A QUICK SPRAY into the nose, a small sugar pill, or a fake surgery—placebos have taken many forms throughout history, and they have shown that expectation may produce results as powerful as a drug. But there has been one constant throughout: deception. A doctor or therapist has always had to lie to their test subject or patient about which version of a treatment they are getting.

Lead author Darwin Guevarra, a postdoctoral researcher in UM’s psychology department, has long been fascinated with placebo literature, including a 2013 pilot study finding that non-deceptive placebos mitigated symptoms of major depressive disorder. To him, it suggested that this could also be a way to address other mental health disorders. So Guevarra decided to test placebos in the context of emotional regulation, or the ability to control an emotional response, which is dysregulated in many mental health conditions. “Emotions robustly respond to [expectations]. That's why we thought that this was the best domain to look at,” he says. He wanted to find out if non-deceptive placebos would be able to reduce emotional distress, and if so, to find a corresponding brain mechanism that could explain what was happening.

In the first phase of his study, Guevarra and his colleagues recruited 62 healthy college students: One group of participants read about the placebo effect and then were told they would receive a placebo, while another group read about pain management and were kept in the dark about their treatment. Next, the researchers sprayed a saline solution into each person’s nose. For the non-deception group, the students were told prior to receiving the saline solution that it was a placebo. In the group that was deceived, they were told the saline solution would help obtain better physiological recordings. (It wouldn’t—the spray actually does nothing.)

Next, the students looked at distressing images on a screen, such as a person with an open injury. Immediately after seeing each picture, participants rated how it made them feel, with 1 being not at all negative and 9 being very negative. Overall, those who had been told they received a placebo felt less distress in response to seeing the pictures. The non-deceived group rated their distress lower—a 6 on average—than those that had been deceived, who on average reported feeling around 7.5 on the distress scale.

But this study had a twist. Most previous studies only used self-reported measures like questionnaires to ask subjects to rate how depressed, anxious, or stressed they feel. These are subjective evaluations, which may be influenced by response bias, in which participants do not accurately report what they are feeling. Instead, Guevarra’s team wanted to obtain an objective neural measure about what happens in response to non-deceptive placebos. Again, they recruited 198 healthy college students and gave them the saline spray placebo, with and without deception. This time, while showing the participants the negative pictures, they measured the electrical activity in each person’s brain using electroencephalography. EEG measures the electrical signals emitted from the entire brain, as recorded from electrodes stuck to the participant’s head.

When the researchers looked at the EEG readings from the two groups, they saw that the magnitude of the LPP of participants in the non-deceptive placebo group was smaller than those that had been deceived, meaning that their brains responded less to the distressing images than the other group. Three seconds after they were shown the distressing image, participants who received the non-deceptive placebo had an LPP amplitude of about 0.5 microvolts, while those that did not had an amplitude of about 3 microvolts. An analysis of this difference revealed that non-deceptive placebos had a moderate effect on the LPP over the control conditions, suggesting that they can modulate and dampen early neural reactions to emotional distress. In other words, the spray worked—even though participants knew it was a fake.

For Guevarra, this was evidence that the effect of the placebos was not response bias, but rather a real change in the brain. “I think it's a genuine psychobiological effect,” he says. “The manipulation we have really fine-tunes and leverages people's expectations.”

How might this work translate to the real world of mental health treatment? While the idea is still theoretical, Guevarra feels that non-deceptive placebos might be tried for conditions that consistently respond to expectations, such as anxiety, depression, and pain—and for mild to moderate cases. He envisions them being used by therapists as a first, cost-effective step or as co-interventions, given along with established treatments such as antidepressants and cognitive behavioral therapy, a type of talk therapy that has become an important tool in psychology. “Let's give them placebo pills first and see how it goes,” he says.

If the placebo doesn’t work, then they could move on to other alternatives. “The beauty of this is that it’s relatively low-cost and arguably side effect-free,” says University of Michigan psychology professor Ethan Kross, the principal investigator on the study.

Read the full article at Wired.