The lessebo effect: what is it and how does it affect research?

A curious phenomenon that appears in research on the effectiveness of treatments.

In clinical trials with a randomized control group, it is appropriate to measure to what extent the belief of receiving the experimental treatment influences the degree of improvement reported by the volunteers.

The placebo effect is widely known in research and can be defined as the improvement perceived by participants who believe they have received the effective treatment, even though this is not the case.

However, the placebo effect is not the only effect that can occur in this type of trial. The lessebo effect, along with the nocebo effect, is also a product of suggestion.. Next we will see what the lessebo effect is, in addition to relating it to the other two.

The lessebo effect and relationship to research.

In science, when a new clinical intervention is created, whether it is a drug, a new type of therapy or any new treatment, it is necessary, first of all, to test whether it really works. To do this, it is common for clinical trials to be conducted, which are going to involve volunteer participants who have the medical or psychiatric condition that the new intervention is believed to improve.

However, in order to correctly detect the therapeutic capacity of the new intervention, it is normal in these trials to have at least two groups: an experimental group and a control group, two groups: an experimental group and a control group.. The experimental group will be made up of participants who are going to receive the intervention, with the intention of seeing what effects it has on their health, whether there is an improvement or worsening of symptoms. On the other hand, the participants in the control group will not be given any therapeutic treatment. Both the participants in the control group and the experimental group do not know which group they have been assigned to.

The objective of forming these two groups is to know to what extent the improvement (and also worsening) of the participants is attributable to the application of the intervention..

The idea is that if there is improvement in the experimental group and not in the control group, the improvement is attributable to the treatment. In the event that in both groups there is some improvement, it is not related to the intervention, but attributable to the course of the medical or psychiatric condition it is intended to treat. Indeed, there are medical illnesses and mental disorders that may improve simply with the passage of time.

Let's start at the beginning: the placebo effect.

So far it all makes sense, but a question surely comes to mind: if the experimental group receives the treatment to be tested, what does the control group receive? The volunteers in the control group have to receive something, otherwise they will know they are in that group and that is something we don't want. What we want in research is to test the pure and simple effectiveness of the treatment, and for that we need that those who are receiving it do not know that they are receiving it but show improvement if it is effective.

For this reason all the participants in the experiment receive something. If the experimental group receives the experimental treatment, the control group receives a placebo. A substance or placebo treatment is any intervention that those who apply it know or assume that it has no effect, no effect whatsoever, and no effect whatsoever. has no effect whatsoever, neither therapeutic nor detrimental.. For example, in pharmaceutical research, if the experimental group is given the drug that is believed to work, the control group will be given something that looks like a drug, in the form of a pill or syrup, but without any active component.

And this is where we have to talk about the placebo effect. This effect is essential to be taken into account in research, since it may well call into question the effectiveness of the new intervention. The placebo effect occurs when the control group, despite not receiving the experimental treatment, reports improvement.. The participants in the control group have the expectation of having received the experimental treatment, and believe that it is being applied to them, perceiving an improvement that is nothing more than suggestion.

It is important to understand that, before participating in an experiment, participants are given informed consent. It explains that the experimental treatment being tested may have both health benefits and unwanted health effects, and that the purpose of the experiment is to find out what these are. In addition, they are told that they may receive this treatment or they may be given a placebo. Despite knowing this information, it is not uncommon for participants to want to be part of the experimental group, and to believe that they have been assigned to that group, feeling a supposed improvement.

The use of placebo is the norm in randomized controlled trials.. The logic behind the application of placebos derives from the need to distinguish between the real benefit observed by the participant and the benefit that is a product of their desire to improve. The mind is very powerful and is capable of deceiving us, covering up symptoms and making us believe that we have improved.

Although the placebo effect has been known for quite some time and medical, pharmaceutical, psychological and psychiatric research has questioned it, the existence of two other effects given in an experimental context has been raised: the nocebo effect and the lessebo effect. Both effects are very important, like the placebo effect itself, and can in fact bias the interpretation of the results of the experiment.

The nocebo effect

Before talking more in depth about the lessebo effect it is worth understanding, briefly, what the nocebo effect is. "Nocebo" comes from Latin, meaning "I must harm", in contrast to the term "placebo", which is "I must pleasure". The knowledge of the nocebo effect is considered quite revealing about how everything related to placebo (ineffective intervention) and its homonymous effect should be applied and interpreted, given that even what should have no effect at all can do harm..

As we have already mentioned, the placebo effect is, in essence, the improvement perceived by the participants in the control group despite the fact that they have not been given anything known to have any effect. The nocebo effect would be the opposite: it is the worsening of symptoms or signs of a health condition due to the expectation, conscious or not, of undesirable effects of an intervention.

In experimentation, there is always an informed consent and, as mentioned above, it explains that the intervention may have undesirable effects. explains that the intervention may have both positive and negative effects.. If the placebo effect is to believe that the intervention is being received and that it has positive effects, in the case of nocebo it is also to believe that the intervention is being received, but that its adverse effects are manifesting themselves. The participant has pessimistic expectations that make him/her believe that the treatment is harmful to him/her.

What characterizes the lessebo effect?

For a long time, research was only concerned with monitoring the suggestion and expectations of the control group, both positive and negative. Under the logic that something must necessarily happen in the experimental group, both a therapeutic effect and adverse effects, the effects of suggestion in that same group were not monitored. Fortunately, although relatively recently, more attention has begun to be paid to how pessimistic expectations in the experimental group can override the actual therapeutic effects of the intervention.

If the placebo is the perceived improvement in the control group and the nocebo the worsening, the lessebo effect is the perception of less improvement, nullification of effects or worsening in the experimental group. is the perception of less improvement, reversal of effects or worsening in the experimental group.. That is, participants in the experimental group, who are receiving the treatment, believe that they have been given either a placebo or are suffering from the adverse effects of the treatment, believing that their condition is being worsened.

This may be due to multiple causes. It may be that, as would be the case with the nocebo effect, participants have a pessimistic view of the effects of the experimental treatment, thinking that they are more likely to suffer its unwanted effects rather than the therapeutic ones. Another thing that has been seen is that not a few participants, despite reading the informed consent, do not understand it, and think that "placebo" is synonymous with "harmful". They think that the experimental treatment is beneficial and that the control is necessarily bad.

Scientific implications

It is clear that both the placebo and nocebo effects affect research if they are not taken into account, but the lessebo effects are even worse.. As we have already mentioned, the participant who is receiving an effective treatment may think that it is either not effective or that it is a placebo, and he or she may auto-suggest that he or she is not improving or even getting worse.

Discarding something that, objectively speaking, is working but that the volunteers report as harmful due to their pessimistic expectations not only implies discarding a treatment that works, but also implies loss of economic resources and time. Whether it is a drug, a new psychological therapy or any other type of treatment, its design and application involves the mobilization of many efforts, and it is a real mistake for it to be discarded due to biases of the experimental participants.

It is for this reason that on the basis of the new research focused on studying the lessebo effect, it is necessary to consider how reliable is the lessebo effect. effect, it must be asked how reliable the participant isThe question of how reliable the participant is, in the sense of what kind of expectations he/she has about the experiment and whether he/she has an unrealistic style of thinking. Whether he tends towards pessimism or optimism, it is necessary to know this thinking pattern, and to find out to what extent that participant will not bias the results of the experiment.

Bibliographical references:

• Mestre, T. A. (2020) Nocebo and lessebo effects. International Review of Neurobiology 153, 121-146.
• Mestre, T. A., Shah, P., Marras, C., Tomlinson, G., & Lang, A. E. (2014). Another face of placebo: the lessebo effect in Parkinson disease: meta-analyses. Neurology, 82(16), 1402–1409. https://doi.org/10.1212/WNL.0000000000000340