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What is a placebo?

In Latin, placebo means “I shall please” and have been used for centuries. Anything that is used as “real” medication but has no medical properties is called a placebo. Despite this fact, they work as good as, if not better than “actual” medical pills.

Placebos are designed to appear exactly as real medical treatments. They are generally in the form of a sugar pill or a saline solution injection.

What is the placebo effect?

While placebo refers to the inactive medicines, the term placebo effect concerns the effects that the patients have as a response to their placebo treatment. In other words, it refers to the real therapeutic healing as a result of fake drugs. 

The effect has a psychological effect than a direct physical effect on our bodies. This phenomenon reinforces the powerful influence of the mind on the body. 

Let me give you an example to clarify this phenomenon. In the Rio Olympics, many athletes were covered in circular marks caused by cupping. This is a therapy in which suction is used to increase blood flow and reduce muscle tension. In a study, some patients received cupping therapy while some received a fake therapy in which the cups had holes and could not create proper suction. The reports show that all the objects experienced the same degree of pain relief.  

What is the psychology behind the placebo effect?

It is mind-over-matter since it has been proven that one’s brain can convince one’s body that a fake treatment is real. Under the right circumstances, placebos are equally as effective as traditional medicines.

In a study in which people were told that a placebo was a stimulant, their pulse rate sped up, blood pressure increased and reaction speeds improved. When another group was told that the same medicine was to help them sleep, they experienced a decrease in pulse rate, blood pressure and reaction speeds.

Patients who highly expect a placebo to work show a better response to it. However, the response is not simply imagined by the patient.

What is the biochemistry behind the placebo effect?

Despite the role of psychology in the placebo effect, it is stemmed from more than positive thinking. 

Placebos give rise to certain changes in neurobiological signaling pathways.

Figure 1: The expectation of benefit associated with a placebo causes measureable changes in neurobiological signaling pathways, resulting in pain relief.

Figure 1: The expectation of benefit associated with a placebo causes measurable changes in neuro-biological signaling pathways, resulting in pain relief.                                                                                                          Source: http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/

If a doctor prescribes you a placebo for pain relief, your expectation for therapeutic benefits activates reward pathways in the brain. Endorphins, which are chemically similar to opiates like morphine, are stimulated and released by the brain. Such chemical compounds bind to opioid receptors and cause pain relief. 

Quite simply, your brain will use its supply of natural painkillers. 

A chemical called naloxone, which was developed to prevent overdose on opiates like morphine and heroin, can be used to negate the response. It acts by blocking key opioid receptors in the central nervous system and partially prevents the placebo effect. Hence, the placebo effect can be biochemically modulated.

Figure 2: (A) Morphine causes pain relief by binding to opioid receptors in the brain. (B) The reward pathways activated by placebos cause the release of endorphins, which bind to opioid receptors. (C) Naloxone blocks opioid receptors, preventing the binding of endorphins, thereby partially blocking the placebo effect.

Figure 2: (A) Morphine causes pain relief by binding to opioid receptors in the brain. (B) The reward pathways activated by placebos cause the release of endorphins, which bind to opioid receptors. (C) Naloxone blocks opioid receptors, preventing the binding of endorphins, thereby partially blocking the placebo effect.                         

Source: http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/

Besides the opioid system, placebos also affect other similar pathways. They increase the release and uptake of endorphins and dopamine (feel-good hormones), which are involved in reward-motivated behaviour and pain relief.

The role of genes in the placebo effect has recently been uncovered. Genetic signatures may alter the opioid and dopamine signaling pathways. So, patients who have less active opioid receptors are less likely to respond to placebos. Patients with reduced dopamine metabolism have higher dopamine levels and are therefore more likely to respond strongly to placebos.

Here are some other factors that contribute to the magnitude of the placebo effect:

  • The nature of the illness
  • The patient’s expectations and belief in the treatment
  • The positive interaction between a patient and a healthcare provider regarding the treatment’s effectiveness
  • The environment in which the treatment is received
  • The rapidly improving health systems globally also have more people relying on and believing in medical treatments. As medical technology improves, our faith in medicine strengthens.

According to studies, placebos affect the following conditions:

  • Pain
  • Depression
  • Sleep disorders
  • Irritable bowel syndrome
  • Menopause
  • Fatigue and nausea

In a recent placebo surgery, some patients underwent arthroscopic surgery for osteoarthritis of the knee while some were given only an incision and sewn up with no surgery. This research concludes that all the patients faced the same result. 

In addition to these, placebos can even display changes in the heart rate, blood pressure level, anxiety level, and brain activity of individuals. Although they can be effective in such illnesses and their side effects, they are not a cure for underlying conditions.

In a study involving asthma, placebo inhalers provided some relief but did not bring about a better result in breathing tests.

How has it been used in medical research?

In a clinical trial, people are given either placebos or real medicines. As both are made to look identical, the people do not know what kind of treatment they were given. Researchers sometimes conduct a double-blind study in which neither the participants nor the researchers know who is getting which type of medicine. Then, their response is recorded to determine the effectiveness of placebos in comparison to real treatment. They can also help ascertain the physiological and psychological effects of new medications.

During drug testing, drugs that are more effective than placebos are only approved by the Federal Drug Administration. A patient’s response to medicine should also be equivalent to the drug’s biochemical effects and the placebo effect. 

Is the placebo legal?

While prescribing a placebo is not illegal, it is considered unethical if the patient does not realize that they are getting a “fake” medicine. 

A recent survey based on Chicago shows that 45% of medical practitioners used a placebo at some point during their clinical practice. Out of them, only 4% let their patients know that they were receiving a placebo.

The fact that placebos work better when patients are unaware of the true nature of their medicines may also be a reason that healthcare providers refrain from telling them the truth. However, medical associations take a strong stance against professionals who prescribe placebos without a patient’s knowledge or consent.

What can you expect if you know that you are receiving a placebo?

A study in 2014 concluded that placebos are 50% as effective as the real drug to reduce the pain of a migraine attack when the patients knew that they were getting a placebo.

Researchers believe that the somewhat positive response is due to the simple act of taking a pill since people associate it as a positive healing effect. Even when they knew they were receiving a sugar pill, the action of taking it stimulated the brain into thinking that the body was healing.

Placebo effects are not simply responses to pills and injections. Instead, a healthy diet, exercise, yoga, and meditation are key therapeutics that lead to a placebo effect.

Over the next couple of years, multiple studies and debates on placebos are anticipated.

Citations:

Ann M. Altman Ph.D., “More Than Just a Sugar Pill: Why the Placebo Effect Is Real.” Science in the News, 14 Sept. 2016, http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/ 

DerSarkissian, Carol. “The Placebo Effect: What Is It?” WebMD, 8 Feb. 2020, https://www.webmd.com/pain-management/what-is-the-placebo-effect#2

Publishing, Harvard Health. The Power of the Placebo Effect. https://www.health.harvard.edu/mental-health/the-power-of-the-placebo-effect

“Doctors Admit Prescribing Placebos.” CNN, Cable News Network, https://edition.cnn.com/2008/HEALTH/dailydose/11/27/placebo.ethics/index.html#:~:text=Prescribing%20placebos%20is%20not%20illegal,is%20getting%20a%20sugar%20pill.

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