Placebo and nocebo: rules of self-healing. What is the nocebo effect? Mechanisms of placebo formation

Let's talk about nocebo. In the case of the placebo effect, the situation seems reasonably clear. Simplifying a little, we can say that we are talking about the fact that the patient, swallowing a sugar tablet, has the hope that thanks to this he will stop having a headache, and the pain will recede.

However, what happens if the patient activates negative rather than positive expectations? Persuaded by his doctor or family, he finally swallows a pill, not necessarily a sugar pill (since we already know that a placebo can also be a pharmacologically active substance), but he thinks that the pill will harm him rather than help him.

Or, if his condition improves, then we will continue to deal with the placebo effect, or not? What if the patient’s condition worsens?

As Helen Pilcher writes, one Sam Schumann was diagnosed with liver cancer and had about a month to live. The doctor told him about this diagnosis.

The patient actually died a month later. But an autopsy revealed that a catastrophic mistake had occurred. Schumann's liver was in excellent condition, and no tumors were found in other parts of his body.

Would the patient have remained alive if not for the verdict he heard from his doctor? It is impossible to say with all certainty, but it looks very plausible.

In the psychological and medical literature the term “ nocebo" It is of Latin origin and literally translated means “ I will do harm».

As Bombel emphasizes, fierce (often fruitless) debate continues in the literature on this issue over the meaning of the term “ nocebo" and its relationship to " placebo" Robert A. Hahn offers a simple taxonomy that arises from the intersection of a patient's expectations of a therapy or other intervention and the outcome of those interventions.

Nocebo effect and placebo effect

Placebo effect and nocebo effect. We deal with the first in the case of positive expectations of the patient and a beneficial result of therapy, with the second - when both expectations and results are negative.

Khan is considering two other possibilities. In relation to positive expectations, but negative results, he uses the term “placebo side effect”, and for the opposite situation, i.e. negative expectations but positive outcomes, he reserves the term “nocebo side effect.”

Therefore, we see that the key for this researcher are the expectations that the subject formulates. This approach seems convenient and logical. However, it should be emphasized that this is not consistent with the original nocebo approach, where the emphasis was on outcomes: if they were negative, then this was enough to talk about the nocebo effect.

Khan's proposal also raises other problems. This researcher seems to implicitly accept that the placebo effect can only be four states of affairs: placebo and nocebo effects, as well as their side effects.

At the same time, firstly, there may be a lack of any effects, and secondly, the effects may be different. This first situation is further complicated by the fact that it is relatively easy to talk about the emergence of such a state of affairs when no active therapeutic actions have been taken in relation to the patient. If active therapy was carried out on him, then it will not be so simple.

Accordingly, it is difficult to clearly separate active effects from placebo. Other problems arise when the patient formulates negative expectations and no changes occur. Is this enough to talk about a nocebo side effect, or not?

In relation to the second question, it should be noted that people can evaluate their condition, taking into account many different parameters, of which some may improve, others may worsen, and others may remain unchanged. Therefore, the result of a placebo can be both a placebo effect and nocebo effect(for example, the patient’s head stopped hurting, but his palms began to go numb), and also - if we use Khan’s terminology - side effects of placebo and nocebo.

But it seems that it is better to return to the original understanding of “nocebo” as a placebo effect that manifests itself in the form of negative changes in the subject’s state. The departure from the category of expectations in understanding placebo is even more justified due to the fact that expectations are only one of the possible mechanisms of placebo. To the reader who has shown greater interest in problems of precise definition of the concepts “nocebo” and “nocebo effect”, I suggest reading Przemyslaw Bombel’s article dedicated to this very issue.

From our point of view, the problem is that although researchers have devoted a relatively large amount of time to writing papers devoted to the very concept of nocebo, very little empirical research has addressed what seems to be the most important thing: the situations in which nocebo effect.

He is known to appear frequently. Depending on whether participants spontaneously report negative states of the body are taken into account, or whether they are asked to indicate which of the negative states presented to them they feel, these rates range between 19% and 71%10.

Brody, citing Honzak, Horatskova and Kulik from 1972, argues that the nocebo effect most often concerns such manifestations as drowsiness, headaches, palpitations and weakness with its associated decrease in blood pressure, increased irritability, insomnia and diarrhea. However, it is unclear why these symptoms are the most common.

Sometimes the nocebo is of a very original nature. Wolf and Pinecki described, for example, the case of a man who repeatedly developed skin rashes in response to taking a placebo (lactose). In studies of oral contraceptives, in turn, it is stated that taking a placebo in a double-blind trial often (in less than 1/3 of the subjects) led to increased nervousness, increased menstrual pain and decreased libido. As an extreme case of the nocebo effect, some researchers point to death as voodoo.

According to Lund, the nocebo effect, as well as the side effects of therapy, depends not so much on the therapeutic treatment itself, but on the patient’s previous experience, on the basis of which he forms specific expectations about the effects of this therapy. However, newer (recent) research shows that in women nocebo actually appears as a result of conditioning processes, while in men it is a result of negative expectations. In both cases, the neurological basis of the nocebo effect is the same: a decrease in dopamine and opioid levels, which would explain why nocebo is so often associated with an increase in the sensation of pain.

Placebos and people

It may seem quite obvious that there are people who are susceptible to the placebo effect and others who are not affected by placebos at all. It is therefore not surprising that almost from the very beginning of research into the placebo effect, attempts have been made to establish a connection between the personality of participants given pharmacologically inactive substances and the effects of these substances. Although it may seem implausible, to date no personality factor has been identified that can effectively predict the response of study participants to placebo.

The impetus for the emergence of researchers' interest in this issue was the work of Jelink. He argued that people with chronic headaches showed a consistently consistent pattern of response to placebos. For some people it has repeatedly acted as an excellent analgesic, for others it has never been effective.

Such results could clearly indicate the existence of individualized susceptibility to placebo effects, and inspired researchers to identify personality or temperamental properties associated with this susceptibility. The first empirical studies on this issue seemed promising.

Lasanya and his colleagues noted that people for whom placebo therapy was effective were more emotionally immature, more internally focused, more religious, and had higher levels of fear than those for whom placebo therapy was not effective.

The relationship between the dispositional tendency to respond to placebos with optimism and placebo susceptibility was also examined. Indeed, if we assume that the origins of the placebo effect lie in the generation of positive expectations, then such cognitive forecasts should be especially characteristic of optimists. However, empirical studies do not provide clear evidence of a relationship between dispositional optimism and placebo effectiveness, suggesting only that optimism plays a role only in specific cases.

In my own research, I tried to identify personality factors that could contribute to the placebo effect. Students from Wroclaw and Opole took part in them.

First, they took a battery of personality tests: the F Questionnaire, which measures authoritarianism; the TES test, which measures egocentrism; the religiosity scale developed by Prengin; test-Spielberger questionnaire, measuring fear as a trait.

Additionally, participants answered the question about how often they turn to pharmacological agents in case of feeling any ailment or illness. Then the students were randomly divided into two groups of unequal numbers. Most of them were subjected to placebo therapy - they were given 7 tablets with the recommendation to take one daily.

The drug (actually consisting of sugar) was presented as safe for health and consisting of completely natural ingredients. Its action was supposed to be to improve mood and increase intellectual abilities, with special emphasis on memory processes and concentration. It was also assumed that the drug reduces the likelihood of headaches in the form of attacks, alleviates fatigue and exhaustion. The remaining participants were in the control group, in relation to which they did not take any action.

At the end of the week (i.e., at the end of therapy in the experimental group), all participants filled out special questionnaires in which they described their condition during the last week and at the moment. It turned out that representatives of the experimental group noted a much better state both during therapy and at its end than participants in the control group.

This indicates the occurrence of a placebo effect. In the area of ​​personality factors as modifiers of the strength of a positive reaction to placebo, not a single statistically significant effect was identified. Also, the tendency to use medications in conditions of discomfort did not differentiate (do not influence) the state of health reported by the participants.

With a certain amount of self-irony, I can say that my research fits well into the series of failures of researchers around the world. Indeed, in reality, it has not yet been possible to identify a single personal factor that would make it possible to well predict the reaction of participants in the area of ​​interest to us.

This is also strange because they tested the role of such different variables as (among others) self-esteem, locus of control, neuroticism, level of self-focus, or authoritarianism. The role of the tendency to lie was also tested (using the Eysenck lie scale), based on the judgment that people tend to present themselves in an exaggeratedly positive light, they lack a look inside themselves.

Such people were thought to be 38 particularly susceptible to placebo effects. However, it turned out that the expected effect not only did not appear, but a (weak) inverse relationship was obtained. Those subjects who scored lower on the lie scale were slightly more susceptible to the placebo.

The discovery of a personality factor (or factors) associated with placebo susceptibility would have enormous practical implications. This would make it possible to describe for which patients suffering from somatic ailments a tablet consisting of powdered sugar or a glass of slightly colored and slightly salted distilled water might be effective.

Some hope in this area can be associated with factors that do not belong to the most frequently studied personal qualities. I mean, for example, suggestibility (and therefore the degree of susceptibility to suggestive messages from other people). There is evidence that this quality is associated, for example, with perceptual sensations or with the belief in accurately remembering certain events.

Hypothetically, it can be argued that the patient's suggestibility is associated with susceptibility to the placebo effect under conditions in which the doctor or therapist skillfully convinces him of the high effectiveness of a drug or other therapeutic intervention. Whether this actually happens can only be predicted by future empirical research.

It is now known that the factor that increases the chances of the placebo effect occurring is the emotional state of the patient. There is fairly good evidence that this effect is more likely to occur when the patient is feeling very fearful or anxious than when the patient is calm. This dependence is usually explained by the fact that the apparent reduction of fear (and this is possible mainly in patients experiencing anxiety) contributes to the emergence of positive expectations, which, in turn, can lead to the release of endogenous opiates.

Published by: B. Dolinskaya. Placebo. Why does something work that doesn't work?

What do we mean when we talk about "placebo"? You've likely come across this term when reading articles about studies where a placebo was used to confirm the effectiveness of the study drug.

We can say that a placebo is a “dummy”, as a result of which a certain positive effect can be observed, and if it turns out to be similar to the effect of using any drug, then the effectiveness of this drug is considered zero. But how do different studies achieve the placebo effect itself? How does it work, what is the mechanism of its application based on, does it act systematically, or does it affect only individual functions?

In order to answer the questions above, we need to take into account another phenomenon - the nocebo effect, which is the opposite of placebo. This concept can be encountered extremely rarely, and in studies that are not aimed at studying this phenomenon, it is usually ignored

Placebo does not only mean taking a substance that has a therapeutic effect without a corresponding pharmacological substrate. The development of the placebo effect is also influenced by social interactions, such as the relationship between the doctor and the patient (the latter’s belief in a favorable outcome of treatment).

Placebo effects are erroneously attributed, for example, to spontaneous remission of a chronic disease; a “feeling of discomfort” that passed over time, which brought anxiety and was subjectively perceived by the patient as a pathology.

In addition, there is a human factor, expressed in the bias of the researcher, making mistakes in conducting an experiment regarding the comparison of the effectiveness of a drug or technique with the placebo effect.

The formation of the placebo/nocebo effect is based on the following mechanisms:

1. The patient's expectation of the effect of taking the medicine:

• Positive/negative expectation: causes a decrease or increase in anxiety levels;
• Anticipation of a positive resolution of the disease: activation of the “reward system”.

2. Training - consolidation of the effect against the background of the experience gained (not necessarily personal, perhaps inspired from the outside).

Both of these mechanisms are not mutually exclusive, but, on the contrary, complement and potentiate each other. The phenomenon of placebo and nocebo is most often clearly manifested in the following conditions:

1. Subjective symptoms accompanying various diseases and pathologies and manifested by disorders of the psycho-emotional sphere, such as:

• increased anxiety, irritability;
  periodic feeling of discomfort, etc.

2. Mental disorders (for example, depression);

3. Pain: acute, chronic (including CRPS);

4. Extrapyramidal disorders (Parkinson's disease, chorea of ​​various origins): placebo/nocebo effects arise due to dysregulation of the dopaminergic system that occurs in these diseases;

5. Diseases of the immune and endocrine systems.

BBpain

About 40-50% of the world's population experiences chronic pain of varying localization and intensity. The characteristics of these pains depend on their primary etiology (trigger factor), as well as individual characteristics, such as the patient’s age, his profession, etc.

About 10% of acute pain cases become chronic. In principle, acute pain is not pathological in itself (with the exception of some cases, for example, pain during traumatic shock), although it brings physiological suffering to a person. Pain caused by the nociceptive component has its own functions: protective and reparative.

At the same time, chronic pain is deprived of these positive effects that characterize acute pain. This is a maladaptive phenomenon in which the resulting chronic pain ceases to be a symptom, but becomes the disease itself.

It is also important that often the same trigger can cause pain through different biochemical pathways, and this determines the need to choose therapy depending on the biochemical profile of pain, rather than its primary etiology.

The occurrence, conduction and perception of pain signals are influenced in a certain way by the central nervous system, and its modulating effect plays an important role both in analgesia and in the process of pain chronicization. The severity of pain symptoms and the occurrence of pain chronicity are determined, among other things, by many subjective and situational factors, such as the level of anxiety and fear, lack of sleep, social behavior, etc. Further in the text, evidence of the influence of subjective parameters on the perception of pain, as well as the possibility of influencing on them.

Neurobiological aspects of placebo and nocebo in analgesia

Placebo and nocebo antagonize each other, changing the activity of various internal systems of the body. One of them is opioid system.

Placebo activation-induced analgesia is suppressed by an opioid μ-receptor antagonist naloxone. In contrast, cholecystokinin receptor antagonist (CCr) proglumide activates placebo-induced opioid hypoalgesia (the placebo effect is suppressed by the CCK-2p agonist pentagastrin).

However, experiments on mice with the injection of cholecystokinin into the rostral ventromedial part of the spinal cord and the subsequent hyperalgesia are associated with a multiple increase in the production of PGE2 (prostaglandin E2) and 5-HT (5-hydroxytryptamine) (suppression of PGE2/5-HT synthesis significantly reduces pain symptoms).

PET studies of the brain also provide evidence of the active participation of the opioid system in placebo analgesia. So in patients receiving an opioid agonist remifentanil, and patients in the placebo group, PET scans revealed activity in the same brain regions, namely the dorsolateral prefrontal cortex (dPFC), anterior cingulate cortex (ACC), insula, and nucleus accumbens (NAcc) (while remifentanil produced significantly greater activity compared to placebo).

In addition, in experiments on mice it was possible to establish that it is the activation of μ receptors that induces placebo analgesia. It would seem that cholecystokinin simply suppresses the function of the opioid system, without playing a role in the formation of the nocebo effect. However, in an experimental mouse model of social stress (“social defeat,” or more simply put, daily bullying over a period of time, most often 10 days), anxiety-induced hyperalgesia was suppressed by administration of a CCK-2p antagonist ( CI-988).

The next system we'll touch on in terms of the placebo and nocebo effects is cannabinoid system. Taking the non-steroidal anti-inflammatory drug (NSAID) ketorolac for 2 days followed by placebo induces analgesia that is not suppressed by the opioid receptor antagonist naloxone, whereas the cannabinoid receptor antagonist (CB-antagonist) does not. rimonabant completely eliminates the placebo effect.

Functional missense gene mutation Pro129Thr, encoding FAAH (fatty acid amido hydrolase), a major enzyme that degrades endogenous cannabinoids, activated placebo analgesia as well as placebo-induced μ-opioid neurotransmission.

The dopaminergic system is also involved in creating the placebo effect. Placebo analgesia is accompanied by an increase in the binding of dopamine to D2/D3 receptors and endogenous opioids to u-receptors, observed in the nucleus accumbens, while inactivation of these receptors is manifested by nocebo hyperalgesia.

Similarly, when a placebo is given to patients with Parkinson's disease, dopamine receptors are simultaneously activated in the ventral (NAcc) and dorsal striatum. Given the stimulation of the NAcc that occurs as a result of placebo administration, it can be assumed that the reward system is involved in creating the placebo effect.

A meta-analysis of brain imaging studies (PET or fMRI) and correlations with placebo analgesia demonstrated the following: when expecting placebo analgesia, there was increased activity in the anterior cingulate gyrus, precentral and lateral prefrontal cortex, and periaqueductal gray. substances, and, conversely, a decrease in activity was observed in the areas of the medial and posterior encircling cortex, superior temporal and precentral gyrus, anterior and posterior insula, cervical and putamen, thalamus and caudate nucleus.

Mechanisms of placebo formation

As mentioned earlier, two processes are involved in the formation of the placebo effect: learning and expectation. Both of these mechanisms rarely do without each other, but sometimes one phenomenon prevails over the other. Training and subsequent instillation of positive/negative expectations can come indirectly through other people, through the media, etc. For example, one form of training is social propaganda.

In hypobaric hypoxia-induced headache, placebo analgesia resulting from social propaganda resembled the effect of aspirin, when nocebo-induced headache activated by social propaganda was accompanied by increased expression of prostaglandins.

Let us consider the above-described effect of such propaganda using the following example. The spread of negative expectations among a separate group leads to a nocebo effect in the form of the formation of a justification for such an expectation, which was demonstrated in a study in which people divided into 2 groups rose to a height of 3.5 thousand m. In the first group (nocebo- group - 36 people) the mechanism of social propaganda was induced, which was manifested by the occurrence of headaches during the rise, the second group was the control group (38 people).

The methodology for setting up this experiment is quite interesting: first, one person was “infected” with the expectation of a severe headache (later it became a trigger), while the experimenters told him that such pain was relieved by aspirin. After this, the person developed a headache, he took aspirin and suppressed it.

The researchers also reported possible headaches to other experimental subjects from the nocebo group, and for more complete information they recommended contacting the first person—the trigger. A week later, the nocebo group and the control group went on a hike to an altitude of 3500 meters above sea level. At altitude, the nocebo group had more headaches, and the levels of prostaglandins, thromboxane and cortisol in saliva were higher than in the control group.

Next, in each group, patients with headache were divided into 3 subgroups: a subgroup that was given aspirin ( aspirin group), the subgroup that was given placebo ( placebo group) and the untreated subgroup ( no treatment group).

What happened in the end?

When comparing levels of prostaglandins, thromboxane and pain severity in response to placebo or aspirin, the following results were obtained:

• In the control group, placebo had almost no effect; aspirin, as expected, reduced the severity of headache;
• In the nocebo group, both aspirin and placebo were shown to be equally effective.

The placebo was effective in the nocebo group, because the resulting pain and increase in prostaglandins were due to the influence of social nocebo propaganda. Both placebo and nocebo can be influenced by environment and social interactions. This is also important to consider when prescribing conventional medications.

The next experiment tested the severity of the formation of postoperative pain syndrome. As can be seen from the study, which was conducted on mice, testing the effectiveness of the placebo effect was not of primary importance.

However, the study revealed that anxiety and lack of sleep in the preoperative period increased the severity of pain several times after surgery, which in the future could lead to chronicity of this pain. A potential role in the development of this effect is attributed to the preoptic adenosinergic A2 receptor system in relation to the SLEEP-PAIN axis.

Regarding chronic pain, a clinical study was conducted on 83 patients with lumbar pain lasting more than 3 months. The criteria for inclusion in the experiment were the following characteristics: age over 18 years, absence of surgical operations on the lumbar spine, absence of severe fibromyalgia, fractures, neoplasms, infections, degeneration of intervertebral discs with the possibility of injury; opioid use less than 6 months before the study was excluded. The study did not include patients with severe mental disorders and paralysis, as well as patients prone to stopping medication on their own.

Pain severity was assessed using three numeric rating scales ranging from 0 to 10: maximum, minimum, and usual pain, as well as a composite primary outcome of total pain score (the average of the three pain scales). The other outcome measure was decreased quality of life associated with low back pain, assessed using the Roland-Morris Questionnaire.

The study randomly selected 97 adults who reported persistent low back pain for 3 months or more, as verified by a board-certified specialist at a hospital. 83 people completed the study. Compared with TAU (drug therapy as usual), OLP (informed placebo administration) resulted in greater pain reduction on each of the three 0-10 point numeric scales and moderate to greater benefit on the combined 0-10 point scale (P 0.001) . OLP also contributed more to the improvement of life function compared to TAU (P, 0.001). The improvement in disability scores was 2.9 (1.7 to 4.0) in the OLP group and 0.0 (−1.1 to 1.2) in the TAU group.

In a follow-up study, TAU participants received placebo pills for 3 additional weeks. After switching to OLP, the TAU group showed significant reductions in both pain (three scale mean 1.5, 0.8-2.3) and dysfunction (3.4, 2.2-4.5).

The effect of suggestion-training is clearly visible: despite the fact that the patients knew about taking placebo, placebo analgesia had a better effect than other analgesics. The placebo effect manifests itself differently when no training technique is applied to the patient.

The first graph shows the result of hidden and open use of the drug. On the second stage - hidden and open withdrawal of diazepam. This demonstrates how the anticipation of anxiety from false drug withdrawal leads to the manifestation of this anxiety and vice versa.

An interesting study in which, to suppress postoperative pain after third molar extraction, patients were given either a hidden intravenous injection of 6-8 mg of morphine or an open intravenous injection of a placebo solution in full view of the patient. The effect of open-label placebo was comparable to that of morphine.

In other words, telling the patient that a painkiller (which is actually a saline solution) is being injected is as effective as injecting 6-8 mg of morphine. This works with a variety of pain relievers such as morphine, buprenorphine, tramadol, ketorolac, and metamizole.

Thus, even for opioid analgesics, the effect of informing the patient is important, forming the effect of his expectation of pain relief. Based on the above studies, it seems that placebo is necessarily a conscious phenomenon. But is this really so?

Some studies demonstrate activation of placebo and nocebo to unconscious stimuli. A strong statement. We will, of course, check it.

In 2014, Karin B. Jensen conducted a study in which 24 subjects (10 women and 14 men) were selected to participate. The study consisted of 2 stages. The first stage consisted of demonstrating 2 male faces, each of which was accompanied by a certain thermal stimulation of the hand (the temperature was calibrated as a “strong pain” and a “weak pain” stimulus).

In the first phase, face #1 was presented with a weak stimulus, while face #2 was presented with a strong stimulus. A total of 50 stimuli were produced - 25 for each face, and so on twice for 10 minutes (to ensure that the stimulus was remembered).

The second stage was distinguished by the addition of a “control” stimulus in the form of face No. 3, as well as an “unconscious” stimulus - the presentation of a certain face for 12 milliseconds, as a result of which the subject was not aware of the appearance of this photograph.

Each photograph was accompanied by the same temperature stimulus, with a temperature intermediate between the strong and weak pain stimuli. 60 stimuli were administered, 20 for each “face,” three times over 10 minutes. During the experiment, subjects were asked to describe the pain they experienced on a scale from 0 to 20, and fMRI was also used to study the activation of brain zones, recording the activity of various brain zones.

The results of the experiment are as follows: the unconscious nocebo was more sensitive to pain than the conscious nocebo, and the unconscious placebo effect was more pronounced than the conscious one, although both differences are not particularly sensitive.

Regarding the fMRI data, the placebo effect was associated with activation of the rACC in both conditions, but in the unconscious placebo effect there was a significant activation of the orbitofrontal cortex (OFC).

During the nocebo effect, the ACC, bilateral insula, thalamus, and brainstem were activated. During unconscious nocebo, more pronounced activation compared to conscious nocebo was observed in the brainstem, thalamus, amygdala and hippocampus. In a study of the unconscious nocebo effect, the level of activation of the right amygdala was positively correlated with the level of pain; no such analogy was observed in the left amygdala.

Thus, neuroimaging studies demonstrate that the limbic system and prefrontal cortex are actively involved in mediating placebo and nocebo effects. Evidence of this will be conditions in which, due to disturbances in the activity of the prefrontal cortex, the placebo effect is not able to be activated.

All the studies we reviewed above have the following disadvantages:

1. Subjectivity;
2. Small selection;
3. Difficulty in everyday practice:

• It is necessary to anticipate the development of the placebo/nocebo effect;
• Limited patient population and types of pathologies, etc.

And yet, placebos and nocebos work!

Editorial: Elena Breslavets

Placebo is a treatment that helps with any disease, but not all. The placebo effect in medicine is generally accepted. Its essence is that if the patient is confident in the effectiveness of a particular drug or procedure, then he can get the expected effect.

Moreover, a positive result can be achieved even in the case of fictitious treatment. If you think that three tablets will help you better than two, or you are sure that capsules are more effective than tablets, then there is a high probability of finding confirmation of this from your own experience. And if you believe that expensive original drugs are better than cheap generics, then most likely your money will be well spent.

But placebo has an antipode - nocebo. Nocebo is a phenomenon much less studied than placebo and is much less common in clinical practice. The term nocebo comes from the Latin noceo - to harm. These terms denote something that has no real effect, but causes any negative reactions in a person, even to the point of his death.

There are many examples of nocebo action. Deaths have been reported in patients who were misdiagnosed as fatal. Unfortunately, the error was discovered only at autopsy. Difficulties in studying the nocebo effect arise from ethical requirements that prohibit interventions that could cause harm to subjects. But still, scientists are studying this phenomenon. Thus, in one study on volunteers, the connection between mobile phone use and headaches was studied. Some of the subjects complained of headaches even when they were given an imitation phone instead of a telephone (without their knowledge).

Drugs can also play a nocebo role. Thus, patients sometimes report unexpected and uncharacteristic side effects for a given drug that cannot be explained by the mechanism of action of the drug. There are several factors associated with an increase in the number of side effects. These include: the patient's expectation of certain adverse reactions at the beginning of treatment, previous experience of treatment with these drugs and, especially, the patient's personal characteristics.

Despite the lack of knowledge about the physiological basis of nocebo action, some data are still available. Patients anticipating increased pain have been shown to experience increased anxiety. This leads to activation of cholecystokinia and increases pain. This response creates a vicious cycle of anxiety and pain, which may explain the nocebo effect. The dopaminergic and opioid systems also play a role in the development of the placebo or nocebo effect.

The nocebo effect has important implications for clinical practice. It is necessary to determine which patients are at risk of developing a nocebo effect. When communicating with such patients, you should especially carefully choose words and terms so as not to worsen their condition. And with the development of nonspecific side effects, one should keep in mind the possible nocebo effect and take this into account during further treatment.

Placebo and nocebo are two sides of the same coin. Which of them will manifest itself in each specific case depends on the patient’s expectations, i.e., on the prognosis he makes for himself. And the nature of this prognosis largely depends on the doctor’s literacy.

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Nocebo effect – this is a manifestation of a negative reaction in response to negative expectations. That is, this is the opposite effect to the placebo effect. When a person thinks that he is sick with something or does not believe in the effectiveness of medicine, as a result of which, he is not positive expectations and sales. And if the placebo effect can in some cases even determine the effectiveness homeo-pa-ti-ches-kih pre-pa-ra-tov , then the nocebo effect can in some cases manifest itself in a completely miraculous manner. In particular, recently a study was carried out on the influence of knowledge of a person's own genes such special sensations and hor-mo-nal background. As a result, it turned out that knowledge affects sensations and the hormonal background to a greater extent than the mutations themselves.

Recently, in general, genetic tests have become very popular. What has become possible thanks to the development of DNA seq-ve-ni-ro-va-niya technologies. And such tests are carried out not only on em-bri-o-ns, but also on adults. Although so far only em-bri-o-nov tests can be of practical benefit. That with the art-kus-st-ven-nom op-lo-dot-vo-re-niy it is possible to select em-b-ri-o-ns with the most ten-tsi-al-but high IQ. And it may be immoral, but at least it’s useful. But gender tests for adults are not only useless, they are downright harmful. Although, it would seem that knowledge about a woman’s predisposition to this or that disease can help a person speed up your own way.

Impact of DNA tests

The whole problem is that people are ir-ra-tsi-o-nal-ny and emo-tsi-o-nal-ny. Therefore, when a person finds out that he has some kind of genetic disadvantages, then instead of compensating them with his according to him, he, on the contrary, waves his hand at everything, “offends” and believes that “then let everything burn in flames." Of course, not everyone acts like that! But on average, this is exactly the reaction. For example, when people are informed that they have a predisposition to diabetes, then instead of sitting on di-e-tu with di-a-be-those and spend time with-from-vet-s-t-vu-yu-shay fi-zi-ches-koy active-nos-ti , they either did not change their way of life, or, on the contrary, they even lost it.

And you yourself could have observed such a unique nocebo effect. For example, in the gym. When people think that they have a “bad gene,” and instead of putting in more effort, they, for example, ro-tiv, try less. And, es-test-ven-but, that the result-ta-you are dreaming even more strongly. Moreover, this belief of theirs in their own inequities can have a more powerful effect on their results than themselves the fact of the presence of additional non-dos-tats. And even if in fact there are no such inconsistencies. Because the or-ga-ism of a person, who believes that he has insufficient-tat-ki, responds to this faith more powerfully than the or-ga- the bottom of a person, in fact, about them.

Genetic nocebo effect

On December 10, 2018, the journal Nature published a study of the influence of knowledge about the presence of mutations in genes on sensations and hormones. ny background man-lo-ve-ka. It was blind. That is, neither the researchers nor the researchers knew the actual results of their DNA tests. But is-the-trace-to-be-to-be-to-be-to-be-to-have-to-have-to-have-to-have or from-to-be-with- t-vu-ut op-re-de-linen mutations. In the re-zul-ta-those of what follow the re-ac-tion of is-py-tu-e-my. In total there are 2 ex-pe-ri-men-ta. In the first, we test-ti-ro-va-li on the treadmill, and in the second, we test-ti-ro-va-li at the table. After which, in the first ex-pe-ri-men, you try to evaluate the feeling of being tired, and in the second, the feeling of hunger. In addition, in the second case, the horizontal background was also measured.

Naturally, before reporting the results of their genetic tests, they went through the first stages of -pe-ri-men-tov. After which you appreciate the feeling of tiredness and hunger. And they also forgot about the mountainous background. Then they ot-dy-ha-li, they were informed about the results of the DNA tests and asked to undergo ex-per-ri-men again. As it turns out, people who are aware that they have a genetic predilection for women -she-noy tired-la-e-mo-ti, na-chi-na-whether you get tired faster on the treadmill. Moreover, the influence of their knowledge was more powerful than the presence of an actual mutation. That is, people who simply believed that they had such a mutation learned it faster than people who had it.

But in the second experiment, no additional nocebo effect was observed. But the placebo effect was observed. Thus, people who have reported that they do not have a pre-disposition to re-e-da-yes, are communicated faster than people who believed that they had such a mutation. Moreover, this belief even influenced the hor-monal background of the is-py-tu-e-my. That is, they not only subjectively evaluate their feeling of hunger, but also their organism is act-s-t-vi-tel-but less pro-in-ci-ro - I wanted to eat them. And, again, the influence of belief in the presence or absence of mutations had a greater influence than the factual data -nye.

Dr. Lissa Rankin at TEDx, It's never too late to calmly and carefully listen/watch/read in this text now. It describes, from a scientific point of view, the mechanisms of miraculous self-healing from any disease (including cancer at the last stage) or sudden death from the “evil eye”.

Zozhnik provides the text of this important speech by Lissa (with subheadings, editing, links and pictures).

Can consciousness heal the body? And if so, is there evidence to convince skeptical doctors like me? These questions have driven my research in recent years. And I made the discovery that the scientific community, the medical establishment over the last 50 years have proven that consciousness can heal the body. This is called the "placebo effect."

The Science of Self-Healing

We've been trying to outwit him for decades. The placebo effect is a thorn in the side of medical practice. This is the unpleasant truth that stands between implementation
new types of treatment, new surgical methods in medical practice.

But I think this is rather good news because it is ironclad proof that the body contains internal repair mechanisms that allow the unthinkable to happen to the body.

If you find this surprising and find it hard to believe in self-healing,
you should check out The Spontaneous Remission Project, a database compiled by the Institute of Noetic Sciences. These are more than 3,500 cases described in the medical literature of patients who recovered from so-called “incurable” diseases.

You will be shocked if you look at this database. It contains everything: the fourth stage of cancer disappeared without treatment, HIV-positive patients became HIV-negative, heart and kidney failure, diabetes, hypertension, thyroid diseases, autoimmune diseases disappeared.

The case of “Mr. Wright”

This is a famous case, studied in 1957, which you may have come across on the Russian-language Internet. The patient, the so-called “Mr. Wright” ( Judging by the sources, the patient’s name is provisional, - approx. Zozhnik) was an advanced form of lymphosarcoma. The patient was not doing very well, he had little time left: tumors the size of oranges in the armpits, on the neck, in the chest and abdominal cavities. His liver and spleen were enlarged, his lungs took on 2 liters of cloudy fluid every day and had to be drained so he could breathe.

But Mr. Wright did not lose hope. He learned about the wonderful drug Krebiozen and begged his doctor: “Please give me Krebiozen and everything will be fine.”
His attending physician, Dr. West, could not do this due to the novelty and insufficient study of the new drug. But Mr. Wright was persistent and did not give up, he continued to beg for medicine until the doctor agreed to prescribe Krebiozen.

Demonstration for the speedy distribution of a new wonderful cancer drug - Krebiozen, which turned out to be a dummy after testing.

He scheduled the dose for Friday of the following week. Hoping Mr. Wright doesn't make it to Monday. But by the appointed hour he was on his feet and even walking around the ward. I had to give him medicine.

After 10 days, Wright's tumors had shrunk to half their previous size. A couple more weeks passed after I started taking Krebiozen and they completely disappeared. Wright danced with joy like crazy and believed that Krebiozen was a miracle drug that cured him!

This went on for two whole months until a full medical report on Krebiozen was released, which stated that the therapeutic effect of this drug had not been proven. Mr. Wright became depressed and the cancer returned.

Dr. West decided to cheat and explained to his patient: “That Krebiozen was not purified well enough. It was of poor quality. But now we have ultra-pure, concentrated Krebiozen. And that’s what we need!”

Wright was then given a placebo injection. And his tumors disappeared again, and the fluid from his lungs went away. The patient began to have fun again. All 2 months until the Medical Association of America ruined everything by releasing a national report that definitely proved that Krebiozen was useless.

Two days after Wright heard the news, he died. He died despite the fact that a week before his death he was flying his own light aircraft!

"Nocebo" - the opposite of placebo

Here is another case known to medicine that looks like a fairy tale. Three girls were born. The birth was attended by a midwife on Friday the 13th and she began to claim that all children born on that day were susceptible to spoilage. “The first one,” she said, “will die before her 16th birthday. The second is up to 21 years old. The third is up to 23 years old.”

And, as it turned out later, the first girl died the day before her 16th birthday, the second - before she turned 21. And the third, knowing what happened to the previous two, the day before her 23rd birthday, ended up in the hospital with hyperventilation syndrome and asked the doctors: “I’ll survive, right?” She died that night.

These two cases from the medical literature are excellent examples of the placebo effect and its opposite, nocebo.

When Mr. Wright was cured by distilled water, this is a good example of the placebo effect. You are offered inert therapy - and somehow it works, although no one can explain it.

The nocebo effect is the opposite. These three girls who were “jinxed” are a prime example of this. When the mind believes that something bad can happen, it becomes a reality.

Measurable Placebo Effects

Medical publications, journals, the New England Journal of Medicine, the Journal of the Medical Association of America are all full of evidence of the placebo effect.

When people are told they are being given an effective drug, but instead are given saline injections or regular sugar pills, this is often even more effective than actual surgery. In 18-80% of cases people recover!

And it's not just that they think they feel better. They actually feel better and it's measurable. With modern instruments, we can observe what happens in the bodies of patients who take a placebo. Their ulcers heal, symptoms of intestinal inflammation decrease, bronchial tubes expand, and the cells begin to look different under a microscope. It is easy to confirm that this is happening.

I love Rogaine's research. There's a group of bald guys, you give them a placebo and their hair starts growing.

Or the opposite effect. You give them a placebo, call it chemotherapy, and people start vomiting and their hair falls out!

The doctor and health workers are also a placebo (or nocebo)

But is it really just the power of positive thinking that produces these results? No, says Harvard scientist Ted Kaptchuk. He believes that the most important thing is that the care and concern provided by a health worker is more influential than positive thinking. Some studies say that the doctor is actually a placebo.

Ted Kaptchuk observed patients who received placebo as a therapeutic therapy. And he told them: “This is a placebo and there is nothing in it, no active substance.” But they still recovered. The majority, as Kaptchuk admitted, thanks to care and care, they wanted and they did something and felt that they were cared for.

The body has a natural internal healing mechanism, but science shows that it requires the care and attention of a health professional, such as a healer, to facilitate the process.

It is not easy to cope with an illness alone and it makes a big difference when someone supports that confidence. But The problem is that the doctor can be either a placebo or a nocebo.

What do patients need from us healthcare workers? They need us to be a force of healing, not fear or pessimism. Therefore, when the doctor says: “You have an incurable disease, you are doomed to take these drugs for the rest of your life.” Or “You have cancer. You have 5 years left to live." It's like that midwife telling those three newborns that they were jinxed.

As doctors, we want to be realistic, you know? When we give people information that we think they should know, but in reality we can do harm.

Instead, doctors should be like Dr. West and give distilled water. "Mr. Wright, I promise this will help you."

Health Pyramid

What do placebo and nocebo effects in their pure form indicate? Can we do anything without clinical trials?

My hypothesis says that to heal ourselves, to be optimally healthy, we need more than just a good diet, regular exercise, getting enough sleep, taking vitamins, following doctor's orders. This is all good, critical and important.

But I also became convinced that we need healthy relationships, a healthy work environment and creative life, a healthy spiritual life, a healthy sex life, financial health, the environment. Finally, we need a healthy mind.

I wanted to prove this so badly that I found literature and extensive data that proved that all of this was significant and changed my mind. I've collected them in my upcoming book, Mind Over Medicine: Scientists Prove You Heal Yourself.
I want to introduce you to the key aspects of this. As you can see from this entire health pyramid, all edges are built on a foundation that I called the inner wick.

What is important to me is the authentic part of you that knows what is true for you. This desire to bring the truth to you may not apply to your life, and the stones in the pyramid of your health may not be balanced.

I placed body and physical health at the top of the pyramid. Because it is the most fragile, the most shaky, the most easily destroyed if something goes wrong in your life. From medical data, I have discovered that relationships matter. People with strong social networks have half the risk of heart disease compared to those who are lonely.

Married couples are twice as likely to live longer than those who are not married. Healing your loneliness is the most important preventative measure you can take for your body. This is more effective than quitting smoking or doing exercises.

Spiritual Life Matters. Churchgoers live an average of 14 years longer.

Work matters. You can work yourself to death. In Japan it is called karoshi. Death from overwork at work. Survivors of karoshi can file a claim for damages. And not only in Japan, this happens very often in the USA, but we do not receive compensation for it. According to a study, people who don't take vacations are 3 times more likely to suffer from heart disease.

Happy people live 7-10 years longer than the unhappy ones, and the optimist is 77% less likely to have heart disease than the optimist.

How it works?

What happens in the brain that changes the body? This is what amazes me. I discovered that the brain communicates with the cells of the body through hormones and neurotransmitters. For example, the brain identifies negative thoughts and beliefs as a threat.

You are lonely or pessimistic, something is wrong at work, a problematic relationship and the amygdala screams: “Threat! Threat!" The hypothalamus turns on, then the pituitary gland, which communicates with the adrenal glands, which begin to splash out stress hormones - cortisol, norepinephrine, adrenaline. What comes into play is what Walter Kennett of Harvard calls the stress reaction. Which turns on the sympathetic nervous system, putting you in a "fight or flight" state, which is protective if you're running from a mountain lion.
But in everyday life, in the event of a threat, that quick stress reaction arises, which should be turned off when the danger has passed. But in our case this does not happen.

Fortunately, there is a counterbalance to the relaxation mechanism described by Herbert Benson of Harvard University. And when the direction changes, the stress response turns off and the parasympathetic nervous system turns on, healing hormones such as oxytocin, dopamine, nitric oxide, endorphins, flood the body and cleanse every cell.

Most surprisingly, the natural self-healing mechanism is activated only when the nervous system is relaxed. Therefore, in a stressful situation, all self-defense mechanisms are not activated. The body is too busy trying to fight or flee rather than heal.

When you think about it, you ask yourself: How can I change the balance of my body?

One report shows that on average we experience more than 50 stressful situations every day. If you're lonely, depressed, unhappy in your job, or have a bad relationship with your partner, the number at least doubles.

Therefore, the relaxation response is believed by researchers to explain the placebo effect. So when you take a new wonder drug, you don't know whether it's a placebo or not. The tablet triggers a relaxation mechanism; the combination of a positive attitude and proper care from a healthcare professional relaxes the nervous system.

And then that natural self-healing mechanism turns on. Luckily, you don't have to participate in a clinical trial to enable relaxation. There are many simple and enjoyable ways to kick-start your relaxation mechanism. And this is proven by research.

• meditate,
• express yourself creatively,
• give a massage,
• do yoga or tai chi,
• go out for a walk with friends,
• do what you love,
• sex,
• you can laugh,
• do exercises,
• play with animals.

I ask you to consider your own health pyramid. What bricks are not balanced in it? Each of the bricks can be a factor creating a stressful situation or relaxation. How to increase the amount of relaxation in your body?

And most importantly: what does your body need to heal itself? What prescription do you need? Do you have the courage to admit the truth that your inner source already knows?

I think our healthcare system is in terrible shape, mainly because we have forgotten the body's ability to heal. The medical establishment is too arrogant. We are used to thinking that with all modern technology, all the knowledge of past centuries, we have mastered nature and refuse to think that nature can sometimes be better than our medicine.

We must take responsibility for our body, your consciousness has enormous power, interact with the body and heal it. It all starts with you.
Be the love you want to see in healthcare.

And I believe miracles will happen. As soon as you do this, oxytocin and dopamine are released and self-healing begins.