Is placebo a trick of the mind?

The most recent works find impact at the molecular level
TEXCOCO, Mexico.- (ALIANZATEX) .- Everyone knows the placebo effect, which makes something that is not a medicine, or exercise any therapeutic action, have a measurable effect on health. Its official study began in the year 1800 when the British doctor John Haygarth published a book with the eloquent title of Of the Imagination as a Cause and as a Cure of Disorders of the Body (of the imagination like the cause and the cure of the disorders of the body) in which the first systematic study of the healing capacity of methods without therapeutic value is made.

More than 200 years later, little else we know about the placebo. During these two centuries it has been used systematically as a control tool to determine the efficacy of thousands of drugs, but the effect itself has received little attention.

The experiment of the miraculous rods

Haygarth was interested in this phenomenon due to the curiosity that gave rise to a treatment that in his time was raging. The first patent granted by the US government once independence was achieved was for a device invented by Elisha Perkins called Tractor, which consisted of a metal rod made from a secret alloy that was able to absorb pain by rubbing on the area where the discomfort was felt. In the United States it devastated and its success was such that the son of Perkins abrió a delegation in Great Britain, where each unit sold by 5 guineas (currency that was manufactured with about seven grams of gold and whose original value was equivalent to a pound sterling) , a fortune for the time.

Haygarth bought a Tractor, made a similar one of metal, without being of the secret alloy, and another one of wood that painted of metallic color to give him the appearance of metal; and with those three rods (one 'real' and two false ones) he began to treat the patients in his practice by telling everyone that it was the authentic rod. The results of the book show that the percentage of success was identical, using the rod used.

With this simple experiment he demonstrated both that the rods were a fraud and the powerful influence of the attitude and motivation of the patient in the disease.

But how exactly does this motivation work? The placebo effect is perhaps one of the great paradoxes of medicine: essential in all pharmacological trials, its importance has been reduced to the category of "false medicine", partly due to the difficulty involved in its study, as is the case with the mental processes. Now, with new tools, such as functional magnetic resonance imaging (FMRI), the latest research on the placebo effect places it on a more measurable plane than pure imagination, even reaching the molecular level: certain neurotransmitters would be activated to physically heal the body of certain diseases, especially those related to stress.

Haygarth also paid no special attention to the effect itself and did not baptize it. The name placebo does not appear in the medical literature until 1832 and its origin is doubtful. There are two different versions.

One indicates that the origin comes from Psalm 116, verse 9 of the Latin version of the Bible (the vulgate) that says: "Placebo domino in regione vivorum", whose translation would be "I will flatter the Lord in the land of the living". This verse is recited as a responsorial psalm in the office of the deceased and in nineteenth-century England it was popularly called a placebo to the person who sneaked into a funeral without knowing the deceased to eat and drink for free.

Another explanation, perhaps more plausible, would be that the name is taken from medieval English, where placebo would be translated as "false praise" or "flattery". In the "Tale of the Clergyman", one of The Canterbury Tales, collected by Chaucer in the fourteenth century can be read: "Flatters are the devil's chaplains that continually sing placebo" (the flatterers are the chaplains of the devil who continually sing flattery [placebos]) and in fact Placebo is the name of a character who is deceived by his wife in another of the stories ("Tale of the merchant").

A red pill is more effective than a blue one, unless you're Italian

Regardless of the origin, we have been studying it for more than 200 years and it never ceases to amaze us. We know that an expensive placebo is more effective than a cheap placebo, that a red pill is more effective than a blue pill, except in Italy, probably because the blue jersey of the Italian team makes people feel identified with this color. A placebo injection is more effective than a pill and an operation where you sleep, open and close without doing anything is more effective than a pill or a placebo injection. That is why the evaluation of any medication is done in a double-blind study, comparing the study drug with a placebo, because otherwise the result would be that any substance would give a positive result.

The placebo effect is one that takes advantage of ineffective therapies such as homeopathy. Another myth associated with placebo, and often defended by pseudomedicine, is that if it were a placebo, it would not work in babies or animals. This is not true and there are numerous studies that prove it. Animals and babies also feel the attention or care we give them and that has a measurable effect on the healing of the disease.

You just have to do a simple experiment. When we are with a baby or with a child who has fallen or hurt himself and is crying in anger, it is enough to hug him and give him love so that all the pain will be relieved. The "healthy cure, frog's ass" that our mothers gave us is a tangible evidence of the use of the placebo effect in children.

And we must not forget that the placebo effect has two tenebrous brothers. The nocebo effect is when you think something innocuous is going to hurt you and really does it to you. This effect is behind many psychosomatic pathologies. And there's also the lessebo effect, which happens when you participate in a clinical trial, you think you're dealing with the placebo because you've been included in the control group when you're actually being treated with the experimental drug. Under these conditions, an effective drug may no longer have an effect.

More than a psychological effect

What we are seeing in recent years is that the placebo effect is not just a psychological effect or something that depends solely on our attitude or our perception of pain. Now we have better tools to measure the placebo and we are seeing that this effect reaches the molecular level.

For example, a study published a few years ago said that placebo treatment of Parkinson's patients increased endogenous dopamine levels. At the last global congress on placebo, organized in Leiden recently, the latest studies were presented using FMRI (functional magnetic resonance imaging) that show that areas of the brain are activated after taking a pill of sugar if a doctor It tells you that what you are taking is a medication.

In the same way it has been seen that the placebo effect is dependent on a family of neurotransmitters called catecholamines – to which adrenaline, norepinephrine and dopamine belong – implicated among other factors in the stress response. The recent work of scientists such as Kathryn T. Hall, molecular biologist, and Ted J. Kaptchuk, head of the Placebo Studies Program at Harvard Medical School, who have discovered that certain mutations in an enzyme called catecholmethyltransferase (COMT) – that alter the levels of these neurotransmitters – can predict whether a patient will have a greater or lesser placebo effect, demonstrating that this effect may have a genetic basis.

These advances open the door to new questions: if it is proven that our response to the placebo effect depends on our genetics, should medical attention adapt to the patient's DNA, administering drugs to those with a weaker response to placebo, but attentions capable of suggesting those with lower COMT levels, and therefore more sensitive to the effect? Would it be useful for drug trials not to include in the trials those people with the greatest response to placebo to better isolate the effect of the drug being tested?

It is not possible to directly control COMT levels in the brain of a living person, but perhaps it is possible to influence the rs4680 genome that governs the production of the enzyme. If the placebo effect is the result of a series of neurochemical events related to this enzyme and the neurotransmitters it regulates, what would prevent pharmaceutical companies from creating a drug that controls that process in the desired direction?

We have much to know about the mind-body relationship and its effect on the disease, although we have better tools to study it. Science is eating the land to the spirit, also in medicine.

José Miguel Mulet holds a Ph.D. in Biochemistry and Molecular Biology and is a tenured professor in the Department of Biotechnology at the University of Valencia. As a disseminator, he has published Medicine without cheating or Transgenics without fear. His latest book is What is healthy eating? (Planet, 2018).



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