The Placebo Effect

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“The bicycle breaks screeched as I took a hard right turn toppling down on the tar road. The scratches in my 5-year-old feet cried, calling her in pain! She approached and took my feet in her arms, and with a smiling face she said: “Everything is okay my son”. The pain faded away.”


Pain can be described as a complex phenomenon that can have different aspects as physical, emotional, social, and spiritual. It is universally common but an identical and subjective experience. Our mind playing a powerful role in the above scenario, can either make us feel better or make us feel worse. The science behind this fascinating incident can be explained with the “Placebo Effect”.

The history of the placebo effect

“The placebo effect is a psychobiological phenomenon that can be attributable to different mechanisms, including the expectation of clinical improvement and pavlovian conditioning.“

Fig.1: Placebo as medicine?

Simply a “placebo” is a medically inert substance given to a patient as if it were an effective medicine. The word “placebo” means “I shall please” in Latin.

In the late 90s, a study was conducted to test a new pain killer on a set of volunteers. The pain killer was applied to the index finger of one hand of each subject. Then a certain physical pain was induced to the index fingers of both hands. Most of the subjects reported that there was less pain in the index finger where the pain killer was applied. Obvious isn’t it?

Nevertheless, the so-called pain killer was a sham that had no pain-relieving properties. Yet the subjects reported otherwise. This application is a “placebo”, which was believed to have an effect on altering the subject’s perception of pain.

Fig.2: Placebos resembles the real drug being medically inert.

During the 1700s, fake medicine was administered to patients when there were no real medicines discovered. In some instances, those had worked miraculously making the patients feel better for some illnesses.

Fig.3: Higher the pharmacologic effect, higher the effectiveness of the drug.

By the 1950s, researchers used placebos in clinical trials. In testing new drugs with test subjects, some get the real drug and some get the placebo which is similar to the drug without the medical property. If the subjects who received the actual new drug show a significant benefit relative to those who received the placebo, the drug was considered to be effective.

Neurobiology of placebo effect

Fig.4:  Theoretical model of issues impacting the development of expectancy and how brain outputs may produce a placebo effect.

The placebos have to mimic the real treatments in order to be convincing as of the real medicine. Sugar pills, water-filled injections, fake machines, and even sham surgeries were included in the development of this study. It has shown that a pill within a fancy cover with fancy brand names is more effective than a loose pill, where both are placebos. Furthermore having a comforting chat with the doctor before receiving a placebo too increases its effect.

A systematic review done on the perceived effect of drugs and their effectiveness showed the importance of pill color, which goes the same for the respective placebos.

Fig.5: The color of the pill maters.

It is natural that people get better. But the effect of placebo is not merely a psychological trick, but an induction for an actual set of biochemical reactions in our body. They can stimulate our brain to release endogenous opiates (own natural pain killers) such as opioids and they can improve certain symptoms in Parkinson’s patients by releasing dopamine.

Fig.6: Events that might take place in the brain after placebo administration. Placebo administration might reduce pain through opioid and/or non-opioid mechanisms via expectations and/or conditioning mechanisms.

FMRI scans prove that the administration of placebo can light up the prefrontal cortex that handles complex behavioral patterns and planning, which in turn stimulates other brain regions to produce chemicals such as dopamine, oxytocin, and opioids. The placebo increases the production of these chemicals which ultimately signals the spinal cord to release their effects. The endorphins produced with the intake of placebos stop pain signals from reaching the brain.

The nocebo effect

Studies reveal that saying to a patient that your pain will worsen in time can actually lead to it. Simply a non-painful touch can be made to be painful by simply saying it will be. Searching for side effects of diseases can make them induced in our bodies as they simply affect the brain. This summarizes the opposite of the placebo effect, the nocebo effect. It is a harmless substance or treatment that may cause harm or worsen the patient’s symptoms as the patient thinks or believe that they may occur or expects them to occur. Simply letting a teasing friend saying your pain will worsen may actually make it happen.

Fig.7: Correlation between subjective report (italics), arm rigidity (black circles), and subthalamic nucleus neuronal frequency discharge (bars) in two representatives Parkinson’s disease patients. The black arrow indicates the administration of the placebo. Graph (a) shows the positive effect and (b) shows the effect on the patient’s view.

A pain not felt can be painful.

Pain, fever, stress, and nausea are not actually illnesses, but rather a series of reactions as a defense to illnesses. In the scenario of getting hurt after falling, the pain prevents the injured from making the wounds worse. It also helps them to administer germ killers to prevent a risk of serious infection. Even the presence of a fever is a sign for the patient to seek medical advice and specific treatments. But, working through the pain can lead to other issues in life and that is where the placebos come to play. Nevertheless, giving fake medicine instead of an effective treatment hinders the ethics of medicine, which may even worsen the patient’s situation. It has been recorded that different people, respond to placebos at different levels, owing to their psychology.

Belief + Treatment = Cure

Placebos have long proved that they play a major part in treatment for some diseases and effects by bringing together the factors related to trust and dumping anxious thoughts. It has to be noted that placebos cannot shrink tumors or cure wounds. Even though there is a lot to be discovered on the placebo effect, the so far proven scientific data are promising in relieving the countless mysteries of our brain. It is truly fascinating to know there is scientific reasoning for the belief that lies along with treatment, which is actually the cure for almost everything.

Fig.8: Finding the inner pharmacy.

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References: 

  1. Paul Arnstein, PhD, RN, FAAN,* Kathleen Broglio, ANP-BC, ACHPN, CPE,† Elsa Wuhrman, MS, FNP, BC,‡, and Mary Beth Kean, DNP, ACNS-BC§, 2011, “Use of Placebos in pain management”, American Society for Pain Management Nursing.
  2. Buken E. “Placebo and Placebo Effect in Clinical Trial” (The Role of Placebo in Clinical Trial), 39th ISHM Congress (39th International Congress on the History of Medicine), Bari, Italy, Proceedings book pg: 149-160, Edit. By: Alfredo Musajo – Somma, 5-10 September 2004, Oral presentation.
  3. Barry S. Oken, “Placebo effects: clinical aspects and neurobiology”, Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA.
  4. https://donovanmedical.com/hair-blog/placebo-pill-color-matters
  5. https://www.jneurosci.org/content/25/45/10390
  6. https://www.physics.smu.edu/pseudo/Placebo/Placebo.pdf
  7. https://www.howitworksdaily.com/the-placebo-effect/

 

 
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