Does the Placebo Effect Work When You Know It’s a Placebo?
Post by Christopher Chen
The takeaway
Placebos can provide emotional and physiological benefits, but their use raises ethical questions due to the use of deception. New evidence suggests off-label placebos (OLPs) which do not rely on deception, may also have positive health benefits.
What's the science?
Placebos are a form of patient treatment that have no inherent therapeutic value (e.g., sugar pills, saline injection). However, studies time and time again have validated a “placebo effect,” where people who take placebos may still undergo physiological changes that enhance overall health. For example, functional brain imaging reveals placebos can modulate brain circuits associated with emotional regulation and pain, resulting in a painkilling effect. However, ethical concerns surround the use of traditional placebos because they are given to patients who believe the placebo has therapeutic value. To avoid this, researchers have turned to the use of open-label placebos (OLPs), or placebos that patients know have no therapeutic value. Recent studies show patients taking OLPs report symptomatic relief from maladies like depression, anxiety, and irritable bowel syndrome. However, whether OLPs elicit neurological changes like conventional placebos remains unclear. In a recent article in Neuropsychopharmacology, Schaefer et al. reveal that people taking OLPs exhibited enhanced activity in regions associated with emotional regulation and pain, suggesting OLPs do elicit neurological changes even when people know they are placebos.
How did they do it?
Researchers ran two experiments: one tested the effects of OLPs on participant mood and the other tested OLP effects on brain activity. In the first experiment, participants were divided into two groups. One group was told a nasal spray they were taking was an OLP and potentially had health benefits, while the other group was told the nasal spray was a necessary part of the experiment. Following the administration of the nasal spray, both groups went through the same visual task of ranking a series of pictures depicting neutral images or images designed to elicit strong negative feelings. Following the presentation of each picture, participants described their emotional state. The second experiment played out similar to the first, but participants were instead shown the images while inside an MRI (magnetic resonance imaging) machine undergoing an fMRI protocol designed to gauge blood flow as a measure of brain activity. In this experiment, the description of emotional state was given after the MRI portion was complete.
What did they find?
In the first experiment, researchers found that participants from both groups responded similarly to the neutral images, but that participants who were told of the health benefits of OLPs reacted less strongly to the emotional images, suggesting placebos can still help people emotionally regulate even when they know it is a placebo. The second experiment went a step further, showing that the OLP group had greater activation in two regions also known to be activated by traditional placebos, the periaqueductal gray (PAG) and anterior cingulate cortex (ACC). Interestingly, there were two additional key differences in the neural signature of OLPs: 1) activation in the hippocampus, a brain region not known to be activated by normal placebos, and 2) no activation in the prefrontal cortex, a region known to be activated in normal placebos.
What's the impact?
The present study reveals that OLPs elicit activation patterns in the brain that are distinct from patterns associated with traditional placebos. The authors suggest that the lack of PFC activation in OLP treatments may indicate that the PFC is somehow linked to brain processing of deception. The activation of the hippocampus in OLP treatment but not conventional placebo treatments may also indicate how removing deception from the placebo effect may activate more hippocampal-driven processing of emotion and pain. While more research is needed to further validate these findings, this work suggests that the placebo effect holds, even when we know it’s a placebo.
