What is the psychological mechanism of the placebo effect. Placebo effect: what is it? Placebo in psychology

Cardiologist Yaroslav Ashikhmin talks about drugs without proven efficacy, their mechanisms of action, and clinical studies of the effect of placebo on the body.

A placebo is a substance with no apparent medicinal properties that can be used as a drug or mask the drug. The phenomenon of improvement due to the use of such a drug is called the placebo effect. This effect can be traced in a number of mental illnesses, pain syndrome, bronchial asthma, Parkinson's disease, irritable bowel syndrome, coronary heart disease and arterial hypertension.

The effect of using a placebo is not as reliable as the effect of using real drugs. Placebo due to the placebo effect can lead to some subjective improvement in the condition, but it rarely cures the disease. A person may feel an improvement in the condition, which is not due to the fact that the disease has “receded”. For example, a patient may feel better on the background of the use of homeopathy, which acts precisely due to the placebo effect.

The history of the use of placebo in clinical medicine began a long time ago. For example, the famous doctor Matvey Mudrov, who lived in the 18th-19th centuries, used simple, gold and silver powders that eased the pain of patients. Only after the doctor's death did it become clear that ground chalk served as the main component of these powders.

Placebo today

Firstly, placebo is used to relieve the patient's pain when effective drugs are not available.

Secondly, it is prescribed for the possible improvement of a condition when there is no certainty about the effectiveness of an existing drug.

Thirdly, it is being used unknowingly- for example, when a doctor prescribes a drug, being sure of its effectiveness, but the drug does not work. The third situation is the most dangerous, because drugs that seem safe at first glance may have hidden side effects that are observed after a long time.

A large number of different neurophysiological mechanisms are involved in the implementation of the placebo effect: the endocannabinoid system, dopaminergic, endorphin systems. When using a placebo, certain areas of the brain are activated: the prefrontal cortex, the anterior cingulate gyrus (previously referred to as the "pleasure center"), the nucleus presenting. A combination of mental and neurological mechanisms is involved. In this case, suggestion plays an important role.

placebo experiment

For example, in one study, patients with migraine were divided into two groups. One group was given a placebo, but it was said to be a powerful migraine drug, Rizatriptan.

The other group was given Rizatriptan, a real headache remedy, but was told it was a placebo. There was no difference in efficiency.

That is, the doctor's words that the patient is receiving a strong medicine acted as effectively as the Rizatriptan medicine itself, when they did not know about it.

But when patients were given "Rizatriptan" and told that it was "Rizatriptan", the effectiveness of the drug in terms of relieving headaches increased by 50%.

Interestingly, the placebo appears to be more effective when administered via droppers. If the administration of the drug is sensitive to patients, then its effect is higher.

The analgesic effect of a placebo in the same migraine is higher by 7% if the doctor gives an injection, and does not offer the drug in tablets.

And the price of the drug also plays a role: if you tell the patient that the drug, which is actually a placebo, is more expensive, then it turns out to be more effective.

Persuasion plays a very important role. In addition, even the presence of the psyche is not necessary for the placebo effect to work - there are a number of studies that have shown the effectiveness of placebos in animals.

A placebo can be comparable in efficacy to a drug in diseases in which a decrease in the quality of life is primarily due to mental disorders and pain. But we must remember that such an improvement in physical condition is not always translated into an improvement in physiological parameters.

For example, the placebo effect appeared during World War II. When the medicines ran out, the shell-shocked soldiers were injected with saline under the guise of morphine, and this reduced the pain. But not always the mechanism of action of a conditioned saline solution has a purely psychological basis. For example, in a number of studies, scientists, in order to relieve pain, also brought to the nerve fibers not analgesics, but saline. It turned out that saline can somehow act on nerve fibers and also relieve pain.

If the main purpose of the drug is to relieve pain, a placebo may work and achieve the desired effect. But this effect will be less long-lasting than the real drug. A placebo can be used to relieve pain, but a placebo is highly unlikely to cure diseases.

Homeopathy, which works only due to the placebo effect, helps to improve the psychological picture of the perception of the disease, but at the same time it does not, under any circumstances, eliminate the disease itself.

The use of homeopathy (by the way, read the text on Zozhnik - ““) is a gross violation of bioethics in situations where there is a real medicine or when it is known for sure that the placebo is ineffective.

In addition, it is forbidden to use homeopathy in the treatment of bacterial infections, heart disease, rheumatological diseases, for which drugs are already known that work accurately. In other words, if there are drugs with proven effectiveness, the use of homeopathy is criminal. But if there are no drugs with proven efficacy, as in the treatment of SARS, the use of a placebo is acceptable.

In a recent study of the work of British medical practitioners, it was noted that an implicit placebo, that is, a placebo that is prescribed when doctors doubt the effectiveness of the drug, was prescribed by about 97% of doctors, and pure placebo, that is, the same conditional saline solution, was prescribed by 12% of British doctors . Among Russian doctors, pure placebo is even more popular. This is due to the fact that people in Russia often believe that observation in the clinic must necessarily be associated with parenteral administration of drugs. Therefore, in the Russian tradition, many patients are given droppers with saline, that is, with a pure placebo. When evaluating the ethics of this event, one must take into account the cultural factor, because many of them really “help” a lot.

Identified in the middle of the twentieth century by physicians, but in fact, of a purely psychological nature, the Placebo Effect still proves what possibilities human faith and self-hypnosis allow to discover.

Religion is not the opiate of the people. Religion is a placebo for the people.
Dr. House

Excursion into history

The concept of the "Placebo Effect" appeared in the medical literature in 1955, when the American physician Henry Beecher discovered that some patients begin to feel better by taking drugs that have no medicinal properties at all.

Even during the Second World War, while working as an anesthetist in a military hospital, he noticed that sometimes the effect of saline and a real drug almost coincide. After the war, Henry Beecher began to seriously study this phenomenon, collecting in 1955 the conclusions of his work in the publication "The Powerful Placebo".

The key to this phenomenon is not only the faith of the patient and the attending physician in the power of the drug, but also the faith of the entire staff. In the placebo study, many experiments were conducted, one of which is especially recorded in the history of psychiatry.

In 1953, in one of the psychiatric hospitals near Washington, where residents of Puerto Rico and the Virgin Islands were treated, a group of patients with strong manifestations of aggression was urgently hospitalized. The psychiatrist E. Mendel supervised this group of patients.

The doctor decided to test the new tranquilizer reserpine using a double-blind experiment. Some of the patients gave out a real drug, and some of the usual sweet pills. The doctors themselves did not keep track of which group received which pills. And all the patients were sure that they were taking a tranquilizer.

A few months later, according to the calm behavior of the patients, it became clear that the new remedy was quite productive. A well-known psychiatrist was impressed by the action of reserpine, but it soon became clear that many patients received a placebo.

Soon Mendel realized that the condition of the patients returned to normal only because of his belief in improving the behavior of patients. He began to calmly relate to his wards, and they answered him the same.

Secrets of the placebo effect

One of the secrets of the unique phenomenon is related to the ability of a person, or rather a patient, to be suggestible and unconsciously trust the attending physician and psychologist.

Through the placebo effect, doctors determine the quality of the drug. If one patient took a placebo and the other a real drug, but the result was about the same, then the drug does not have a sufficient positive effect.

Along with the placebo, another opposite phenomenon is also known in modern medicine - the nocebo effect. It can manifest itself as nausea, allergies, dizziness and increased heart rate in patients taking the "fake medicine". According to strange statistics, the nocebo effect is caused by the nervous staff of the hospital, and by prescribing a medicine to calm the sick, the doctor thereby calms himself.

This phenomenon is called " placebo rebound».

Homeomatic medicines that are popular today are also based on the placebo effect. When talking and simulating the treatment process in this case, all human reserves are connected.

The placebo effect has become a new vector not only in medicine and psychiatry, but also in the development of pharmaceutical products. For example, many drug manufacturers are trying to produce bright large pills, the effect of which is much better than small "nondescript" pills. And patients calmly use drugs of familiar companies, whose names they hear on television, rather than products with the same content, but unknown manufacturers.

Autosuggestion activates the release of endorphin, which sometimes replaces the effect of the drug, and includes a "mobilization function", which implies strengthening the immune system. The strength of the placebo effect depends on the degree of exposure of the person to the influence and the ability to produce the necessary chemicals.

The effect of the placebo effect on different categories of people

For example:

1. In children, the placebo phenomenon is much more pronounced than in adults;
2. The placebo effect is stronger on the emotional and addicted

In some sources, the placebo effect is defined as a drug prescribed to satisfy the desire of the patient rather than for a curative effect. The literature describes cases when a doctor prescribed to patients a particular drug that was not endowed with an effective property, but at the same time the patients were inspired that the drug was very effective.

As a result of such treatment, in fact, there was an improvement in the well-being of patients. There have been cases when patients also showed side effects attributed to the medications taken.

Although in fact there were no components characterized by a similar effect in the drug. This is explained by the fact that under the influence of self-hypnosis in the body of a person taking a placebo, self-healing processes are launched.

The placebo effect is such an effect on the body when a medically ineffective treatment gives positive results based on the body's ability to heal itself. A subjective or real change in the state of health depends on the patient's psychological confidence in the effectiveness of treatment.

As a rule, drugs with a neutral effect are used, and the positive effect is associated either with a natural improvement in the patient's well-being during recovery, or with self-hypnosis in the usefulness of this treatment. The opposite placebo reaction is also known - nocebo, translated from Latin meaning "I will harm."

The figure shows what it is - the placebo effect.

In a situation where the patient is convinced of the ineffectiveness of the treatment, with a high degree of probability, the patient's condition may worsen. Often in such situations, negative symptoms are observed that could not be caused by the drug being taken. Patients associate the occurrence of these symptoms with the action of the drug.

Classification

The placebo effect is a property that has been studied for quite some time, but a clear definition has not yet been obtained. Most often, procedures or medicines are implied, the use of which, from a medical point of view, has a neutral effect. Based on this, the concept of placebo can include not only drugs that are common everywhere.

This effect extends to a wider range of funds.

• Medical preparations. Pharmacological companies produce a considerable number of drugs, the effectiveness of which remains in doubt. Of course, such drugs are not intended for the treatment of serious diseases. But for the treatment of minor diseases, drugs may well be prescribed, the effectiveness of which is based on the patient's confidence in the beneficial effects of the drug on the state of health.

• Imaginary surgical interventions. In the history of medicine, there are cases when surgical interventions were only suggested to patients, but were not actually carried out. An important role was played by reliable preoperative preparation of the patient, appropriate manipulations after the “performed” operation. When a reliable performance was played out in front of the patient, convincing of the reality of the surgical intervention, the patient's body reacted accordingly.
• Acupuncture. This healing method is of Eastern origin. The belief that by pricking needles into certain points on the body, you can get rid of ailments, and now helps in the treatment of many patients.
• Homeopathy. The effectiveness of drugs that are commonly called homeopathic causes a lot of controversy, but their use is quite widespread.

Who does placebo work on?

The placebo effect is a remedy that can manifest differently for different people. The practice of using drugs shows that in children, treatment with pacifiers is more effective than in many adults. Positive results are also given by therapy with similar drugs in patients with mental disorders.

This form of treatment is most effective for people who are more suggestible than for those who question and recheck any remedy. For the latter, the result is likely to be zero. Susceptible people, taking a drug - a pacifier, not only experience the sensations corresponding to the treatment, but they may also notice manifestations of side effects that the drug being taken cannot produce.

Practical use

• These days, placebos are quite often given to patients who tend to look for manifestations of all sorts of diseases. Since in such cases the disease exists only in the head of the patient, it is more expedient to treat it with methods based on suggestion in order to avoid excessive drug effects on the body.
• Placebo agents are also widely used to control the effects of new drugs.
• Treatment of alcohol and drug addiction is also not complete without placebo drugs. In the process of treatment, patients are instilled with the desire to get rid of the disease.

• Placebo is also used effectively in psychiatry. Suggestion-based treatment makes it easy to correct various mental disorders, whether they are depressive states, sleep disorders, or deviations from the norm in the sexual sphere.
• Placebo drugs are also used in sports. The athlete's belief that the mixture being taken is doping contributes to increased performance.
• Preparations - pacifiers help to get rid of ailments of a psychosomatic nature, since it is easier to remove the influence of the psyche on the human body with the help of suggestion.

Psychological features

The placebo effect is based on suggestion, so this method is most widely used by psychologists and psychiatrists. The scope of use is not limited to the treatment of any abnormalities in the mental state. This property is included in the educational and upbringing processes in order to achieve a greater effect in the development and stabilization of patients of any age group.

A fundamentally important component of the healing process using the placebo effect is the correct preparation for recovery.

Feeling the positive impact of the applied treatment on the patient's condition becomes a prerequisite for real improvement. The patient's conviction that the medicine used has specific properties contributes to the mobilization of the body's own resources to defeat the disease.

Mechanism of effect in medicine

From a medical point of view, the mechanics of the manifestation of the placebo effect is that under the influence of conscious and unconscious expectations, the human body triggers certain mechanisms of vital activity. The body begins to produce certain hormones, enzymes or other substances that affect physiological processes.

The external manifestation of these changes may be the removal of pain, reduction of fatigue, anxiety and other negative symptoms, which were aimed at combating the use of the drug.

Practical use

The effect of self-hypnosis can be accompanied by both the use of drugs and other types of therapy and even surgery. Therapy can only be reduced to suggestion. This form of medical influence on the body is called the placebo method.

The decisive factor is the preparation of the soil for treatment. The patient must believe in the effectiveness of the manipulations. Only in this case, his body will give an appropriate response to treatment.

Drugs considered placebo

Because placebo treatments rely heavily on patient deceit or self-deception, the use of placebos is controversial. Nevertheless, modern pharmacological companies continue to develop and bring to the market new drugs of this kind.

Of the entire list of medicines used by doctors today, a third of them are drugs - placebo. As a rule, such drugs are quite expensive, but they are trusted by both doctors and patients.

Some of the more common placebo drugs include:

Surgical intervention

Scientists have conducted studies on the presence of the placebo effect during surgical interventions. As a result of the experiments, it was found that a properly arranged, although not actually performed, surgical operation produces an effect similar to a real surgical intervention.

The first imaginary operations were carried out in the middle of the last century in the USA by surgeon Leonard Cobb. He assured patients suffering from diseases of the cardiovascular system that they had undergone heart surgery. But in reality, the patients made an incision on the chest in the region of the heart, followed by suturing.

The vast majority of patients showed improvement. At the end of the last century, another surgeon conducted an experiment with imaginary surgical interventions on the meniscus. Some of the patients were actually operated on, while others were given a convincing performance of the operation. After that, all of them showed an improvement in their condition.

Acupuncture and homeopathy

Acupuncture has a thousand-year history of use. The basis of this method is not just a mechanical effect on certain points of the human body in order to provoke certain processes. Without the appropriate psychological preparation of the patient, that is, without the suggestion component, the positive effect of acupuncture is significantly reduced.

In this regard, acupuncture treatment can also be attributed to placebo methods.

Widespread homeopathy also has a component of psychological impact on the subconscious. The conviction that the drug favors the improvement of the condition allows using neutral syrups to use the body's own reserves for self-healing.

What enhances the placebo effect

Numerous studies of the patterns of manifestation of the effect made it possible to find out the factors that influence the enhancement of the beneficial effects of placebo on the body. With a similar composition and properties of the components, tablets of various sizes, shapes, colors are perceived differently.

So a large therapeutic effect is characterized by tablets of a larger shape. Bitter potions are more effective than sweet ones. Medicines taken 2 tablets at a time also have a more pronounced effect.

A large role in the formation of confidence in the effectiveness of the tool is played by its appearance. The placebo effect is enhanced by bright packaging, various engravings on the tablets. For the treatment of different diseases, it is more effective to use a medicine of a different color. So, to get rid of the symptoms of anxiety, green pills contribute, and yellow pills are effective in the treatment of depressive conditions.

The intensity of the manifestation of the placebo effect for representatives of different nationalities is influenced by different factors. In the course of testing, it was found that Russians and Americans prefer drugs in the form of injections or droppers, while Europeans trust capsules more.

The placebo effect is manifested to varying degrees in the treatment of various diseases. The greatest effectiveness of the use of drugs - pacifiers was noted in the field of treatment of depressive conditions.

The effect is also enhanced by the high cost of the drug and its inaccessibility. The reputation of the prescribing physician also affects the degree of trust in the drug, and therefore the effectiveness of the treatment.

The manifestation of the effect is not affected by the awareness of patients that the drug is a dummy. In the course of the studies, the same results were obtained in those patients who knew about the details of the experiment, and in those who were not privy to the details. Moreover, sometimes the positive dynamics was stronger in the informed group than in the uninformed patients.

Currently, the placebo effect poses more questions than answers for scientists. Combinations of various factors can provoke such manifestations that are difficult to reproduce repeatedly. The mechanisms of manifestation of body reactions to drugs and medical effects in this category have yet to be studied.

Useful videos about the placebo effect and its mechanism of action

What is the placebo effect:

How the placebo effect works:

Placebo (lat. placere - to like, to be appreciated) means a drug that obviously does not have any healing properties. In the 18th century, the word entered the medical lexicon and began to mean "fake medicine."
Here is how the Big Encyclopedic Dictionary defines this term: “A dosage form containing neutral substances. They are used to study the role of suggestion in the therapeutic effect of any medicinal substance, as a control in the study of the effectiveness of new drugs.
A more detailed definition is given by the Encyclopedic Dictionary of Medical Terms: “A pharmacologically indifferent substance that imitates a certain drug in appearance and taste. It is used in the study of the pharmacological effect of medicinal substances, as well as in therapeutic practice. A placebo is defined as "an inert substance that acts according to the expectations of the patient and is not able to act directly on the conditions for which it is prescribed to change."
In medical practice, there are two types of placebos. In some cases, indifferent substances are used to study the placebo effect, in others, special mixtures are used that correspond to the compositions of the dosage forms of the studied drugs. In this case, a placebo is used for a differentiated assessment of the therapeutic effect of the active substance contained in the pharmacological preparation. It should be noted that absolutely indifferent substances for the body do not exist. One can speak only of relative or absolute indifference in relation to the specific action of the studied object of research.
The phenomenon in which the expected action of a substance determines the body's response to it is called placebo effect. This reaction is manifested by a change in the physiological and psychological state of a person after taking a harmless drug, prescribed under the guise of an effective drug, compared with a control group receiving no drugs. The existence of a placebo effect may demonstrate the psychotherapeutic effect of the mere fact of taking the drug. It is not associated with the specific effects that a placebo substance may cause.
A positive placebo effect is a positive change, which is expressed in the form of improved well-being, relief of anxiety and anxiety; temporary normalization of sleep, indicators of the functioning of the cardiovascular and respiratory systems; reduce the severity of symptoms of cough, runny nose; reducing the frequency of attacks of bronchial asthma, angina pectoris, headache; increase in the volume of movement with sciatica; improvement in allergic rhinitis, peptic ulcer; weight loss; changes in the emotional sphere (reducing the severity of depression, improving mood); relief of pain of various origins, swelling with inflammation of the joints. Therefore, we can talk about a subjective improvement in well-being and an objective manifestation in the form of a weakening of the symptoms of the disease.
The term "placebo effect" was coined in 1955 by the American physician Henry Beecher, who found that about a third of patients recovered from empty pills containing no active ingredients.
There are very few detailed works devoted to placebo in the Russian-language literature. The monograph by I.P. Lapin, written on the basis of the author's many years of experience in studies of the placebo effect in healthy individuals and patients. He summarized and systematized a significant amount of information about placebo, placebo effects in various diseases, placebo control and placebo therapy. A lot of information about the placebo effect can be gleaned from the book of Dylan Evans, a researcher from the University of Bath (UK).
The question of whether there is a placebo effect was the subject of a systematic review by the Cochrane Library.
placebo effect objects. Specific manifestations of the placebo effect depend on the social and personal characteristics of a person, his condition and expectations. Myths include the fact that placebo only works on patients with hysterical accentuation of character. According to statistics, placebo affects all people, only with different strengths. It has been noted that there are more placebo-reacters among extroverts (i.e. persons whose feelings are directed outward). Such patients are anxious, dependent, emotionally labile, have a high level of agreement, and are ready to cooperate with doctors. At the same time, placebo non-responders are more common among introverts (people who are directed inward), incredulous and suspicious. The greatest reaction to placebo is given by neurotics, as well as persons with low self-esteem, insecure, inclined to believe in miracles. Placebo works best in patients suffering from mild psychosomatic disorders, such as insomnia or mild depression.
placebo properties. In the minds of many people there are several stereotypes about what medicines should be. First, they must be bitter. Secondly, the tablets must be either very large or very small. Large ones are associated in the patient's mind with a large dose of the drug, and small ones with high efficiency. Thirdly, a strong drug must necessarily have side effects, such as nausea, dizziness, headache, fatigue. If positive expectations create the prerequisites for recovery, then negative ones can affect the healing process, slowing it down. Negative placebo effects are called nocebo. If the patient knows what side effects the drug has, then in 77% of cases they occur when he takes a placebo. Belief in one or another effect can cause the appearance of side effects. When comparing placebo and fluoxetine in women, the nocebo effect was slightly more pronounced than in men. It has been proven that the nocebo effect is not only of a psychological nature, but placebo-induced hyperalgesia is caused by cholecystokinin and is eliminated by its antagonist, proglumide.
Numerous studies have shown that the social environment in which drugs are used is directly responsible for placebo effects. Thus, clinical observations of patients showed that:
tension among staff causes nocebo effects;
prescribing anti-anxiety drugs to patients significantly reduces anxiety among medical staff (this phenomenon has been called “placebo rebound”);
skepticism of doctors and staff greatly reduces the effect of drug therapy;
a placebo effect was recorded in the control group of patients who underwent outpatient treatment, compared with those who took the same drugs, but were isolated in the hospital;
belief in the power of drugs by the doctor himself and nurses is considered the main factor in determining placebo effects.
Devices or carefully designed procedures were more effective than taking pills. It is believed that the most pronounced placebo effect occurs with the injection route of its administration.
Scientists have found that the placebo effect depends on the appearance and color of the pills. So, in the study of the analgesic effect of placebo tablets in 24 patients with rheumatoid arthritis, depending on the color, it was found that it decreased when they were taken in the following sequence: red, blue, green, yellow. At the same time, the color of the tablets did not affect the effectiveness of active drugs.
According to a cross-sectional study, in 48 patients with anxiety disorders, green diazepam pills were most effective, red least and yellow the least. On the contrary, for depression, yellow tablets were more preferable, less green and least red.
A double-blind crossover trial examined the effect of orange and blue pills in 120 patients before minor surgery. The patients thought they were being given a tranquilizer. Individuals who did not show a preference were excluded from the analysis. In the remaining group, 62% of men preferred orange pills and 61% of women preferred blue pills.
In a blind study, medical students were asked to take sedative or stimulant drugs in the form of blue or pink placebo pills. Those who received the blue pills felt less anxious (66%) as well as more sleepy (72%) than the students who took the pink pills (26%).
In a randomized crossover trial, 96 surgical patients received the hypnotic agent or placebo on the first night. On the second night they all took another drug of the same color. At the same time, patients who received blue capsules fell asleep faster than those who were prescribed orange (103 and 135 min, respectively; p<0,05). После приема голубых капсул больные спали дольше (379 и 346 мин соответственно; р<0,01).
An analysis of 12 publications showed that red, yellow and orange tablets are associated with a stimulating effect, while white and green tablets are accompanied by a tranquilizing effect. It has been established that red tablets or capsules are more effective in the treatment of children.
For the manifestation of the placebo effect, an important factor is the number of pills taken. Thus, after analyzing 71 controlled studies of the treatment of persons with peptic ulcer using endoscopy, the author concluded that placebo is effective in about a third of patients. Although none of the trials identified untreated patients, the number of indifferent tablets administered varied. The results of a meta-analysis conducted by other researchers showed that the treatment effect was statistically more significant among those who used 4, rather than 2 tablets.
When prescribing drugs, the authority of a specialist plays an important role: any medicine taken from the hands of a “deserved”, gray-haired famous doctor, professor, academician will be much more effective for many than the same remedy obtained in the district clinic. The price of the drug has a similar effect: if the drug is expensive, rare, difficult to obtain, then it will act more effectively on neurotics. Therefore, many people buy medicines from Western manufacturers, in bright packages, although you can buy a domestic analogue for an order of magnitude cheaper. A brand-name placebo has been found to have a more pronounced effect than a little-known drug.
The inclusion of additional ingredients in placebo that mimic the side effects of the study drug, but do not have a specific effect, had a more pronounced effect.
Factors that affect the placebo effect are presented in the table.
placebo effects. Serious study of placebo effects is believed to have begun in the United States during World War II. Front-line hospitals were very short of painkillers and drugs. Convinced once again that the injection of saline has an effect of almost the same severity as that of morphine, the anesthesiologist Henry Beecher, having returned to his homeland, with a group of colleagues from Harvard University began to study this phenomenon. In 1955, he summarized his observations in "The Powerful Placebo" in which he argued that the placebo can "cause significant physiological changes", including "objective effects in target organs that may be more pronounced than due to strong pharmacological effects." Based on the results of 15 studies, which included 1082 participants, he found that when taking a placebo, 35% of patients experienced significant relief when instead of conventional drugs for a wide variety of diseases (cough, postoperative and headache, irritability, etc.) received a placebo. In the future, it was proved that the effectiveness of placebo in the treatment of depression is 59% of that of psychotropic drugs.
A placebo can act not only as an indifferent, pharmacologically inert substance, but also as a medical procedure and even verbal influence. Anything that mobilizes the patient's expectations and beliefs about health can act as a placebo.
Often the placebo effect is found in surgical treatment, since it is more pronounced for patients. So, in one of the studies conducted in Denmark, 15 people during the experiment were operated on in connection with a disease of the inner ear (Ménière's disease), the other 15 underwent placebo surgery. After three years in each group, 10 people (the same number!) Almost completely got rid of the symptoms of the disease.
In another described case, patients undergoing dental surgery were prescribed ultrasound therapy. As a result, a decrease in the severity of pain and edema was noted not only among those exposed to ultrasound, but also among those who underwent an imitation of the procedure with the device turned off.
Interesting results were obtained in another study. A group of people with Parkinson's disease underwent surgery to transplant into the brain of special nerve cells - the so-called dopamine neurons, 20 others were told that they had undergone the same operation, when in fact they were not subjected to any surgical interventions. At the same time, a double-blind control was carried out, that is, neither the patients nor the medical staff knew who was actually implanted with new cells. A year later, in both groups of patients, there were both those who believed that after the operation they began to feel better, and those in whom the doctors found clear objective signs of improvement in their condition.
The placebo effect has also been proven with acupuncture in the case when doctors performed acupuncture using points that are not biologically active. At the same time, a positive effect of the treatment was observed in 35-50% of patients, and the effect on true biological points was effective in 55-85% of cases.
In a crossover randomized study of 44 patients with chronic cervical osteoarthritis, the treatment methods used (acupuncture, sham acupuncture and diazepam) were found to be equivalent. The most pronounced result was obtained after the use of placebo.
Undoubtedly, the placebo effect is present in the prescription of homeopathic remedies, as well as in other types of treatment. Some researchers, after conducting a series of laboratory tests, found no evidence that homeopathy is somehow more effective than placebo. The authors believe that some people feel better after taking homeopathic remedies, however, they attribute this effect to the psychological factor, the experience of therapy in general, the time and attention that the homeopath pays to the person. It should be noted that the researchers were not homeopaths and did not know the principles of prescribing homeopathic medicines.
Later, a pronounced placebo effect was described in chronic pain syndrome, chronic fatigue syndrome, arthritis, headache, allergies, arterial hypertension (in some cases), insomia, asthma, chronic digestive disorders, depression, anxiety, Parkinson's disease. Under the influence of a placebo, an excess of leukocytes appeared in the blood of a person and the level of proteins and lipids decreased.
The placebo effect is a significant boost in clinical conditions such as pain, mental illness, hypertension, obesity, and perimenopause.
A case was recorded when a patient suffering from Parkinson's disease received a placebo, considering it to be another drug. As a result, his tremor significantly decreased. This result surprised the doctors who conducted the experiment so much that they even suggested that there was some substance in the placebo milk sugar tablet that caused such a pronounced therapeutic effect. However, mixing the substance that is part of the placebo into the milk did not cause any therapeutic effect, since the patient did not know about it. The placebo worked only when the patient believed he was taking the medicine.
During a study of mild psychiatric depression, patients had their medications replaced with a placebo. The results were exactly the same as with medication. In 25% of individuals, the improvement was so pronounced that they were recognized as completely healthy and were forced to be excluded from the group on which the effectiveness of real drugs was tested.
For a number of years, the National Institute of Geriatrics in Bucharest has been conducting a so-called double-blind experiment to test a new drug that enhances the activity of the endocrine system, which, in turn, can increase the chances of longevity. The experiment involved 150 people aged 60 years who lived in approximately the same conditions. They were included in three groups of 50 people. The first group was given nothing, the second received a placebo, and the third received a new drug. Surveys were carried out year after year. The indicators in the first group coincided with the data typical for Romanians of this age. In the second and third groups, taking placebo and the drug, there was a significant improvement in overall well-being, about the same level of health and a lower mortality rate compared to the first group.
The placebo effect was convincingly demonstrated in one of the first studies on the effects of anabolic steroids (J.H. Wilmore, D.A. Costill, "Physiology of Sports"), when 15 athletes who had been involved in strength training loads over the previous two years agreed to take part in an experiment involving the use of anabolic steroids in the process of strength training. They were told that those who achieved the maximum increase in strength during the 14 months of the preliminary training period would be eligible to participate in the second phase of the experiment using anabolic steroids. The subjects were told that they would take 10 mg of Dianabol (an anabolic steroid) daily, when in reality they were given a harmless drug as a placebo. Data on the development of strength were recorded within 7 weeks before the start of placebo consumption and during 4 weeks of its use. It turned out that the increase in strength during the placebo period was significantly higher. Study participants improved their performance by an average of 10.2 kg (2%) during the trial period and by 45.1 kg (10%) during the placebo period. This corresponded to an average increase in strength of 1.5 kg per week during the pre-period and 11.3 kg per week during the placebo period, i.e. almost 10 times.
One study examined the ability to predict the occurrence of recurrent depression from the nature of the primary response. Patients who were treated with fluoxetine for 12-14 weeks were then switched at random to treatment with either placebo or fluoxetine. At the same time, patients who initially responded positively to placebo responded similarly to the continued administration of placebo and to fluoxetine. At the same time, those who received the true cure responded more strongly when switched to a placebo.
It has been found that the placebo effect can occur even when patients know they have been given a sugar pill. In a study conducted at Johns Hopkins School of Medicine, 15 participants receiving outpatient treatment for an anxiety disorder received one sugar tablet per week. At the same time, they were openly told that these were sugar pills and that they helped many people. Of this group, 14 patients reported that their anxiety was significantly reduced; 9 - directly associated the results with taking the pills; 6 - suspected that the tablets contained active ingredients; 3 - complained of side effects: blurred vision and the appearance of dry mouth (such side effects are observed when taking certain psychotropic drugs).
Scientists have proven that placebo has a stable analgesic effect. Many double-blind trials have been conducted to test the effectiveness of placebos in relieving pain. Pain reduction with placebo was 55% of that achieved with morphine.
The SYDNEY study examined the efficacy of a-lipoic acid in patients with diabetes mellitus. Patients were in the hospital for a whole month, which made it possible to normalize nutrition, daily routine, physical activity and hypoglycemic therapy. Positive neuropathic symptoms were chosen as the main criterion for the clinical efficacy of the drug due to the fact that they are the first to disrupt the quality of human life. It is known that the sensations of patients are placebo-dependent, especially "shooting" pain and burning. A decrease in the severity of these symptoms with placebo was noted in more than 30% of patients. That is why the placebo effect in the study was minimized by the presence of an introductory (run-in) period and the presence of a comparison group receiving placebo. However, analysis of the dynamics of scores on a special scale (TSS) for individual symptoms showed that in relation to "shooting" pain, burning and paresthesia, the placebo effect was undoubtedly present (despite the run-in period). The only symptom that was actually insensitive to placebo was a feeling of numbness. In this regard, it is extremely important that the improvement was obtained using a different scale (NISLL), which does not show a significant change when using placebo. The decrease in the number of points on this scale after treatment was mainly due to revival or the appearance of reflexes and, to a lesser extent, due to an improvement in the state of sensitivity of various modalities.
Mechanisms of the placebo effect. Many experts believe that the secret of the placebo lies in self-hypnosis. However, this hypothesis does not explain many of the oddities of the placebo effect, such as its geographic selectivity. Experiments have shown that at different geographical latitudes, the percentage of successful exposure can differ quite sharply.
Some scientists view the placebo effect as a form of hypnosis. It has been proven that the placebo effect increases in direct proportion to the intensity of suggestion. Suggestion itself means the ability to succumb to the influence of words, to realize them in behavior, to bring them to life. The effectiveness of hypnotherapy in any disease is also known as a method of psychoprophylaxis.
It has been proven that the expectation effect is also important in the manifestation of the placebo effect. Three treatments were studied in three groups of study participants: intravenous morphine for pain after thoracoectomy, intravenous diazepam for anxiety after thoracoectomy, and subthalamic nucleus stimulation for idiopathic Parkinson's disease. In each group, some patients were informed about the treatment, while others were not. In all groups, the effectiveness of treatment was higher when patients were waiting for the procedure.
The "expectation" of patients influences the effect of the placebo and the active substance. Asthmatic patients who believed the inert substance to be a bronchodilator or bronchoconstrictor responded accordingly. It has been demonstrated that the "expectation" of patients changes or even distorts the action of some pharmacological agents.
James Frazer's The Golden Bough and Harry Wright's Witness to Witchcraft provide many vivid examples of the psychological power of placebo effects in primitive tribes. “Once, for example, it happened that a New Zealand leader of high rank and great holiness left the remnants of his food on the side of the road. After his departure, a slave, a hefty hungry fellow, arrived in time, saw the remaining food and, without asking, ate it. Before he had finished eating, he was told with horror that the food he had eaten belonged to the leader. I knew the unfortunate criminal well. He was a man of remarkable courage, who covered himself with glory in intertribal wars, the traveler said, but as soon as the fateful news reached his ears, he began to experience convulsions and abdominal cramps of exceptional strength, which did not stop until his death, which followed at sunset of the same days..."
A significant role in the implementation of the placebo effect is played by the personality of the doctor, his experience, qualifications and ability to positively interact with the patient. Receiving a placebo from a doctor and believing that this is a medicine, the patient experiences relief. With prolonged use of the same medication, a kind of conditioned reflex occurs. Apparently, therefore, the placebo effect is more often determined in chronically current diseases, as well as anxiety and pain syndrome.
Do mental factors alone determine the placebo effect?
One study compared placebo effects in 70 patients in the treatment of three anxiety disorders. Patient responses to and expectations of treatment were studied in three randomized controlled trials. As a result, it was found that patients with obsessive-compulsive disorders responded much less to placebo than those with generalized social phobia or panic disorder. These data cannot be explained by different patient expectations.
A placebo effect study was conducted in individuals suffering from chronic depression. 25 of them received antidepressants (fluoxetine and venlafaxine) for 8 weeks, 26 received empty tablets. The results of treatment were assessed by the condition of the patients, as well as by the results of encephalographic studies characterizing the activity of various parts of the brain. Significant improvement was noted in 13 patients (52%) treated with medication and 10 patients in the placebo group (38%). This effect was accompanied by fundamentally different changes in brain activity. Thus, antidepressants predominantly activated the prefrontal area of ​​the brain responsible for the emotional state of a person, and the placebo had only a general stimulating effect on the brain, that is, it did not so much relieve depression as it contributed to a general increase in mental activity. “Physicians have known for years that even sham treatment improves patient outcomes,” said Edru Leichter, lead researcher. “Our results only confirmed the assumption that the placebo effect, in its mechanism, has nothing to do with conventional treatment. Perhaps we can use it for our own purposes, combining it with classical methods of therapy.”
A number of publications have concluded that natural opioids (endofins) play a significant role in placebo-induced analgesia. It has been found that placebo-induced analgesia is partially reduced after administration of the opioid antagonist naloxone. Researchers at the University of Michigan measured the activity of the brain's β-opioid system, which is part of the body's natural pain-relieving system and is involved in the transmission of pain signals from one nerve cell to another. We examined 14 healthy male volunteers who were injected with saline solution in the jaw. For 20 minutes, the participants had to record how severe the pain was every 15 seconds, estimating it on a scale of one hundred. They recorded their feelings of pain, and then summed up the scores. In randomized trials, some volunteers were given painkillers (analgesics) while others were given a placebo. All participants in the experiment, who expected to receive the medicine, but received a "dummy", increased the activity of the endorphin system of the body. There was activity in four permanent brain regions, however, activity in other brain regions also matched the volunteers' description of pain. For example, activity in the dorsolateral prefrontal cortex correlated well with expectations of a drug's analgesic effect. Placebo participants reported a reduction in pain. Using positron emission tomography, it was shown that after taking the placebo pill, the human brain began to produce more natural opioids. The authors hypothesized that the opioid system of the brain is involved in the formation of the placebo effect: “These data deal a serious blow to the idea that the placebo effect is purely psychological, devoid of a physical basis. We saw firsthand how the endorphin system was activated in pain-related areas of the brain. Similar activity was noted when the volunteer was told that he had received pain medication. However, the response of people who were switched from real drugs to placebos was not always the same. The researchers divided the patients into "little reactive" and "very reactive" (in whom pain was reduced by more than 20%). “What determines such a different response is not yet clear, this will be the subject of further research, during which it will be necessary to identify changes associated with age, gender and other factors, such as the presence of diseases,” the scientists note. According to some experts, patients who respond to placebo have an innate quality of the brain - self-regulation, which is most likely short-lived.
In another study, researchers at the University of Texas demonstrated the existence of a placebo effect in depressed men who took Prozac or placebo for 6 weeks. Comparing positron emission tomography scans of the patients' brains, they found that in both groups there was an increase in activity in the cerebral cortex - in the "thinking" part, while it was observed in the limbic part that controls emotions. In 15 people, there was an improvement in neurological symptoms, and 8 of them took a placebo. The differences in the responses of the compared groups of patients that took place were that changes in both the brainstem and the hippocampus were observed in those taking Prozac. The authors suggest that reduced metabolic activity in the brainstem and hippocampus probably maintains positive cortical or limbic changes, contributing to a longer lasting effect of the drug.
The placebo activates the function of the cerebral cortex, and this, in turn, stimulates the endocrine system and the production of hormones of the adrenal cortex, which have pronounced anti-stress and anti-inflammatory effects.
As you know, Parkinson's disease is associated with a reduced level of dopamine in the blood, and drugs that stimulate the production of this substance are used to treat it. However, when the six patients began to receive injections of a simple saline solution instead of medicine, their health continued to improve, as before. As the tests showed, as a result of the procedure, the level of dopamine in the blood of these patients increased by more than two times. Of course, the patients themselves did not know anything about this and out of habit expected that the injection given by the nurse would bring them relief. These studies were carried out by Professor John Stoysle and colleagues at the University of British Columbia.
British radiologists studied the effect of apomorphine and placebo on the release of dopamine in patients suffering from parkinsonism. It turned out that the introduction of saline causes the same effect as the introduction of the drug. Using positron emission tomography, it was found that placebo stimulates the biosynthesis of dopamine in the striatum. The expectation of relief plays a key role in creating the placebo effect, regardless of the type of disease. As soon as the expectation appears, the brain launches other mechanisms that target the focus of the disease. This confirms the fact that the patient is able to transform the hope for healing into tangible biochemical reactions.
Placebo therapy. The researchers of the placebo effect quite reasonably asked the question: if placebo pills for some diseases are not much inferior in effectiveness to a real drug, is it not better to use it? However, is it ethical? An article published in the British Medical Journal that Israeli doctors use (and not without effect) placebos could not help but attract attention. It turned out that about 60% of doctors, in order to satisfy the "unjustified" demands of patients, use in their medical practice substances that have nothing to do with a drug in the usual sense. Therefore, one can resort to a placebo in order to “not withhold help” and not harm with an unnecessary drug. A placebo is used, so to speak, for a diagnostic purpose: “it will help” means that the disease is imaginary.
Published research results indicate a high frequency of cases of cure with placebo: headache - 62%, colds - 45%, rheumatism - 49%, motion sickness - 58%, intestinal disorders - 58% of cases. However, there were also low cure rates: sleep disturbances - 7% of cases, bronchial asthma - 5%, epilepsy - 0%, mental disorders - 0%. This indicates that the medicinal properties of drugs are actually much lower than commonly believed, since their testing did not take into account the placebo effect.
In the last 10-20 years, interest in placebos has increased significantly. Particularly revealing were studies conducted at the University of California, which amounted to a volume of articles on placebos. These trials showed that a placebo can act like a drug (sometimes even a powerful one) and also cause changes in the reactions that occur in the body.
The placebo effect occupies a special place in the treatment of mental and psychosomatic diseases.
There is no unified theory of the occurrence of psychosomatic diseases. Diseases of this kind are considered the result of the devastating effects of stress. At the same time, the stressful state is fixed in long-term memory, that is, it is able to remind of itself years later. Scientists believe that the frequency of psychosomatic disorders in general medical practice is up to 60%.
Back in the 18th century, during his medical experiments with magnetism, Anton Mesmer noticed that very often relief and recovery of patients come even without touching the magnets he used to treat (once he simply forgot them at home).
The significance of the impression that a doctor makes on a patient is well known from history, from the experience of G.A. Zakharyin (1829-1897). This eminent physician used the following setting during his consultations with wealthy patients. After the examination, the professor, alone in a special darkened room, pondered the diagnosis and treatment. At this time, complete silence was to be observed in the house. From such a consultation, the impression made on the patient and his relatives was favorably reflected in the results of treatment and allowed the doctor to achieve amazing success.
In 1807, American President Thomas Jefferson wrote in his diary how one of the most successful physicians known to him admitted that in his practice "he used more bread-balls, drops of colored water, and powder of ash than other remedies combined." Without judging the doctor in the slightest, the president called the practice "a good lie."
I would like to recall the famous therapist of the 19th century M.Ya. Mudrova, who treated with "special" powders with the names "golden", "silver", "simple". The names corresponded to the color of the paper in which the product was wrapped. These powders had miraculous effects, cured many diseases. After the death of the doctor, it turned out that they included well-ground chalk. The delight and joy with which the patients took these "medicines" was more useful than the drugs themselves. The great practitioner of placebo therapy wrote: “The art of the doctor lies in creating a “soulful” medicine that would console the angry, calm the impatient, stop the mad, frighten the impudent, make the timid bold, the frank - hidden, trustworthy - desperate.
Trust in the doctor is an essential component of the placebo effect. When the patient is afraid of something or something hurts, his senses are heightened. Meanwhile, the discussion continues among physicians who consider it unethical to deceive the patient, and among those who rely on Plato, according to whom "lying does not benefit the gods, but is useful to people as medicine." It should be noted that even a non-specialist, resorting to placebo-type effects, can act as a healer.
White lie, placebo effect - the basis of "shamanic medicine" - so say the opponents of the use of placebo in medical practice. Proponents of placebo therapy are no less categorical: in a number of diseases, a “dummy” can successfully replace drugs, and if we take into account the growing high cost of new drugs, then placebo is economically beneficial. However, there is a golden mean; adherents of this position believe that placebo is an interesting field of medicine that requires attention and study.
Critical views on the placebo effect. Some authors have expressed doubts about the existence of the placebo effect. There have been numerous discussions on this topic, which continue to this day.
Employees of the University of Copenhagen and the International Medical Center, which specializes in assessing the quality of clinical experiments, analyzed the results of 114 published studies, which involved 7500 patients suffering from 40 different diseases, including arterial hypertension, asthma, pain syndrome, depression, schizophrenia, epilepsy. They concluded that placebo had no significant effect on secondary administration and might have little subjective benefit in long-term treatment of the disease. Scientists have not found substantiated evidence for the generally accepted notion that, on average, the condition of one in three patients who are given pseudo-drugs improves after taking them. The researchers became interested in where this figure came from, and it turned out that the authors of all the articles in which she met, refer to the work of G. Beecher. After analyzing the data of this work, they found a number of shortcomings. First, the range of disorders in which the placebo effect was confirmed by the results of studies was limited only to various types of pain syndromes (after surgery, with headache, angina pectoris and osteoarthritis). Only one study found to support placebo efficacy for coughs, colds, motion sickness, and anxiety. Second, in most of the trials described, there was no control group that received no treatment at all. Therefore, the presence of a placebo effect cannot be judged with certainty from these results. In addition, in one of the studies, some patients did not receive treatment, and there was no difference between them and the placebo group.
The reason for this misconception, scientists believe, is the misinterpretation of statistical data. The fact is that in many diseases the condition of patients in itself either improves or worsens, and these fluctuations are erroneously attributed to the action of a placebo. Success from a placebo may coincide with the natural (positive) course of the disease. This fact, well known to physicians of the past, is almost forgotten in modern clinical practice.
It is known that in many diseases the condition of patients does not change monotonously, but varies, and periods of deterioration are replaced by periods of improvement. It is these natural variations in the course of the disease that are mistaken for the placebo effect. Hippocrates wrote about this: “The disease reveals paroxysms and conditions both according to the time of year, and upon the return of its periods, one in comparison with the other, they happen daily, or every other day, or after a long time.”
Studies comparing treatment outcomes not only with placebo but also with no treatment at all have shown that placebo and no treatment at all often have almost the same effect on patients.
Medical statisticians at the Houston Cancer Center backed the Copenhagen researchers because of the well-known statistical observation that a patient who feels terrible today will almost always feel better the next day, no matter what doctors do. Agree with the results of the Danish study and scientists at the Center for Biomedical Ethics at the University of Virginia, who consider placebo effects a medical legend.
At the same time, other medical statisticians do not find this work convincing enough, since the statistical method of meta-analysis used by the Danes can give erroneous results. The placebo efficacy may have been exaggerated quantitatively, but in many cases it was still quite significant. D. Evans notes that if they had carefully analyzed the data, they would have found that the effect when using a placebo was not statistically significant only according to the results of studies that used a binary scale (the presence of a positive or negative effect). On the contrary, in those studies that used a continuous scale with placebo, there was a pronounced statistically significant positive effect. The range of states studied in the mentioned test was very wide - their number was estimated at four dozen. Particularly significant is the fact that the placebo acts differently in different diseases, that is, it is not a panacea, not a universal medicine.
The Copenhagen researchers acknowledged that in some cases they also noted a weak placebo effect, manifested, in particular, in patients' subjective judgments of the pain they had experienced, but rated it as insignificant and almost imperceptible. Most likely, these are subjective delusions: some patients instinctively want to answer the interviewing doctor that they feel like they are better. Meanwhile, from the point of view of scientific (evidence-based) medicine, it would be logical to find out whether a placebo really causes any significant changes in the course of any diseases, and to build an attitude towards the use of a placebo based on scientific data. Such a study is quite difficult to conduct, since the use of a placebo is difficult to separate from the accompanying actions of medical personnel. Therefore, the placebo effect is usually identified with the totality of conditions that accompany the provision of treatment.
It has been suggested that the placebo effect also occurs with conventional therapy. Thus, the condition of patients with depression who received pharmacotherapy improved by 33% after a certain time compared to those who were prescribed a placebo. At the same time, those who took a placebo had a 200% improvement compared to patients who were on a waiting list and received no treatment at all. According to the authors, about 25% of the severity of the effect of antidepressants is due to spontaneous remission, 50% - to the placebo effect, and only 25% - to the pharmacological action of the drugs. However, if an additional 25%, which gives the actual effect of antidepressants, lead to the fact that the condition of patients begins to be characterized not by an average, but by a slight severity of functional disorders, then the effect of pharmacotherapy is very important.
A study was made of the significance of the so-called positive and negative consultations in persons with functional pathology. In the first case, the patient was told that he did not have a serious illness and that he would get better in the near future; in the second - that the nature of the disease is not entirely clear. In both groups, one patient was given a placebo, while the other was given no medication. Recovery occurred much more often and faster in the first group; in both groups, there was no difference in treatment effect between placebo and no drug participants. From this it follows that in everyday practice the placebo effect is quite common and largely depends on the personality of the doctor.
Meanwhile, these data are not very convincing opponents of placebo. Thus, Tad Kapchuk, a professor at Harvard University who has participated in many clinical studies using placebo, states: "Although inert pills have shown little effectiveness in relieving pain, I see no justification for using them outside of clinical trials." He insists that in future studies, the placebo effect should be compared not only with the effect of real drugs, but also with no treatment at all.
What effect the imitation of the therapeutic effect - "dummy" has, is practically unknown today, because there are very few studies comparing the state of those who take a placebo and those who receive nothing but diagnosis and observation. Moreover, it is impossible to study the natural course of the disease without intervention in modern conditions, since not a single ethical committee will agree to conduct such studies.
Placebo in clinical trials. In the 19th century, medicine was dominated by the practice of evaluating the effectiveness of treatments on the basis of pathophysiological theories and the physician's "impression" that the drug or treatment was helping the patient. Already in the 30s of the last century, Bradford Hill introduced a randomized selection of patients both in the main group and in the control (comparison) group in determining the effectiveness of the test drug. Decisive was the decision of the US Food and Drug Administration (FDA), adopted in 1962, that new drugs should be subjected to clinical trials before their widespread use. Evidence of efficacy subsequently began to be obtained through randomized placebo-controlled trials, placebo control became the gold standard for clinical drug trials.
In recent decades, evidence-based decision making, which combines individual experience with the results of clinical research, has become widely accepted in clinical practice. The rapid development of evidence-based medicine methods also introduced physicians to the term "placebo", used in clinical trials of drugs as indispensable evidence that the test drug is better than "dummy".
Clinical studies of new drugs usually compare two groups of patients in whom the natural course of the disease and the nonspecific effects of therapy would be approximately equivalent. When active treatment is given to one group and placebo to the other, the differences are attributed to the specific effect of the therapy. Over the past 40 years, using this method, high results have been achieved in evaluating the effectiveness of many drugs.
Since the 1970s, placebo and double-blind trials have been indispensable for evaluating the efficacy of new drugs, testing the efficacy of established drugs, and comparing similar drugs. A distinction is made between an open method, when the drug is known to all participants in the treatment or trial, and a simple blind method, when the patient does not know which medicine he is taking. In a double-blind method, a test drug is compared with its placebo counterpart, but neither the test subjects nor the experimenters know which of these drugs is used for protocol studies. Patients should not be aware of this because their expectations affect the outcome of treatment; doctors - because they can involuntarily influence the well-being of the subjects, who catch the slightest change in the behavior of the doctor. Only a third party has complete information. The double-blind method eliminates the effect of bias on the results of treatment, since the doctor cannot have a psychological impact on the patient and it is not enough to objectively evaluate the effect of therapy. The effect of a medicinal substance is considered to be scientifically confirmed if the difference between the measurements of the effects of the study drug and its counterpart reaches a statistically significant value. Medicine as a science is gradually replacing medicine as an art. That is why it is necessary to apply treatment, the effectiveness of which has been proven by objective data.
However, the use of a placebo as a comparator to prove the benefit of a new drug creates a number of problems in itself. For example, can a placebo be used in a drug trial for the treatment of acute and severe conditions (anaphylactic shock, ketoacidotic coma) or cancer? Is it ethical to prescribe a placebo to one group of cancer patients and a new, known effective drug to another? Based on this, the ethical committees of European countries are very exacting in the design of clinical trials, requiring that the use of a placebo be irreproachably justified. Thus, according to the Declaration of Helsinki, in any medical research (including clinical trials), all patients, in particular those included in the control group, must be properly examined and receive appropriate treatment. Refusal in some pathological conditions from the use of placebo, when patients (from the control group) cannot be left without treatment, should be considered ethically justified. If the effectiveness of the drug is already established, a placebo-controlled trial should not be carried out even if required by the licensing authorities.
Modern requirements for conducting GCP (Good Clinical Practice) clinical trials include mandatory compliance with ethical standards, which, in addition to the decision of the ethical committee to conduct the trial, also include the informed consent of the patient. However, the latter, as some studies show, can affect the outcome of the test. If there is a worsening condition after placebo, the patient should be withdrawn from the study or transferred to active treatment in the same trial. There are strong arguments for the fact that participants in clinical trials in many cases are aware that they are prescribed a "pacifier". They make similar conclusions based on the absence of side effects. Thus, in one clinical study comparing the outcomes of the use of two antidepressants and a placebo, 78% of patients and 87% of doctors correctly identified who took the drugs and who - their imitation. In other data, in 23 of 26 studies, the identification of patients treated with active and inactive drug was more accurate than random guessing.
In order to distinguish between the true pharmacological effect and the placebo effect when taking the drug, it is proposed to use four parallel groups instead of two. In addition to those taking a drug, an inactive drug, and no treatment at all, an "active placebo" group can be formed. In this case, the patient also does not receive the study drug, but takes a drug that mimics its side effects. For example, when testing antidepressants, atropine can be used. In this case, the subjects will feel one of the often developing side effects - dry mouth, and it will seem to them that they are receiving a specific treatment.
Conclusion. The placebo problem seems to be somewhat broader than the actual clinical trials. There seems to always be a patient expectation component to the positive effect of a given drug, just as there is to a placebo. This component of expectation, hope for an effect depends not only on whether an outwardly inert, indifferent substance is similar to a real medicine in color, shape, smell. In anticipation of the effect, a large role belongs to the doctor himself, his relationship with the patient.
There are still more questions than answers about the placebo mechanism of action. Although it is generally accepted that the secret of the placebo lies in autosuggestion, this assumption does not explain many of the oddities of its action. Already now there are many systems that are based only on the effect of faith. However, the task of scientists is to learn how to use the mechanisms of self-healing without taking a placebo. Research in this area is still ahead. Irving Kirsch, a psychiatrist who has studied the placebo effect for many years, said: “The only thing we can say for sure is that we don’t know anything about it.”
Placebo is an extremely interesting medical phenomenon. It is likely that the essence of placebo in the future will make it possible to understand how the body of a person who believes in a medicine heals itself. “The only thing we know for certain about the placebo effect is that it is not caused by sugar pills because they are inert,” writes Daniel Moerman, a thirty-year placebo researcher.
In recent years, interest in studying the placebo problem has revived somewhat. Thus, the decision of the US National Institutes of Health in the budget year approved 14 new clinical studies aimed at studying the mechanisms of placebo effects on the patient's body.
Based on the data accumulated to date, it can be assumed that the placebo effect is present in any treatment intervention and its importance should not be underestimated. This is stated by Ann Arrington, a professor at Harvard University and author of The Placebo Effect.
So, based on our own many years of experience in studying the general principles of pharmacotherapy, we propose to single out the following body responses to the effects of a drug:
1. Psychosomatic (if there is a placebo effect).
2. Pharmacological (pharmacodynamic).
3. Metabolic (associated with the metabolism of the drug in the body).
4. Response-nonspecific (non-specific reaction in response to the introduction of a foreign substance).
5. Response-physiological (for any change in pathophysiological processes in the body, a reverse specific reaction occurs).
The features of the manifestation of these reactions depend on the dose of the drug (strength of exposure), the frequency and pattern of the pharmacological effect, the characteristics of the body to respond to it, depending on the stage of development of the pathological process, as well as on the constitutional-genetic, age and gender characteristics of the body to perceive the impact and respond to it .
All these questions require deep fundamental study. At the same time, modern medicine has a theoretical justification for the practical use of only pharmacological effects and does not take into account the entire versatility of the body's response to it.

This effect has been established by physicians. It is based on a deliberate or unconscious suggestion by a doctor or experimenter that a certain factor (drug, course of action) should lead to the desired result. The faith of the subjects or patients can really work wonders, although the factor itself does not play any effect. If patients expect that the drug should improve their condition, then they really experience changes for the better. In medicine, placebo (Latin placere - like) means a drug that has no medicinal properties ("fake drugs"). The term "placebo effect" was introduced into scientific circulation by the American physician Henry Beecher in 1955, who found that about a third of patients recover from "dummy" pills that do not contain active ingredients. Serious study of the placebo effect began during World War II. When there was a shortage of painkillers in the frontline hospital, Henry Beecher, an anesthesiologist, became convinced that in some cases an injection of saline had almost the same effect as real medicine. After returning from the war, a doctor with a group of colleagues from Harvard University began to study this phenomenon. He summarized the results of his research in 1955 in the article "Strong placebos." The strongest factor in placebo effects is the belief of the doctors themselves and staff in the power of drugs. A lot of double-blind experiments have been conducted in which a placebo effect has been demonstrated. One of them is a textbook case of studying the effectiveness of reserpine. In 1953, psychiatrist E. Mendel worked at the St. Elizabeth Psychiatric Hospital near Washington in the department that treated people from Puerto Rico and the Virgin Islands. Most of the patients were hospitalized due to bouts of hostile and aggressive behavior. Some of them were so dangerous that they were kept in special shirts, and Mendel was accompanied in the hospital by two guards. Communication was also difficult because the patients did not know English, and Mendel did not know Spanish. At that time, a new tranquilizer, reserpine, became popular, which gave good results precisely for such patients. Hospital leaders decided to test these drugs, and with the help of a special double-blind method. Patients were not informed that some received real medicines, while others - the so-called "pacifier" (simply sweet pills). Doctors did not know which of the patients received the drug, and which only thought they were receiving it. Mendel told patients about the new drug, its effectiveness, speed and lack of side effects. The patients knew the participants in the study. The experiment lasted several months. However, very soon Mendel came to the conclusion that the drug has a very positive effect on patients. The patients became calmer, communicated more affably with the doctor, and soon he allowed the straitjackets to be abandoned. Mendel himself experienced a spiritual upsurge, he believed that reserpine would revolutionize psychiatry, especially with regard to aggressive patients. However, he was shocked when he found out that his patients received exactly a “dummy.” After analyzing all the events, Mendel realized that positive changes had occurred precisely because of his behavior and kind attitude towards patients. The doctor believed that his patients receive reserpine and therefore become calmer, they have friendly looks, smiles, gestures. Mendel everywhere saw signs of an improvement in the mental state of patients. The doctor realized that the patients simply began to react to his calm attitude, which was the result of the doctor's confidence that reserpine was working. He simply began to treat his patients better, and they responded with friendly behavior, they were pleased that they were treated as full-fledged people. Manifestations of the placebo effect are associated with the patient's unconscious expectation, his ability to be influenced, and the degree of trust in the psychologist. This effect is used in studying the role of suggestion under the influence of drugs, when one group of subjects is given a real drug, the effect of which is being tested, and the other is given a placebo. If the drug really has a positive effect, then it should be more than from the use of a placebo. The typical rate of positive placebo effect in clinical trials is 5-10%. In studies, it is also easy to cause a negative nocebo effect, when 1-5% of the subjects experience discomfort from taking a “dummy” (allergies, nausea, impaired cardiac activity). Clinical observations indicate that nervous personnel cause nocebo effects, and the administration of anxiety-reducing drugs to patients significantly reduces anxiety among doctors themselves. This phenomenon has been called "placebo rebound." For especially emotional patients who are prone to self-hypnosis, doctors attribute neutral drugs that will help improve the person's condition and avoid taking unnecessary drugs. The positive effect of homeopathic medicines is partly explained by the placebo effect. It works not only in an experiment, but also when imitating a certain medical procedure, under the influence of a conversation, when a person’s psychological reserves are mobilized. Even when using perfectly studied drugs, they try to trigger the placebo effect. Bright and large pills work better than vague and small ones, and drugs (“bioequivalents”) of well-known companies give a greater effect than drugs from modest manufacturers with the same composition. The basis of the placebo effect is the suggestion that the drug has a certain effect, and the expected effect appears because the brain begins to stimulate the production of endorphins, which partially replace the effect of the drug, and the "mobilization effect" also works - increased immunity, mobilization of the body's defenses. Manifestations of the placebo effect depend on the level of self-hypnosis and the physiological ability to form the necessary chemicals. Doctors have long used the placebo effect. Famous therapist of the XIX century. M. Ya. Mudrov treated patients with special powders with the names "golden", "silver", "simple". These names corresponded to the color of the paper in which the medicines were wrapped. Mudrov's powders cured many diseases, had a real miraculous effect. After the death of the doctor, it turned out that it was just ground chalk. Therefore, it is clear that psychological perception, emotions, trust in the doctor had a healing effect. The doctor himself, a practitioner of placebo therapy, wrote: “The art of the doctor lies in creating “medicines for the soul” that would console the angry, calm the impatient, stop the violent, frighten the impudent, make the shy bold, frank - unsociable, reliable - desperate. The effect of the placebo effect enhances the authority of the doctor, so any medicine from the hands of a famous luminary has a much more effective effect on patients than those prescribed by a local doctor from a local clinic. According to research, placebo affects all people, but most of all, extroverts who are anxious, dependent, labile, flexible and trust their doctors. Placebo non-responders are more likely to be introverted, distrustful, and suspicious. More exposed to the placebo effect are neurotic people with low self-esteem, insecure, who tend to believe in miracles. In medical practice, it has been confirmed that placebo works better for people with mild psychosomatic disorders, such as mild insomnia or minor depression. It has been established that the placebo effect can occur even if patients know that they are simply receiving neutral pills. In a study conducted at Johns Hopkins Medical School, 15 people were treated for anxiety and received a sweet pill once a week. They were frankly explained that these were “dummy”, however, they noted that they help some patients. After completion of treatment, 14 patients reported that their anxiety significantly decreased, of which 9 believed that the improvement was due to the action of the pill, 6 suspected that the pills contained active substances, 3 complained of side effects (impaired vision, dry mouth ). Such complaints are typical when taking certain psychotropic drugs. Since 1970, placebo and double-blind testing have been mandatory for evaluating the effectiveness of new drugs and comparing similar ones. Over the past 10-20 years, the interest of both psychologists and physicians in placebo has grown significantly and its study continues.