Redefining the Placebo Effect

Placebos are often defined as ‘inert’, but this term from clinical research, is paradoxical – How can something inert have an effect upon the body? Furthermore, placebos can also include surgical interventions, psychological treatments, saline injections, sugar pills, but also conventional drugs which are administered to treat an unrelated condition i.e. if you were to give paracetamol to a patient to lower anxiety levels, because paracetamol would not have any standard pharmaceutical effect upon anxiety.

There is not one placebo effect, but many. These can be grouped loosely into two categories: conditioned and anticipatory responses. The venn diagram above, defines the differences between these two effects. The anticipatory response originates from the contextual cues of the placebo effect [see figure below] and can vary from culture to culture. It includes elements such as the hospital environment, a pill and medical examinations.

Wager Placebo Diagram

But the conditioned response is a direct response of the brain and/or immune system to a given stimulus. This response does not rely upon psychology or contextual cues and has even been demonstrated in animals. So how does it work? If a patient – or animal – was given medication in sweetened water for several days (the conditioning period), then the medication was removed, the patient would continue to respond to the sweetened water. This conditioned response has been found in many forms of medication: pills, liquid medicine, injections and can be very powerful. Unfortunately, this effect is usually limited in duration, but, studies have shown that it can make up a third of the treatment time without reducing efficacy. Harnessing the conditioned response is the primary focus of Yekize’s first project.

To return again to the venn diagram at the top of this page. The central point, where conditioned and anticipatory responses overlap, is of particular interest. It is anticipated, that treatments employing both the conditioned and anticipatory responses, are likely to have stronger effects. Much research still needs to be done in this area, but if the most powerful effects are to be found in this overlap, it is an area that needs to be explored further.

Finally, we shall confront one last myth about the placebo effect: that it always requires deception. The placebo effect does not always involve deception. For the conditioned response in particular, deception is not always required, because it is not thought to be psychologically mediated. However, deception can have a significant effect upon the strength of anticipatory responses. Current research is exploring the use of meta-placebos – where the patient is fully informed that they are taking a placebo. This research is predominantly being undertaken to explore how the placebo effect can be harnessed by primary care. The placebo effect is already commonly used in primary care, but discovering how we can do so, whilst keeping the patient informed, would be groundbreaking to the general approach.

To summarise:

Placebos are not ‘inert’, because they have direct effects upon the body.

There are at least two types of placebo effect: conditioned and anticipatory responses.

The conditioned response is a direct neuroimmune response by the body to a stimulus, following a period of conditioning.

The anticipatory response is a psychologically mediated response originating in the contextual cues of treatment.

Where these different types of placebo effects overlap, is thought to have the strongest effects.

The meta-placebo introduces informed consent to placebo treatments and is being explored continuously in current research.


Sources: Foot, D and Ridge, D. Constructing the placebo effect in the placebo wars: What is the way ahead? Health Sociology Review (2012) p355-369
Image Source: Wager, TD and Atlas LY. The neuroscience of placebo effects: connecting context, learning and health. Nature Reviews | Neuroscience 16 (2015) p403-418.

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