Nocebo effect: what it is and how it affects people

The placebo effect is a scientific concept of enormous popularity that, perhaps because it is a tremendously curious phenomenon, has become part of the colloquial language. For this reason, many people have an approximate view of what it is and what its scope is.

The placebo describes a positive effect on the organism after the use of a substance whose chemical properties are really harmless, having become known in particular for its presentation as sugar tablets “disguised” as a real drug.

Accumulated evidence suggests that the beliefs and expectations of the person may play a fundamental role for this purpose . In this sense, it is understood that the benefit is associated with internal variables whose analysis is essential to understand the individual response to the use of any drug or therapeutic procedure (regardless of its objective impact on the body).

Like many other things in the field of science, there is also an antagonist for the placebo effect: the nocebo effect . This article will deal precisely with him, highlighting the nature of a less known but equally interesting reality.

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The nocebo effect

The term nocebo comes from Latin. Its form uses a verbal decline in the future for the verb “nocere”, and its literal translation could be “(I) will hurt”. It is, therefore, a phenomenon opposite to placebo. This effect does not refer to any damage that may occur after the consumption of a substance that actually lacks “properties” by which to explain it, and must resort to hypotheses that contemplate the contribution of subjective aspects. Such damages are often referred to as “harmful”, “undesirable” or even “dangerous”.

Its description was much later than that of the placebo, the original references being found in texts of the 70s, although its definitive conceptual delimitation would have to wait until the first years of the 80s. The pioneering experiments on the issue made use of dummy electrical currents to induce supposed “headaches” . In this case, the researchers provided false information to the subjects in a deliberate manner, making them believe that they would feel such a symptom after its application. Although no discharge was ever administered, almost all participants reported having a headache (to some degree) after the trial.

Theoretical models to explain it resort to the role of expectations, as in the case of placebo, but also to classical conditioning and personality variables. The truth is that discovering its nature is important, because sometimes it can undermine the way in which a person adheres to pharmacological treatments that could lead to a frank improvement in their state of health. For this reason, there have been numerous research projects that have been articulated, during the last decade, to better understand it.

In general, we know that up to 19% of people indicate negative side effects derived from using a substance whose chemistry cannot explain them in any way. These are sometimes legal drugs, for which no consequences or damages have been described in the direction indicated, but that the person expressly perceives (sometimes due to past experiences or incorrect “ideas” related to its functioning in the organism). The effect is more common among women (30%) than in men (19%).

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Why happens?

The exact mechanisms by which the nocebo effect concurs are still largely unknown , because their study often involves some kind of ethical or moral dilemma. This is because it would mean lying to the subject about what is administered to him, and in particular making him believe that he will voluntarily expose himself to a dangerous or harmful experimental condition. Because it is necessary for the person to believe in this effect, it would imply the acceptance of self-injurious conditions that escape the deontological codes of the research activity.

However, today there are at least four variables involved in the appearance of the nocebo effect: personal expectations, classical conditioning, personality dimensions and life experience. In this section we will delve into all of them.

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1. Expectation

The value of expectations is essential for the nocebo effect, so that what the subject expects to experience ends up imposing itself in reality as a tangible result on his organs and tissues. That is why in the study of this phenomenon it is essential to offer the person information about the “symptom” that is desired to arise , being this false (in the sense that the substance or procedure lacks any effect on its body), but used with an explicit intent to convince the subject to the contrary. It has been contrasted, in particular, with allergic responses (pain).

With this, and above all by resorting to an authority figure (the researcher), a solid expectation would be formed with the power to generate the suggested negative effects. For example, it is known that beliefs about the emetic effect of chemotherapy (ability to cause nausea or vomiting) are proportionally related to the occurrence of this unpleasant secondaryness.

2. Classic conditioning

The classical conditioning has received a lot of credit as one of the procedures on which the possible development of a nocebo effect is based. In this particular case, it would be an association (by contingency and repetition) of an unconditioned stimulus and a neutral stimulus, the first of which has the ability to elicit a response on the organism (innate). Thus, through repeated exposure to situations in which both occur at the same time, the originally neutral stimulus would acquire the property of a conditioned one . This means that it would generate effects similar to those caused by the original unconditioned stimulus.

A simple example of this type of nocebo was found in a job in which a lemon-flavored drink was offered to a group of people at the same time they received a dose of chemotherapy.

The repeated presentation of this sequence meant that finally the lemon soda (neutral stimulus) was associated with the side effect (nausea) of such treatment (unconditioned stimulus), so that with its isolated consumption the vomiting response occurred. That is, the lemon would generate this unpleasant sensation in the absence of treatment, thus becoming a conditioned stimulus. With this process, a nocebo effect for safe drinks would be acquired.

3. Personality factors

It is known that some personality traits can contribute substantially to the appearance of the nocebo effect . Therefore, they would be tacit elements of mediation between what was previously described (the expectation and the classical conditioning) and its occurrence. With regard to such dimensions, it is now known that pessimistic people (that is, who draw grim expectations on a recurring basis) are more likely to suffer the nocebo effect. In the same way, and perhaps in direct consequence, they do not refer the placebo or its benefits in an equivalent way to those who are optimistic (but much less).

Likewise, type A personality (which refers to a recurring feeling of urgency and competitiveness as an elementary variable in interpersonal relationships) is also associated with a higher risk of nocebo effect, at the time when compared to B (much more “balanced” in time management and social life). The same can be said about neuroticism (tendency to worry and experience negative emotions). Thus, it is concluded that pessimism, neuroticism and attitudes that underline competitiveness are important to understand the phenomenon.

4. Personal experiences

Finally, a fourth explanatory factor is found in previous life experiences. Having witnessed how someone suffered the adverse effects of a drug, or built the forecast that they will occur after acquiring inaccurate knowledge about how they work in the body, is a risk factor associated with learning. All this can be accentuated in the assumption that the original vicar model , from which the expectation was articulated, was someone to whom an emotional bond joins us.

Adverse experiences regarding the health system, as a whole, also precipitate the nocebo effect (since they shape the belief that these professionals are incompetent or that they use invalid judgments). In the event that the treatment is carried out during a forced admission, against the explicit will of the person to whom it is administered, the problem is also aggravated in a remarkable way. This last modality is currently a reason for intense controversy, and should only be applied in the event that a potential risk is suspected for the person or for third parties.

How can it be addressed?

To avoid the appearance of the undesirable nocebo effect, it is essential to influence the variables susceptible to it, such as the person’s expectations regarding the drug or the interaction that occurs in the therapy space. One of the general recommendations is to give the appropriate information and to do it in a realistic way, emphasizing the closest possible balance to the benefits and harms that all medicines have. This is relevant in all intervention contexts, but more so in those that are particularly critical for the expectations that accompany them (for example, chemotherapy, where there are many preconceived ideas about its effects).

It is important to offer information in the most direct and truthful way possible, promoting that the person can actively participate in the treatment they will receive , and that uncertainty regarding it is minimized as much as possible. In this way it is achieved that the subject actively collaborates in his process towards recovery or improvement, and a quality therapeutic link is stimulated. This form of relationship has been shown to reduce the risk of nocebo effect, and is also erected as the way by which to increase the person’s satisfaction with the care received.

In short, the objective of the professional should focus on the contextualization of the benefits and the secondary effects of the compound to be used, in the detection and correction of erroneous preconceived ideas, in the search for active collaboration during the process of making decisions, in the adequate adjustment of expectations and in the construction of a human contact with the person receiving care. All this will contribute to the reduction of the nocebo effect and the proportional increase in therapeutic adherence.


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