In 2004, María Jesús, 64, felt the first discomfort. Despite being overweight, she had always been very active, until her right knee began to give her problems. He would get up in the morning and feel a strange stiffness that gave way to pain when he put his foot on the ground. Little by little, she was unable to walk. According to the doctor, he suffered from osteoarthritis and had to undergo a quick and easy surgical procedure known as arthroscopy . This joint flushing intervention produces lasting relief in 80% of patients, and it also did its work with María Jesús, my grandmother. But in reality there is no evidence that it cures or stops osteoarthritis . In 2002, a group of American scientists, intrigued by this circumstance, decided to investigate the true effectiveness of the operation, with surprising conclusions.
And it is that when compared with a sticky intervention, designed to convince patients, arthroscopy does not achieve better results. Despite this, “it is the most common of orthopedic surgeries, and the knee, the joint where it is performed most frequently,” recalled the North American experts in the New England Journal of Medicine . So why do most of those who go under the knife respond so positively?
This has been asked for more than fifteen years by Ted Kaptchuk, director of the Placebo Studies Program at Harvard Medical School. Kaptchuk practiced acupuncture for years, although some miraculous recoveries convinced him that something more had to be at stake. It is known that certain people are capable of improving at the slightest hint of a treatment . “I always thought that the suggestion, the ritual, the beliefs and all those ideas that make scientists nervous were important components,” he explains.
When Kaptchuk arrived at Harvard in the late 1990s, most of his colleagues viewed placebos as merely harmless sugar pills, the benchmark against which the effectiveness of a real treatment was compared. However, he sensed its healing potential . “If people felt better, it seemed to me that they could be used as a therapeutic adjunct,” he says. The problem was, unless you found out empirically how this process works, your idea would be hard to come by.
The importance of the human factor
The American expert began to investigate seriously, and the first thing he discovered was that not all placebos act the same . A saline injection or a dummy acupuncture needle stick is more effective than a pill, so the method of administration influences the result. Furthermore, it was evident that between the practice of conventional and alternative physicians there used to be a difference in terms of treatment and time devoted to patients .
With the collaboration of gastroenterologists from Harvard Medical School, Kaptchuk designed an experiment in 2008 to quantify the importance of this human factor. So he selected 262 people with irritable bowel syndrome, a chronic gastrointestinal disorder linked to stress . It was a perfect target: in addition to pain, ailments such as depression and anxiety respond quite well to placebos, perhaps because of their more direct relationship with the mind.
The volunteers were separated into three groups. The first received no treatment, the second underwent acupuncture sessions with needles that did not pierce the skin, and the third received a similar pseudo-therapy, although dispensed by doctors who expressly showed interest in his symptoms and discomfort .
Result: while the patients in the second group did not notice anything, those in the third did experience significant improvements. These results supported what is now known as the effect of care , and would explain why patients with osteoarthritis perceive benefits after undergoing arthroscopy. Despite everything, little or nothing has been done to include these findings in daily clinical practice, and many doctors accept without question the importance of the placebo effect when it comes to alternative therapies.
Antidepressants in question
Another example of this rejection is the discussions that are generated around the work of Irving Kirsch, deputy director of the Placebo Studies Program. The research carried out by Kirsch indicates “without a shadow of a doubt”, as he explains to MUY, that antidepressants are no more effective than a pill without active ingredients , data that have been known since 1998.
Despite this, its conclusions are still controversial, and have not been reflected in the use – and abuse – of these drugs, “something worrisome if we take into account their possible side effects,” says the expert. And he adds: “Current medicine reacts to this evidence trying to enhance the action of drugs when it should seek to increase that of placebos.”
Some critics claim that it is an unethical approach, because it involves depriving the patient of real therapy. But this opinion seems far from reality if we take into account that most doctors recognize the usefulness of placebos: the data suggest that their use is widespread .
“Actually, most of the products that are sold in pharmacies, the so-called over-the-counter drugs, have no pharmacological effect. The perception of their usefulness is due to the fact that they are often administered when the disease begins to remit. For example, a common cold does not usually last more than a week, when we rarely take the drug before the third day. In this way, its natural course solves the problem in a couple of days, but we believe that the pills have the credit ”, says Fabrizio Benedetti, who works at the Faculty of Medicine of the University of Turin. Since the mid-90s, Benedetti has been studying placebos as a tool, according to him, to understand the functioning of the brain .
Its scientific interest is unprecedented. In the late 1970s, Jon D. Levine, Newton C. Gordon, and Howard L. Fields of the University of California, San Francisco, noted that without anesthetic intervention, some people experienced tooth extraction as an experience. traumatic , while others only manifested a certain discomfort. The discovery of endorphins in 1974 had shown that, subject to certain stimuli, the body is capable of manufacturing powerful painkillers. Could these neurotransmitters be involved in the placebo effect?
To test their hypothesis, the researchers first established who felt the least pain after receiving a saline injection. If endorphins were responsible, a blockade of the receptors used by them in the central nervous system would deactivate them. So it was. Because these substances are natural opiates, they could use naloxone, a drug used to counteract morphine or heroin intoxications. With a single dose, even the most placebo-sensitive patients stopped feeling its benefits .
Published in The Lancet, it was only the first study to demonstrate such real physiological effects. Technologies such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have made it possible to detail what happens in the brain in real time when the response is activated . “It involves a large number of molecules; many times, the same ones that are activated with real drugs ”, says Benedetti. Research with Parkinson’s patients, for example, showed that an injection of saline solution promotes the synthesis of dopamine, the neurotransmitter affected by this ailment. In other words, the same thing that drugs try.
The risk of prescribing them
Such revelations highlight the urgent need to study this phenomenon , since it can interfere with drugs that depend on the activation of the same brain circuits. In addition, most specialists agree that the widespread use of placebos by family doctors, without knowing all the details of their operation, carries certain risks. For example, most doctors admit to having prescribed antibiotics knowing that the patient suffered some type of viral infection, against which they have no effect. And the dangers of taking these drugs unnecessarily are well known.
The risks are so real that, in some cases, they lead to irreversible damage and even death. In 2011, Kaptchuk led a study on asthma. As was the norm, the placebo group noticed improvement, so the researchers thought that the dummy inhaler was capable of restoring lung function. The surprise arose when they found that it was not like that: only the real drug fought the symptoms .
The discrepancy between the objective results and the subjective notions of the patients can therefore be fatal. As the former military doctor Harriet A. Hall, a well-known critic of alternative medicines, explained in an interview for the American magazine The Atlantic, “if something ineffective makes those affected feel better, it could dangerously delay the administration of treatment.” For this expert, most of the studies on the beneficial consequences of the placebo actually show that such a thing does not exist; the observed result is exactly the same as if the patient is not treated .
It refers, above all, to various articles published by Danish scientists over the last decade. Asbjørn Hróbjartsson, a researcher at the Cochrane Nordic Center in Copenhagen (Denmark), and one of the authors of the aforementioned studies, qualifies Hall’s conclusions: “Although they usually have a modest effect, the reactions are very varied . Furthermore, we do not consider the doctor-patient relationship or other approaches ”.
There is no single effect
For Hróbjartsson, his research does not deny the existence of the placebo effect; they simply show that more rigorous methods are necessary to understand it: “We are talking about something very complex,” he sums up. Different stimuli give rise to such different reactions that some scientists advocate no longer using the same term to refer to all of them .
Along the same lines, both Kaptchuk and Benedetti defend that there is not one, but many placebo effects , conditioned by a multitude of factors. Expectations are, of course, important: according to an experiment carried out by the Italian scholar, something as prescribed as diazepam – better known by its trade name, Valium – is only effective if the patient knows they are taking it. Anyway, Benedetti clarifies that the predisposition depends on the previous learning and the changes that have operated in the consumer’s brain.
For example, after a patient experiences pain relief from morphine, the neurological pathways activated by a placebo are different from those in someone who has had a similar experience with a different compound, such as ibuprofen. This is how Benedetti explains it: “When a patient receives morphine for three or four days, his brain learns to associate the treatment with a reduction in pain. If a paste pill is administered on the fifth day, the vast majority will continue to state that they feel less pain, ”explains the expert. And he adds: “However, if the pseudo-drug is used the first day, only a small percentage of patients will respond positively.” And the same happens with everyday pain relievers: “We learn to associate a small white pill – aspirin – with a decrease in headache .”
Predrag Petrovic, from the Karolinska Institute, in Stockholm (Sweden), has developed a theory about the origins of this phenomenon. It defends that it is nothing more than a consequence of information processing . For Petrovic, who published in 2002 the first description of the neural mechanisms involved in the analgesic action of placebos, “it is nothing more than a strategy of the brain to minimize the differences between what it thinks is going to happen and what actually happens. ”. According to their studies, the orbitofrontal cortex and the anterior cingulate cortex are responsible for altering anticipation and modulating the reaction in the event of a mismatch. “The level of connectivity between these two regions determines a person’s ability to respond to placebos,” he conjectures in a paper published in 2010.
Alzheimer’s sufferers, immune
In the absence of conclusive data to confirm it, no one doubts that expectations play a key role. A good example is Alzheimer’s patients, immune to false treatments. In addition, they must take very high doses of painkillers to combat pain. Why? In 2006, Benedetti showed that it is because the areas of the brain involved in forecasting the future have problems connecting with other areas , and do not correctly receive signals from endogenous opiates.
It is clear that if the difficulties of the nervous system to combat physical suffering are added to the lack of hope about the success of the treatment, even the most powerful drugs lose their effectiveness.
These findings sparked a battery of experiments to unravel the complex neurobiological mechanisms involved in responses to placebos. However, “it is not clear how we can use that knowledge to develop practical tools in a clinical setting,” Andrew Geers, of the University of Toledo, Ohio, and Franklin Miller of the National Institutes of Health noted in a recent article. Americans. Both criticized the fact that so much effort has been invested to understand brain springs without delving into the psychological processes that condition them. “A knowledge that would allow the design of intervention techniques without deception”, Geers and Miller assured.
Because, indeed, the vast majority of the studies carried out on this subject were carried out without the patients knowing that they were receiving a treatment of stickiness, actions that raise serious ethical doubts. What nobody expected was that the charade, in addition to damaging the doctor-patient relationship, was useless , as a study led by Kaptchuk in 2010. Even when patients with irritable bowel syndrome learned that their medicine did not It was more than a sugar pill, the results were comparable to those recorded in clinical trials conducted with real drugs.
Trust from doctors helps
Both Kaptchuk and Benedetti argue that healthcare professionals who wish to use these discoveries should focus on what is known as a therapeutic ritual. “Your attitudes, words and actions are very important. If the doctor is able to improve the patient’s expectations about the therapy to receive, there will be a reduction in anxiety and, without a doubt, a more satisfactory response ”.
According to Kaptchuk, “even unconscious signals are key to success.” A statement corroborated by Karin Jensen, from the Placebo Studies Program, who two years ago scanned the brains of several doctors while they were consulting . This experiment made it possible to conclude that the doctor’s beliefs about the treatment, even if they are not expressly mentioned, condition the patient’s predisposition about the good that he is going to do.
For now, manipulating all of these factors to achieve objective results is still a mirage. However, the fact that placebos work even when the patient knows they are taking them opens the door to a midway approach: hybrid procedure design . “They will not cure viral ailments or tumors, but used in conjunction with other actions they are capable of, for example, alleviating the symptoms of chemotherapy or making flu bearable,” says Kaptchuk. An alliance capable of eliminating certain side effects and that, finally indicates Benedetti, can also enhance the effect of drugs, which would allow reducing doses.
