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The Latest Findings on Open-Label Placebo Effects

Updated: Jan 18


Open-Access Article on the Neural Underpinnings of Open-Label Placebo Effects in Emotional Distress

Schaefer, M., Kühnel, A., Schweitzer, F., Enge, S., & Gärtner, M. (2023). Neural underpinnings of open-label placebo effects in emotional distress. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 48(3), 560–566.

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What is the science?

Placebos are inert interventions that can produce a significant clinical response. The symptoms and therapeutic response are real and measurable in a placebo response. Placebos can be pharmacological (e.g., drug), procedural (e.g., surgeries), psychological (e.g., conversation), and environmental (e.g., the clinic setting). Open-label placebos (OLPs), administered with full disclosure to the patient, are emerging as an ethical alternative. OLPs can produce clinical improvement, particularly for conditions that wax and wane, like depression and anxiety. The study explored whether OLPs induce similar neurological changes to traditional placebos. The anterior cingulate cortex (ACC), anterior hippocampi, and periaqueductal gray (PAG) modulate emotional distress.

What is the takeaway?

Open-label placebos (OLPs) demonstrate health benefits without the ethical dilemma of deception inherent in traditional placebos. OLPs activate brain networks that modulate emotional distress even when patients are informed they are placebos.

How did they do it?

The researchers conducted two experiments. After administering a saline nasal spray, the first experiment assessed OLP effects on mood while viewing emotionally distressing and neutral pictures. The second study evaluated brain activity via functional magnetic resonance imaging (fMRI) while viewing the same images following the saline spray.

What Did They Find?

Experiment one showed that OLP-informed participants exhibited better emotional regulation when exposed to emotional stimuli. In the second experiment, the fMRI showed greater activation in the hippocampi, periaqueductal gray (PAG), and anterior cingulate cortex (ACC) compared to the placebo group, similar to traditional placebos. However, the researchers did not observe the activation of the prefrontal cortex seen in traditional placebos.

What is the impact?

OLPs reduced emotional distress while viewing emotionally charged negative images. This study revealed unique brain activation patterns for OLPs compared to traditional placebos. OLPs activated the hippocampi, periaqueductal gray, and anterior cingulate cortex but not the prefrontal cortex. This work expanded our understanding of OLP efficacy and mechanism.


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