placebo is given to the “control” group, and then the results are compared. If the effect is seen in the test group but not in the control group, then the effect is real.

However, the challenge arises when both groups show the same positive or negative (adverse) effects. It becomes more complicated when some members of each group report unexpected results.

Researchers usually conduct a double-blind, randomized, placebo-controlled trial to be completely neutral in influencing the reported effects.

The pharma research community regards this double-blind trial as The Gold Standard for proving the efficacy of a potential new medicine. The term “double-blind” refers to the fact that both the patients and the researchers are unaware of which pill (real or dummy) the patient had received.

Is Placebo A Treatment Or A Faith Reflex

The placebo effect or placebo response can simply be described as an effect produced by a placebo. It can be an actual or imagined relief of the symptoms of a medical condition after having a fake pill. Essentially, a placebo effect is a psychosomatic effect – an unconscious, automatic response of the mind-body combination.

Guess and Engel, in The Science of Placebo, define the placebo effect as:

The positive physiological or psychological changes associated with the use of inert medications, sham procedures, or therapeutic symbols within a healthcare encounter.

One area of the placebo effect that has been extensively researched is placebo-induced pain relief, called placebo analgesia — the study of the neurobiological mechanisms of pain reduction by placebo.

Even though medicine has evolved enormously over the last two millennia, however, the placebo effect remains a pervasive phenomenon even today. Until the middle of the 20th century, it was primarily the faith of the patients in their doctors that treated them for over 2,000 years.

Every concoction handed by the doctor had an invisible order written into it, ‘This will heal you!’ Faith was the only actively beneficial ingredient in those medicinal mixtures.

As Walter Brown writes,

The history of medical treatment is largely a chronicle of placebos.

A Danish study of 772 randomly selected general practitioners revealed that 86% of them admitted to using a placebo for their patients at least once, and 48% said they used it over 10 times, over the last year.

A typically used placebo intervention was dispensing antibiotics for viral infections. The most reported reason given by the clinicians was that they gave it to avoid confrontation with the patients.

Unsurprisingly, when patients have been conditioned to believe that their doctors will undoubtedly treat them for their ailment, they got better relief with placebos.

Good behavior by doctors has also been found to influence better therapy responses.

The warmhearted doctors have been the placebos themselves – since the beginning of medicine.

In a study, the placebo response increased from 44% to 62% when the doctor treated their patients with “warmth, attention, and confidence.”

These prove one thing: The doctor himself is a placebo.

However, even when placebos can have noticeable effects, it’s not too much. Two Dutch doctors, Asbjørn Hróbjartsson and Peter C. Gøtzsche carried out a systematic review of 130 clinical trials in which patients were randomly assigned to either placebo or no treatment. They found “little evidence that placebos, in general, have powerful clinical effects.”

Can Placebo Effect Be Negative: The Effects of Nocebos

The opposite effect of placebo is nocebo, a term coined by Kennedy in 1961. The nocebo effect gets activated with negative expectations, but appears to be caused by conditioned reflexes.

In nocebo, a negative outcome occurs because of the belief that the intervention will cause harm. Nocebo in medicinal reactions implies patients are more likely to experience adverse effects if they expect an adverse effect. Often, these are clinically diagnosable.

Nocebo in Latin means “I shall harm”.

The placebo pills are also capable of causing negative side effects — “nocebo effects.” A patient can develop severe reactions after taking a placebo.

Some people are more prone to nocebo effects, such as women, patients with anxiety and depression, pessimistic personalities, and those heavily influenced by their environment. They frequently require counseling to avoid triggering the nocebo effect.

Groundbreaking Placebo Researches

The area of placebo effect that has been extensively researched is the one of placebo-induced pain relief, called placebo analgesia — the study of the neurobiological mechanisms of pain reduction by sham therapy.

It is now known that placebos reduce pain by causing the release of the body’s natural endorphins, and changing the threshold of pain perception. Researchers have also shown individuals high in optimism show a greater placebo analgesic response.

Perhaps the first investigation into the mechanism of the placebo effect was carried out by L. Lasagna and colleagues at the Massachusetts General Hospital in Boston in 1953.

They did a two-part study on a total of 162 patients who had undergone surgeries and concluded that out of the 69 patients who received placebo injections for pain reduction, 11% showed a ‘consistent’ response, while 55% showed some response.

Henry K. Beecher, an anesthesiologist and a colleague of Lasagna, authored a classic paper called The Powerful Placebo, which examined 15 existing clinical reports with placebo responses. These studies had data from 1,082 patients in whom, Beecher suggested, placebo showed significant effectiveness in approximately 35%.

35% of people show effects on taking placebos. 75% of Antidepressant benefits are placebo effects.

Two of the foremost placebo researchers in the world today are Ted Kaptchuk and Fabrizio Benedetti.

Ted Kaptchuk, a professor of medicine at Harvard Medical School, holds the position of the Director of the Harvard-wide Program in Placebo Studies and the Therapeutic Encounter (PiPS). In two fMRI-aided brain studies published in the Journal of Neuroscience in 2006 and 2008, Ted Kaptchuk and his team showed that placebo treatments alter the areas of the brain that regulate pain reception.

Fabrizio Benedetti, a professor of physiology and neuroscience at the University of Turin Medical School, Italy, is widely regarded for his research into the placebo effects, he is said to run “the foremost laboratory for the study of placebo effects in the world.”

Benedetti is convinced by his studies that “therapeutic rituals move a lot of molecules in the patients’ brain, and these molecules are the very same as those activated by the drugs we give in routine clinical practice.” That is, ritualistic practices and medicinal drugs have similar effects on our brains at the molecular levels.

However, some studies also point out the ineffectiveness of placebos in certain conditions.

In a paper published in The Journal of Pain that meta-analyzed data from 340 participants, Gashirai Mbizvo and his research team concluded that in cases of Complex Regional Pain Syndrome (CRPS), placebo analgesia does not last beyond the initial 15-30 minutes.

Are Antidepressants As Good As Placebo Pills?

The question above may sound rhetorical, but placebos have been shown to be almost as effective as antidepressants. It may come as a surprise to you that brain images reveal placebo-treated patients have the same changes in their brains as those treated with prescription drugs.

• A 1998 meta-study of 2318 patients showed that 75% effectiveness of the antidepressants is due to the placebo and other non-specific effects. That is, placebos can be 75% as effective as antidepressants.
• Martin Seligman in a widely cited chapter titled Positive Psychology, Positive Prevention, and Positive Therapy, quoted the above study and wrote: “In the depression literature, a typical example, around 50% of patients will respond well to placebo drugs or therapies. Effective specific drugs or therapies usually add another 15% to this, and 75% of the effects of antidepressant drugs can be accounted for by their placebo nature.”
• A 2002 meta-analysis of the FDA database by Antonuccio and Burns, in a paper titled “Antidepressants: A Triumph of Marketing Over Science,” concluded that many of the widely prescribed antidepressants have a clinically negligible advantage over placebo.
• A 2009 article in NEJM (New England Journal of Medicine) that reviewed Herzberg’s Happy Pills in America, Tone’s The Age of Anxiety, and Shorter’s Before Prozac, suggested that the antidepressant class of SSRIs, which include Prozac, have no advantage over the largely discarded tranquilizers Librium and Valium.
• NEJM proposed that the pharmaceutical industry has replaced these, as well as the superior TCA and MAOI class of drugs, with the SSRIs simply because the latter are on-patent and thus more profitable.

FAQ

Final Words

If placebo means ‘I shall please,’ then, isn’t happiness a placebo effect after all?

Yes. And No.

1. Yes: Happiness could be the effect, of which a placebo may be the cause.
2. No: Placebos can have a ‘nocebo’ effect – which gives unhappiness.

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√ Also Read: 5 Key Principles of Positive Psychology (Happiness Science)

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