A magazine for friends of the Warren Alpert Medical School of Brown University.

The Power of Negative Thinking


The nocebo effect can worsen symptoms and side effects, and even cause illness.

At the time of this writing, worldwide there have been more than 686 million confirmed coronavirus cases and more than 6.8 million COVID-19 deaths. A staggering 12.7 billion doses of the COVID vaccine have been administered around the world. Undoubtedly, the vaccine has saved countless lives. However, the vaccine has not been universally accepted. This may be partially attributed to the nocebo effect.

The Nocebo Effect: When Words Make You Sick
By Michael H. Bernstein, PhD, Charlotte Blease, PhD, Cosima Locher, PhD, and Walter A. Brown, MD
Mayo Clinic Press, 2024

A substantial proportion of the population is wary of the vaccine, and 20 percent of Americans have not received any vaccination. Concern over adverse effects is fueling resistance. And vaccines do have some specific side effects, which are widely discussed in news outlets. A CBS News article, titled “Should You Plan a Sick Day in Case of COVID-19 Vaccine Side Effects?” suggests that people plan for one or two days off work after receiving their shot. One Fox News article quotes a CDC expert who said that “people should be prepared to have … a low-grade fever.” Countless online discussion boards teem with anecdotes of people feeling sick after getting jabbed.

Lost in this discussion of side effects, and largely overlooked by the CDC, vaccine experts, and the media, is the inconvenient fact that a significant portion of these side effects are likely not actually caused by the vaccine. Instead, they are the result of our negative expectations, the so-called nocebo effect. The first telltale signs of nocebo response with the COVID vaccine came from the initial efficacy and safety trials. In these vaccine trials, one group of participants received the real COVID-19 vaccine, while another group was injected with saline. Several studies found a large overlap in the types of side effects reported by participants who received the actual vaccine and those who received the placebo injection of saline. One review estimated that the nocebo effect could account for 76 percent of the side effects from the COVID-19 vaccine.

“Nocebo” stems from the Latin word nocere, which translates roughly as “to harm.” Some experts view it as a kind of negative placebo effect in which the outcome is undesirable, such as a headache or stomachache, while the placebo effect, such as feeling less pain or depression, is desirable. The nocebo effect has been called “the placebo effect’s evil twin.” In our view, the nocebo effect can be summarized as “the occurrence of a harmful event that stems from consciously or subconsciously expecting it.” The core of the nocebo effect is that adverse health effects occur as a result of negative expectations.

The mind’s unfortunate ability to cause suffering is well established, and this phenomenon lies at the heart of the nocebo effect. One such example, known as “The June Bug,” occurred in a textile factory in the United States in the early 1960s. Many employees began to feel dizzy and had an upset stomach. Some people vomited. Rumors of a mysterious bug that was biting employees began to circulate and eventually 62 people who worked at the factory became ill. So what were these mysterious bugs? According to experts, they were nothing—literally. The CDC investigated this outbreak, but no bugs or any other cause of the illnesses could be identified. It instead appears to have been a case of what has often been labeled “mass hysteria,” though it is now called psychogenic illness.

The nocebo effect is particularly relevant regarding drug side effects. Consider the case of statins, a class of cholesterol-lowering drugs that are very commonly prescribed. There is considerable evidence for the safety and efficacy of statins. Statins effectively reduce low-density lipoprotein (LDL) cholesterol—the so-called bad cholesterol. Although statins are very effective at reducing LDL cholesterol, many patients stop taking them due to side effects such as muscle aches or joint pain. However, would these patients have experienced such “side effects” even if they hadn’t taken a statin? In other words, could the nocebo effect explain why many patients stop taking statins? Judith Finegold and her colleagues conducted a systematic review that analyzed data from 29 clinical trials in which 83,880 patients were randomly assigned to receive either a statin or a placebo, in double-blind fashion. The overall conclusion of the study was: “Only a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo.” For example, symptoms such as nausea, muscle aches, fatigue, diarrhea, and constipation were no more prevalent in the statin group than in the placebo group.

The nocebo effect can arise as the result of encountering any negative health expectation, and the consequences can be large. In early 2023, a group of researchers led by Siddhartha Roy looked at data from 2011 to 2019 and proposed that the nocebo effect may even have played a role in the Flint water crisis. As American readers will remember, the Flint water crisis was a major scandal in 2014 after water in the city of Flint, Michigan, was found to have been contaminated with lead. Parents, teachers, and members of the public were understandably concerned about how this would harm the intellectual development of children. The onset of the water crisis did in fact coincide with a worsening of educational outcomes, with more students entering special education. However, and this is the critical part, the percent of children with an elevated blood lead level in Flint was always lower than the nearby city of Detroit, and almost always lower than the state of Michigan as a whole. Unlike Flint, neither Detroit nor the state experienced an increase in special education. Furthermore, while there was indeed a temporary increase in the number of Flint children with an elevated lead rate during the worst of the water crisis, the overall trend over the course of several years was a substantial reduction. What do we think caused the children to perform worse at school? Was it the water? Or might it have been the fact that, as the researchers put it, “several teachers openly expressed their belief that Flint children had been brain damaged, were incapable of learning, and that there was little point in trying to teach them”?

Health, vitality, and well-being are all critical. As a society, we invest considerable sums in state-of-the-art facilities to develop new treatments and cures. We mandate that physicians undergo years of intensive training in biology, anatomy, and chemistry before they can treat a patient unsupervised. But as mundane as it sounds, mere language is important too. Words can make us sick. Let’s choose them carefully.

Michael H. Bernstein, PhD, and Walter A. Brown, MD, are coeditors of The Nocebo Effect: When Words Make You Sick. This essay was adapted from book chapters written by Bernstein, Brown, Charlotte Blease, Cosima Locher, Kate MacKrill, and John M. Kelley.


Comments are closed.