All You Need to Know About the Nocebo Effect

You're most likely familiar with the placebo effect, but do you know what the nocebo effect is? It can be understood just as the opposite, but it has its own characteristics.

Written and verified by la psicóloga Leticia Aguilar Iborra.

Last update: 25 April, 2023

Although we’re familiar with the characteristic phenomenon of the placebo effect, the nocebo effect is also related to the administration of treatment and the possible effects, in this case adverse effects.

The nocebo effect, in general terms, is similar to the placebo effect in that the adverse effects of any substance, medication, or some other type of treatment appear subjectively.

This effect results from a combination of psychological and neurological effects. Although their effects are subjective, they can be a hindrance to research and clinical results.

In this sense, in the this effect, the beliefs and expectations of individuals influence the results of the treatment.

Approach to the definition of the nocebo effect

The term nocebo comes from the Latin, which could be translated as “to hurt”. Walter. P. Kennedy was the pioneer in referring to this phenomenon in 1961 to refer to the harmful effects administered after a placebo treatment.

In this sense, the nocebo effect refers to the appearance of adverse effects after the administration of any type of treatment. These adverse effects appear subjectively.

It’s common for the this effect to impair some of the research for treatment purposes, as it can mediate research outcomes. Therefore, it’s extremely necessary to develop positive framing strategies.

This provides the patient with information about the treatment being administered and possible adverse effects with the aim of not creating negative expectations in the individual that could favor the nocebo effect.

These effects treat most of the non-serious symptoms. They’re independent of dose administration and not attributable to treatment.

What are the causes of its appearance?

The clear mechanisms by which the nocebo effect occurs are still unknown. In some cases, investigating this type of phenomenon may involve ethical and/or legal problems. The latter means that the veracity of the symptoms isn’t raised with the person in question, and they aren’t informed about the possibility of adverse symptoms, if any.

However, some factors are known that may contribute to the nocebo effect to a greater or lesser extent. Among them, the following can be found:

Factors that contribute to its appearance

Psychological mechanisms are the phenomenon of classical conditioning. It occurs due to the relationship of contingencies with discriminative stimuli that facilitate an adapted response, based on the individual’s expectations.

The memory of a negative response to a type of drug, or a vicarious experience of the effects produced by a similar drug or another type of treatment in other people influences the response to the nocebo effect.

In this sense, the recommendation of the treatment, and the clear and concise information on the effects of the treatment is essential in order to prevent the appearance of this phenomenon.

Personality factors also stand out, since some traits can have an impact on the appearance of the nocebo effect. Today it’s known that introversion traits or a tendency to pessimism can influence the appearance of this effect. The same can be said in individuals with worry-prone neurotic traits.

Neurobiological mechanisms seem to be triggered by the anticipatory anxiety response that is triggered by negative suggestions. The activation of cholecystokinin (CCK) receptors and hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis facilitates the response to pain, producing hyperalgesia.

Contextual factors such as the socio-cultural environment and the specialist-patient relationship are other elements of great importance. Clear information, where the positive aspects of the treatment are reflected, warning of the negative ones, can mediate the risk of the appearance of the nocebo effect.

Medical consequences

The medical consequences of the nocebo effect influence the therapeutic and research results, although more research is needed to know specifically the cause of them. However, its influence is unquestionable in the follow-up of treatment prescriptions.

Therefore, therapeutic prescriptions are influenced by the nocebo effect. It has been seen that some pathologies such as Parkinson’s, multiple sclerosis, neuropathic pain, and migraines are affected by the phenomenon of the nocebo effect.

Also, some treatments are more likely to be involved in this phenomenon. This is the case of statins associated with muscle pain, antiepileptics associated with neurological syndromes, or finasteride, associated with erectile dysfunction.

How to prevent such an effect?

Clear and concise information from professionals is essential in order to reduce the risk of the nocebo effect. Information that isn’t misleading, but at the same time reassuring.

Positive framing usually focuses attention on the benefits of treatment in order to prevent negative expectations about it that have already arisen in the person.

The latter includes searching for treatment and its effects on the internet, false news in the media, observing the effects of treatment on other people, etc.

In other words, a fundamental role is one that is related to the relationship with the professional and the latter’s abilities to inform about the treatment. Although one of the causes of the appearance of the placebo effect is related to the alliance between the professional and the applicant, the nocebo effect is also related to the relationship between them.

Other strategies can be contextualized informed consent and non-information, depending on what the individual wants to know. There’s also the possibility of speaking clearly to patients about the nocebo effect to create awareness of the particularities that may arise during the treatment process.

However, the appearance of certain symptoms is usually inevitable. Emphasis should be placed on a person’s ability to correctly approach mild symptoms and letting them know that intolerance is a problem that can be resolved by changes in treatment.