Placebo and nocebo, phenomena as different as fire and water, in which, despite the use of an inert substance, the consequences of its administration – biochemical, physiological, behavioral, emotional and cognitive – are very real. So what is the strength in the doctor’s words?
- Medicine proves that sometimes it’s better to be deceived – a neutral substance, when used with the right attitude, can be as effective as some therapies, and is much cheaper and devoid of side effects
- The placebo effect is enhanced when the inert substance is administered by a doctor, not a nurse
- The nocebo effect occurs when harmful symptoms develop during sham treatment
Placebo (Latin I will like it) is understood as a substance or pharmacologically neutral substance that has no proven physiological effect on the patient’s health and the disease it is intended to remedy, and is administered to the patient with the suggestion that it is an active agent. By placebo we usually mean a biologically inactive substance, but the definition and effect of a placebo go beyond counterfeit drug therapy.
Placebo is also a sham surgery, alleged stimulation with a magnetic field, current and elements accompanying the treatment situation: the hospital itself, the characteristic clothing of the medical staff, medical equipment present in the room and used in the presence of the patient, especially if it seems modern and highly specialized. The effect of these nonspecific psychological and biological factors is called the placebo effect. It hides the element of satisfying essential needs, meeting expectations, and therefore the essence of what is expected from treatment: bringing relief, reducing pain, suffering and fear. As Hippocrates used to say, “the best medicine is the doctor himself”.
Medicine proves that sometimes it’s better to be deceived – a neutral substance, when used with the right attitude, can be as effective as some therapies, and is much cheaper and devoid of side effects. It is also not worth being negative about the changes in treatment proposed by the doctor, because it may turn out that the lack of effectiveness of the therapy does not depend on the active substance, which shows how effective the medicine is is a positive attitude and the will to live.
The mechanisms of the placebo effect – both psychological and physiological, can be understood primarily in behavioral-cognitive and social terms. Some of the placebo effects can be explained by classical conditioning. Studies in dogs given morphine with a conditional stimulus show that after some time the conditional stimulus alone leads to a typical response prior to injection. Similarly, in humans, the reaction of, for example, reduction of pain after taking a drug in a tablet causes a feeling of relief immediately after taking the drug.
The importance of the cognitive variables: perceptions, beliefs and expectations should also be taken into account. Man tends to be consistent between his beliefs and his behavior and experiences. Expectations are shaped on the basis of our previous experiences, experiences and patterns. Since there is a common belief that injectable drugs are “more important” and more effective, the placebo effect associated with this form of drug will be more pronounced than for drops or tablets. The color of the latter is also of great importance. If they are pink or white, they will have a stronger effect, e.g. in cardiovascular diseases. While green and blue in insomnia and anxiety disorders. Tablet size is also important. Even if the content of the active substance in the drug is small, the tablets should be of medium size. The placebo effect is enhanced when the inert substance is administered by a doctor, not a nurse.
Placebo studies have shown that it causes not only specific physiological changes as expected (e.g., toothache relief, not other pain relief), but also causes general changes described in terms of psycho-neuro-immunology.
Placebo is not only a psychological phenomenon, because it is also a physiological reality with clinical consequences, but also addiction (tendency to increase doses). This observation suggested that perhaps one of the mechanisms of placebo action is the release of endorphins. Levin’s study of the analgesic effect of placebo in dental procedures confirmed that administration of naloxone abolished the analgesic effect of placebo in responders. This experience demonstrates the importance of endorphins in the neurophysiological reward mechanism.
In turn, negative suggestions can cause disease symptoms. The nocebo effect occurs when harmful symptoms develop during sham treatment as a result of negative expectations. Strictly speaking, nocebo occurs when the patient’s condition worsens as a result of the administration of a neutral or mock agent. The most common effect of nocebo is penicillin allergy. After its administration, about 10 percent. of patients experience negative symptoms. As a result of the research, it was shown that 97 percent. cases of allergy to this antibiotic are the result of the nocebo phenomenon.
In another experiment, fumes that, according to the doctors, were supposed to contain allergen or chemicals, were blown into the room of patients with diagnosed asthma. Almost half of the respondents developed symptoms associated with an asthma attack. In fact, brine vapors were introduced into the room. In another study on a fibromyalgia drug, the number of participants suffering from the nocebo effect was so large that the experiment had to be discontinued due to the nuisance side effects of the therapy. For the same reason, about 26 percent. patients discontinue use of a dummy substance that has been presented to them as a statin. A flagship example of the nocebo effect is lactose intolerance. In an experiment by Italian gastroenterologists, people diagnosed with lactose intolerance were given a tablet with a verbally low content in order to investigate the effect of lactose on the motor function of the intestines. In fact, the participants were given tableted glucose. Despite this, 44 percent. people complained of digestive system ailments.
The nocebo effect can also be seen when a person actually uses drug therapy. The discussed phenomenon may reveal itself through unintentionally negative suggestions from medical personnel, e.g. when they inform the patient about possible complications of the treatment undertaken. It is assumed that some of the side effects of drugs may be attributed to the nocebo effect. A group of men was given finasteride to treat benign prostatic hyperplasia. Half of the patients were told the drug could cause erectile dysfunction, while the other half were unaware of it. In the first group, as much as 44 percent. participants reported that they experienced erectile dysfunction, while in the latter the percentage was less than 15%.
The result of the study of remifentanil, an opioid drug 500 times more potent than morphine, used in cancer pain relief patients is truly striking. Patients were given the medicine with a warning that it could make their pain worse for the first 15 minutes. As a result of the announcements, about 30 percent. patients reported complaints about which the doctor had warned.
In “Deutsches Ärzteblatt International”, Winfried Häuser from the Technical University of Munich and his colleagues discuss the underlying neurobiological mechanisms of nocebo. They indicate that the mechanism of this phenomenon is – as in the case of placebo – classical conditioning and a response to induced expectations. It is assumed that in the case of the nocebo effect, we are dealing with the activation of the body’s defensive reserves for the stress and threat induced by the word. Harvard psychiatrist Dr. Arthur Barsky emphasizes that “when we are sick, we pay much more attention to our body and tend to attribute pre-existing symptoms to the disease or treatment.”
Researchers from the University Hospital of Grenoble indicate that the nocebo effect may be modulated by cholecystokinin (CCK). There is evidence that CCK causes hyperalgesia, turning anxiety into pain. Nocebo effects through the negative expectation model induce and mobilize the HPA axis. The concentration of ACTH and cortisol increases. Nocebo hyperalgesia and higher HPA axis activity can be antagonized with diazepam, which supports the hypothesis that anxiety plays a major role in these processes.
The effects of placebo and nocebo are associated with opposite responses of the dopaminergic system and the endogenous neurotransmission of opioids in different regions of the brain. Scott et al. (2008) have shown that high placebo responses are associated with greater dopaminergic and opioid activity in the nucleus accumbens (decreased μ-receptor binding potential), while nocebo responses are associated with dopamine inactivation. These processes are activated by opposite expectations, analgesia or hyperalgesia, respectively. Oral suggestions for a positive result (pain reduction) activate endogenous opioids, while suggestions for a negative result (increase pain) activate CCK-A and / or CCK-B receptors.
Nocebo affects our well-being, which we translate directly into our health. If we know that the suggestions may lead to the projection of side effects, should we inform patients about the possible side effects of the proposed therapy? According to Zsuzsanna Jakab, regional director for Europe from the World Health Organization, the patient is an expert who has valuable therapeutic experience and his activity in the decision-making process is a necessity. Doctors face the ethical problem of choosing between the obligation to inform the patient about the possible side effects of treatment and the obligation to minimize the risk of medical intervention and the appearance of the nocebo effect.
The fall of authority became fertile soil for the growth of the idea of charlatanism and false prophets of medicine. If we decide not to inform patients about the side effects of drugs, for the patient’s sincere well-being, and this fact becomes apparent, we may not be able to reliably explain our noble motives. Repeating Fr. Jan Kaczorowski: “The doctor is the patient’s partner. A properly informed patient will not question your diagnosis.
Source: “Służba Zdrowia” 7-8 / 2019