Placebo and Nocebo effects: when the mind influences the effects of drugs

By Cristiano Antonino On Nov 16, 2021

Placebo and nocebo are two sides of the same coin and represent a complex phenomenon, not only neurobiological but also psychological, in which neurophysiological and behavioural changes occur following the administration of a therapy

The term nocebo (from the Latin nocere: to harm, to damage) was first used in the literature by Walter Kennedy in 1961.

The placebo effect, on the other hand, has a much longer history: it was originally named in health care in 1772 by the physician William Cullen, who used the word placebo (from the Latin verb translating as: ‘I will please’) to refer to a substance administered to patients with the aim of modulating their symptoms rather than interfering with the disease process.

In 1964, it was shown that the doctor-patient relationship can positively influence the outcome of a treatment; the same applies to the outcome of a positive psychosocial context that is able to positively influence the patient’s brain.

THE NOCEBO EFFECT

It is important to differentiate the nocebo effect from the nocebo response.

The former refers to the (negative) psychosocial context in which the person is placed, the treatment and the neurobiological basis underlying the effect. The nocebo response, on the other hand, refers to non-specific factors (including stress and physiological conditions) which, however, may contribute to inducing the worsening of a condition.

Factors influencing the development of the nocebo effect include:

expectations of the treatment effect, which can be created by verbal suggestions, learning, observation of others and the complexity of the doctor-patient relationship. For example: if it is always the same doctor, in the same outpatient clinic, who administers the same tablet, expectations of the treatment will be stronger and the effects will therefore be more pronounced;
informing patients about stopping a treatment can lead to the development of side effects, even though the treatment is still ongoing;
the experience we have and the importance we attach to the context in which we find ourselves are very important stimuli which are carefully processed by our brain.

Several studies have tried to understand the influence that personality traits can have on the nocebo effect and whether they can, in any way, be predictive of the magnitude of this effect.

The results showed that the more anxious and characterised by excessive fear and shyness people were, the stronger were their beliefs and expectations regarding the negative effects of treatment.

Similarly, the less optimistic, determined and ambitious people were, the more they tended to have strong expectations about the negative effects of the treatment given.

A study published in Science by A. Tinnermann and colleagues from the University Medical Centre Hamburg-Eppendorf, Germany, demonstrated a curious phenomenon related to the nocebo effect: it is significantly more frequent when the subject is convinced that the fake drug is very expensive.

Other research has found that the patient’s negative expectations evoked by the clinician’s verbal suggestions are usually sufficiently ‘powerful’ to create a greater nocebo effect than the placebo effect.

In contrast to the placebo effect, therefore, the nocebo effect is based on a lack of trust in drugs and medical staff.

Nocebo responses can also result from past negative experiences associated with certain treatments.

THE PLACEBO EFFECT

The placebo effect, on the other hand, comprises the set of psychological and biological changes due to non-pharmacological factors that occur in the healing process.

For this reason, some experts who have studied this mechanism consider it to be a phenomenon attributable to suggestion and autosuggestion.

At present, the placebo effect in medicine is only used for research purposes, and therefore not as an actual therapy

Medical-scientific studies have shown that the placebo effect in this particular field of application acts mainly on symptoms rather than pathology. Benefits are also often dictated by experience.

A drug that has already been tried, with good results, is more effective than a new one. As is the case with third-party observation: seeing someone achieve a state of wellbeing by taking a drug helps to develop an even more effective response to the drug once we have taken it.

A 2010 review of 202 case studies showed that the placebo effect is curative in treating symptoms of asthma, pain, nausea and phobias.

The placebo effect has far less obvious outcomes on insomnia, dementia, depression, obesity and hypertension. Placebos, in fact, act on the way the patient experiences symptoms, not on the causes of the symptoms.

It is not yet known whether the placebo effect can be induced.

Some research carried out on patients who were aware that they were taking a placebo treatment has produced good results in cases of allergic rhinitis, back pain, irritable bowel syndrome, depression and attention deficit hyperactivity disorder.

Certainly it has been found that a good doctor-patient relationship and good communication by clinicians can have a great positive impact on therapy and the beneficial response to it.

Article written by Dr Letizia Ciabattoni