Non-Deceptive Placebos Alter Neural Markers of Emotion Regulation

Post by Shireen Parimoo

What's the science?

There is a lot of debate and controversy surrounding the placebo effect because placebos – an inactive form of medication or treatment – generally improve symptoms like emotion and pain (also known as the ‘placebo effect’). Yet, the effect relies on the patient’s belief that the treatment is real, as they are often unaware of receiving a placebo rather than an active medication. This has raised several ethical concerns about administering placebos without the patient’s knowledge. To address this, emerging research has investigated the efficacy of ‘non-deceptive placebos’ (NDP) on subjective outcomes such as pain, anxiety, and well-being, but it is not known whether their effects extend to biological outcomes as well. This week in Nature Communications, Guevarra and colleagues used electroencephalography to examine whether non-deceptive placebo effects extend to neural markers of emotional distress.

How did they do it?

Two experiments were conducted to investigate the impact of NDPs on (i) self-reported emotional distress (N = 62), and (ii) neural markers of emotional distress (N = 198 females). Participants were randomly assigned to a non-deceptive placebo group or a control group and were educated about the effectiveness of placebos and how they can still work even without deception (non-deceptive placebo group) or about the neural basis of pain (control group). A saline nasal spray was administered to both groups; the non-deceptive placebo group was informed that the spray was a placebo but would reduce their experience of emotional distress if they believed it would, whereas the control group was told that the spray would improve the quality of physiological recordings.

Participants then completed an image viewing task in which they saw highly negative and neutral images. In the first experiment, they rated how much distress they felt in response to each image, which provided a subjective measure of the effectiveness of NDP. In the second experiment, electroencephalography recordings were obtained while participants completed a similar image viewing task. The authors were interested in the late positive potential (LPP), which is an event-related potential associated with emotional distress. The LPP consists of an early attentional component that occurs between 400-1000ms following image presentation, and a sustained component between 1000-6000ms that is thought to reflect conscious appraisals. This sustained LPP component is reduced by cognitive reappraisal strategies.

What did they find?

Emotional distress ratings for neutral images were similar across participants in both groups. The non-deceptive placebo group provided lower ratings for negative images compared to the control group, which is consistent with past research on the effect of NDPs on self-reported outcomes. The early component of the LPP did not reliably differentiate between the two groups, suggesting that NDPs do not affect the early attentional processing of emotional stimuli. In contrast, there was a widespread reduction in the sustained component in the non-deceptive placebo group that occurred around 2000-3000ms after the images were presented. This means that the immediate processing of the images did not differ between the two groups, whereas the NDP seemingly influenced the appraisal stages of emotional processing of the images. Interestingly, this reduction occurred for both the neutral and negative images in the placebo group, indicating that the NDP had a general effect on emotional distress rather than a specific effect toward processing negative images.

What's the impact?

This study is the first to demonstrate the neural and subjective impact of non-deceptive placebos on emotional distress. These findings are exciting because they open up the possibility of using NDPs as a treatment approach for managing psychiatric disorders characterized by emotional distress, such as depression. Further research is needed on the longer-term efficacy of NDPs and their potential generalizability to other populations and domains like pain management.

Guevarra et al. Placebos without deception reduce self-report and neural measures of emotional distress. Nature Communications (2020). Access the original scientific publication here.