The Placebo Effect

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The placebo effect refers to the therapeutic response which occurs as a consequence of an inert treatment. The “treatment” in cause can be either a tablet, an injection or even surgery.

Placebo interventions are used in clinical trials in order to determine whether a medical treatment has a true effect, independent of the expectations of efficacy, which could influence the results of the trial.

It’s important to note that, even though clinical trial participants don’t know whether they will receive the active ingredient or the placebo treatment, they are informed beforehand about the chance of receiving an inactive treatment.

Nevertheless, the practice of using placebos in clinical trials is not without controversy. Some scientists argue that it’s unethical to withhold treatment, be it even experimental, from people who need it. In addition, in cases where a treatment for a disorder already exists, this should be used as control instead of the placebo intervention.

The rationale behind is two-fold. On the one hand, new therapies should be better than already existing ones, otherwise there is no point in investing money and resources in their development. On the other hand, patients should not be left without a treatment during the clinical trial period if a treatment already exists.

But how do placebos even work? Generally speaking, they change the way in which patients perceive their condition, without actually affecting the disease. Yet, the neural mechanisms through which placebo interventions produce these effects are unclear. But there is one exception here: pain.

In pain, it appears that placebos increase activation both in areas associated with cognitive control, such as the dorsolateral prefrontal cortex and the anterior cingulate cortex, as well as in areas which are part of the descending pain modulating system, such as hypothalamus and the periaqueductal gray.

Finally, it’s important to note that there are also factors which confound the placebo response effect itself (i.e. they make it seem like a placebo effect is present when there isn’t any, a sort of meta-placebo, if you will). These include regression towards the mean (the tendency of symptoms to recede towards the baseline), as well as response bias from participants (responding more positively out of politeness, for example).

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References

Brown, V., & Peciña, M. (2019). Neuroimaging studies of antidepressant placebo effects: challenges and opportunities. Frontiers in psychiatry, 10, 669.

Kottow, M. (2010). The improper use of research placebos. Journal of evaluation in clinical practice, 16(6), 1041-1044.

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