Think you are sick? It may be the nocebo effect.

[aum]

Negative beliefs or expectations about a treatment or experience may elicit symptoms of feeling sick, even when the intervention is a sham.

 

(iStock)

 

Have you ever walked out of a jam-packed concert or restaurant with a scratchy throat, worried that you just caught a virus? Or swallowed a medication and felt immediately unwell?

 

If yes, you’re personally familiar with the nocebo effect, though you probably didn’t know that’s what it’s called.

 

The nocebo effect is the opposite of the placebo effect — “the evil twin or the dark side of the placebo effect,” said John Kelley, distinguished professor of psychology at Endicott College in Beverly, Mass., and deputy director of the program in placebo studies at Beth Israel Deaconess Medical Center. “It’s a negative version of the placebo effect, where people are suffering more than they otherwise would because of their negative expectations.”

 

With the placebo effect, someone might gradually feel better after swallowing a pill, getting a therapeutic injection or receiving another medical treatment, even if what they were given is an inert treatment. With the nocebo effect, negative beliefs or expectations about a treatment or experience may elicit symptoms of feeling sick, even when the intervention is a sham.

 

It’s hard to quantify how common the nocebo effect is, because it’s rarely measured in clinical trials or in doctors’ offices, but there are some hints. A recent study involving people with inflammatory bowel disease found that 13 percent experienced a nocebo effect — defined as new or worsening symptoms without objective evidence of active disease activity — in the first six months after switching from one medication to a biosimilar drug, despite both drugs having similar clinical effectiveness. Among the researchers’ conclusions: “Misperceptions and negative attitudes toward biosimilars may contribute to the development of nocebo effects and therapy cessation.”
 

A 2022 review of clinical trials found that 29 percent of people who were given a placebo (inactive) coronavirus vaccine reported having fatigue and 27 percent reported a headache from the vaccine. The researchers chalked these symptoms up to people’s negative expectations about the side effects of the vaccine, leading to a self-fulfilling prophecy “whereby the belief that a future event will occur contributes to the actual occurrence of that adverse reaction.”

 

The nocebo effect also has been associated with people’s adverse reactions to statin drugs and antidepressants, heightened pain perception with various interventions, changes in motor function in response to medications or manipulative techniques in the sports setting, and more, experts said.

 

“It’s something we’re all susceptible to, to some degree,” said Kelley, also a lecturer on medicine at Harvard Medical School. “Even though it starts psychologically, it’s a biological process, too, at the level of neurotransmitters and endogenous opioids.”

How the nocebo effect happens

 

The precise mechanisms behind the nocebo effect aren’t well understood. One theory is that it relates to the notion that your expectations can influence your response to a medical treatment. Another has to do with conditioning — how experiences from the past could affect your current experience. This is why people with cancer who are being treated with chemotherapy sometimes experience nausea “when they enter the room before they get the IV,” said Luana Colloca, distinguished professor of medicine and director of the Placebo Beyond Opinions Center at the University of Maryland.

 

Another possible mechanism relates to misattribution — in this case, you may “have some kind of minor ailment and you attribute it to a drug or medical procedure rather than what actually might be causing it,” explained Michael Bernstein, a psychologist and an assistant professor of diagnostic imaging at the Warren Alpert Medical School of Brown University. If you have a headache, for example, and you just started taking a new medication, you might blame the drug, rather than work stress, barometric pressure changes, or caffeine withdrawal if you missed your morning cup of coffee.

 

Plus, “negative expectations can cause anxiety, which can release stress hormones and stomach acids that can cause negative symptoms,” said Suzanne Helfer, a professor of psychology at Adrian College in Adrian, Mich.

 

The nocebo effect can also happen when health-care professionals provide verbal information about possible negative side effects. Research has found, for instance, that negative verbal suggestions about pain can induce anticipatory anxiety in patients and trigger the release of cholecystokinin, a hormone that facilitates pain transmission.

 

“Sometimes we, as clinicians, influence this terribly,” Colloca said. “Framing effects are so relevant when clinicians describe a diagnosis” or prescribe a drug.

 

The power of suggestion packs a potent punch when it comes to the nocebo effect.

 

A 2024 study in the Journal of Pain found that people who were conditioned with instructions to pay attention to pain had greater anticipatory anxiety and experienced greater pain intensity to a painful stimulus than those whose attention wasn’t directed in this way.

 

In another study, 38 women were presented with an odorless liquid (distilled water) and warned that it had an aversive odor that triggers feelings of disgust. Then the participants were shown disgusting, fear-inducing, and neutral pictures and their affective and neuronal responses were monitored on functional magnetic resonance (fMRI) imaging. The results: 76 percent of the participants reported perceiving a slightly unpleasant odor from the harmless liquid and greater disgust during the presentation of disgusting images when the fluid was present.

 

Guarding against the nocebo effect

 

To sidestep the nocebo effect, be an informed medical consumer or patient. “Simply understanding what the nocebo effect is could go a long way in ameliorating it,” Bernstein said.

 

Remind yourself that negative expectations could trigger side effects or influence your response to a treatment. “Switching negative expectations to more positive expectations can reduce negative symptoms like anxiety and fatigue,” Colloca said.

 

Try to maintain an open mind when taking a new medication or embarking on a new treatment. That doesn’t mean ditching your health-savvy at the door. It means asking your physician or pharmacist about side effects and how likely they are to happen, and then checking that information: If a health-care provider tells you that 10 percent of people experience a headache or nausea while taking a particular drug, put that in perspective by noting that 90 percent don’t, Kelley advised.

 

When prescribing a new medication, physicians can engage in “authorized concealment,” with your permission, and not tell you about possible minor side effects that are associated with the drug, said Bernstein, an editor of “The Nocebo Effect: When Words Make You Sick.” They would mention serious side effects that warrant a call or follow-up visit with the physician but not provide a rundown of every possible side effect.

 

If your health-care provider doesn’t offer this option, and you know you’re likely to feel anxious about this, Bernstein suggested saying, “I don’t want to know the whole laundry list of possible side effects. Please just tell me about the most likely or worrisome ones.”

 

“If you’re taking a medication that causes dangerous side effects, you want to know about it but with minor side effects, you may want to skip reading the leaflet until you do experience a side effect,” Helfer said. “Don’t preload your brain with things you can worry about.”

 

Source