Nocebo ― a placebo's evil twin

"Somebody tells you 'God, you look terrible, are you going to be sick?' and then suddenly you are," said Charlotte Blease, recalling a recent bus trip in Ireland, from Belfast to Dublin. "You have this expectancy and it ramps up the symptoms."

Blease ― a health researcher at Uppsala University, Sweden, and one of the authors of "The Nocebo Effect: When Words Make You Sick" ― was feeling nauseous with motion sickness. 

She was trying to distract herself with any other thought, and knew that if someone interrupted her, it would trigger the nocebo effect. 

"The nocebo effect [is] negative health outcomes that arise from negative expectations," Blease told DW. It can exacerbate feelings of pain, anxiety, nausea and fatigue.

Nocebo: Not placebo

The nocebo effect is the negative mirror image of the placebo effect.

Imagine a medical trial. One group is given a real medication to treat headaches. The other group gets sugar pills, without an active ingredient.

When patients in this second group report an alleviation of their headaches, doctors say the patients are experiencing a placebo effect ― because they thought they were taking painkillers, like the patients in group one, positive thinking led to a positive outcome in their treatment.

It's a medically recognized phenomenon. And the nocebo effect is slowly gaining a similar recognition by health professionals, except it's the exact opposite: it's when negative thinking influences your outcomes, negatively.

Nocebo effect, COVID and vaccine hesitancy

During the coronavirus pandemic, researchers found that people's expectations before a COVID-19 vaccination could be linked to how they felt afterwards.

A team of scientists from Israel and the UK looked at a group of 756 Israeli adults over the age of 60 years. Each had received a booster shot ― a third vaccine against COVID-19.

"We measured both vaccine hesitancy ― one's negative attitude or expectations towards the vaccine ― and the number of subjectively reported side effects," said Yaakov Hoffman, lead author of the study and a professor in the Department of Social and Health Sciences at Bar-Ilan University, Israel.

Published in the journal Scientific Reports in December 2022, their results indicated that people who had negative expectations before their second shot were more likely to experience side effects after their third.

"The more anxiety about the vaccine, its safety and its side effects [one felt], the greater one would actually experience side effects," Hoffman told DW. 

And when the nocebo effect and vaccine hesitancy were combined, he said, it had the potential to become a vicious circle: A person who was hesitant to get vaccinated, perhaps because they had read about side effects online, would be more likely to experience side effects. Those side effects would then be recorded and reported by their doctor. That, in turn, would contribute to more media coverage about side effects, and more people feeling hesitant about vaccines… and so on, and so on.

How doctors deal with the nocebo effect

Talking to patients without triggering the nocebo effect can be a challenge.

"Doctors are obligated not to harm the patient, or to mitigate harm where possible, but they also have an obligation to tell the truth," said Blease.

In the case of a vaccine with relatively minor side effects, said Hoffman, addressing the nocebo effect head-on could make sense.

"Perhaps it's better to call a spade a spade and say, 'There's a certain percent of side effects which you are experiencing that are nocebo effects. Which means you are really experiencing them, but it doesn't necessarily signify danger,'" he said.

Hoffman stressed, however, that this was only speculation and that further research was needed to provide firm evidence.

Importance of framing health information

Other experts in the field agree the way that doctors communicate with patients can help prevent nocebo effects.

"How doctors talk to patients can influence therapy outcomes," said Ulrike Bingel, a clinical neurosciences professor who heads a pain research unit at University Hospital Essen, Germany.

"So far, communication has been mostly viewed as a feel-good issue. We need a higher awareness of how crucial it is," Bingel said.

When it comes to vaccines, for example, doctors are required to disclose any possible side effects.

But instead of rattling off a list of side effects that might scare a patient, Bingel said doctors should frame side effects as a sign that the immune system is working well.

This way, the patient might have fewer negative expectations and experience fewer or less-pronounced side effects.

Nocebo effect may be evolutionary

But how can negative ideas in our mind affect what's going on in our body?

First, it's important to understand that the nocebo effect is real. It's not a figment of a patient's ― pessimistic — imagination. 

"The nocebo and placebo effects involve complex neuroscientific processes," Bingel told DW. "When you're experiencing a nocebo effect, your body stops pumping its pain brakes. Your brain receives more brain impulses and you feel more pain."

The problem is, researchers can't explain why this happens. Not yet. But they do believe it may have something to do with our evolution.

"It was important that our ancestors learned from coming into contact with a wild animal or a poisonous plant," said Bingel. "The body [got] prepared for next time."

In other words, an early human's negative expectations would have prepared them, just in case they had to run for their lives.

"The nocebo effect could be a hangover from the past," said Blease, [but] that's a mismatch for today's modern medical environment."

Edited by: Zulfikar Abbany

Sources:

The Nocebo Effect: When Words Make You Sick by Michael Bernstein, Charlotte Blease, Cosima Locher, Walter Brown. Mayo Clinic Press, March 19, 2024.

Vaccine hesitancy prospectively predicts nocebo side-effects following COVID-19 vaccination by Y.S.G. Hoffman, Y. Levin, Y. Palgi et al. Scientific Reports, 2022: https://doi.org/10.1038/s41598-022-21434-7