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FDA draft guidance posted in June 2023 provides a potential framework on how to overcome expectancy bias and the nocebo effect by employing an active placebo which could be a substance that also has mind-altering effects but no expected therapeutic benefit.

Conversely, those who received the placebo may have experienced a nocebo effect, which means worsening symptoms because they were aware they did not get active treatment.

"Drug effects can be ruled out in the placebo group, which means the symptoms either arose by chance, independently of the treatment, or they are the product of the nocebo effect," Henssler explains.

The nocebo effect is often considered the mirror image of the placebo effect.

The more likely explanation is an anxiety reaction or a similar psychosomatic response, like the “nocebo effect.”