Experts Explain the ‘Nocebo Effect’ and How to Stop It
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Lauren Quinn has had health-related anxiety for most of her life—and the Covid pandemic didn’t do her any favors on that front. During the pandemic, she’d often feel a tickling sensation in her throat while she was at the grocery store or running errands and worry that she must have just caught something; by the next day, though, her symptoms would be gone. In 2022, she decided to start taking medication for her anxiety, but things didn’t go the way she’d hoped. “Within minutes of swallowing the first dose, I felt lightheaded and jittery and had massive heart palpitations—before I had even absorbed the medication,” says Quinn, 47, a science writer and mother of two in Urbana, Illinois. “I didn’t make it past the second day with the medication,” she says, because the symptoms were so distressing. Quinn didn’t know it at the time, but she was experiencing the nocebo effect.
But what is the nocebo effect, and what are some examples? Experts explain everything you need to know about experiencing negative thinking about health.
What is the nocebo effect?
In this phenomenon, the converse of the placebo effect, negative thoughts or expectations about experiencing a physical effect from a health-related action may elicit unpleasant symptoms. If you’ve ever walked out of a crowded restaurant with a suddenly stuffy nose, thinking you just caught a cold or COVID-19, or you immediately felt unwell after swallowing a medication, you’re personally familiar with the nocebo effect. “One way to describe it is as the evil twin or the dark side of the placebo effect,” says John Kelley, Ph.D., a distinguished professor of psychology at Endicott College in Beverly, MA, and deputy director of the program in placebo studies at Harvard Medical School.
With the placebo effect, you might feel better after swallowing a pill, getting a medication injection, or receiving another supposedly therapeutic intervention, even if what you were given is nothing more than a sugar pill, a saline injection, or another fake treatment. You received something that isn’t actually treating what ails you, but you ended up feeling better simply because you expected to. By contrast, “The nocebo effect is an undesired or negative effect of any sort of treatment or procedure that stems not from the treatment itself but from your expectations or from environmental variables,” explains Suzanne Helfer, Ph.D., a professor of psychology at Adrian College in Michigan.
How common is the nocebo effect?
The nocebo effect is fairly common, experts say, but it’s difficult to quantify how common it is, partly because (unlike the placebo effect) it is rarely discussed in the context of clinical trials or doctors’ offices. But there are some clues. A pair of studies published in the August 2022 issue of the journal Health Psychology found that people who believed they would have severe symptoms if they got infected with COVID-19 symptoms were likely to have COVID-like physical symptoms three weeks later—even though they weren’t actually sick with COVID. And a study in Europe found that up to 29% of people who were given an inert COVID vaccine reported having fatigue and up to 27% reported headaches from the vaccine. A nocebo effect “doesn’t mean it’s all in your head—people are really experiencing symptoms,” Kelley says. It’s just that the symptoms are triggered by your thoughts and expectations rather than the treatment itself.
Who is likely to experience the nocebo effect?
People who are prone to anxiety or negative thinking or who have an intense fear of pain or have experienced unexplained medical symptoms or conditions in the past may be especially susceptible to the nocebo effect, experts say. But no one is immune to it. “I’m sure everyone has experienced a nocebo reaction at some time because there are many different nocebo effects,” says Luana Colloca, M.D., Ph.D., a professor in the department of pain and translational symptom science in the School of Nursing at the University of Maryland in Baltimore, and director of the Placebo Beyond Opinions Center.
“So people should know about the nocebo effect and be alert to negative reactions.”
After all, the nocebo effect can affect your health by triggering new symptoms, worsening symptoms you already had, or affecting your adherence to a treatment regimen. “If you’re apprehensive about a medication to begin with, you’re likely to experience side effects that aren’t caused by the biological activity of the medicine,” explains Arthur Barsky, M.D., a professor of psychiatry at Harvard Medical School and coauthor of Feeling Better: A 6-Week Mind-Body Program to Ease Your Chronic Symptoms. Because of those side effects, the nocebo effect “might cause you to stop taking a medication or avoid a treatment you need or stop going to the doctor, which could make a chronic health condition worse.”
Nocebo effect examples
Beyond COVID, there are plenty of examples of the nocebo effect in action. In the research setting, it has been linked to people’s adverse reactions to statin drugs and antidepressants, increased pain in response to changes in dressings for chronic wounds, increased side effects following switches to generic medications, or heightened pain perception with various interventions. In real life, if you have bad eczema, you might start feeling itchy when you see a commercial for an eczema treatment on TV. Or, if you’re sensitive to gluten and think you just ate something that contained it (but didn’t), you might suddenly feel unwell. And folks often get known side effects when it’s too early for the drug to have kicked in, notes Dr. Colloca. “Sometimes people take a pill and immediately feel sick when they haven’t even metabolized the drug yet.”
Why does the nocebo effect happen?
Exactly how the nocebo effect occurs isn’t well understood but there are theories. One reflects the fact that your expectations can affect your response to a medical treatment. Another relates to how your experiences from the past (a.k.a., conditioning) might affect your current experience: For example, if you have anxiety about experiencing motion sickness, based on your previous history, you might start to feel nauseous before a car or boat you’re on even starts moving. A similar phenomenon can happen with anticipatory nausea and chemotherapy: “Cancer patients who receive chemotherapy sometimes experience nausea when they enter the room before they get the IV,” Dr. Colloca says.
Jennifer Golbeck can attest to this. A competitive long-distance runner, Golbeck has had numerous surgeries for sports injuries, and once she had a bad reaction to a particular form of anesthesia, which she has fastidiously avoided ever since. Nevertheless, “I always get really worried about the effects of any anesthesia and I ask lots of questions about how it’s likely to affect me,” explains Golbeck, 46, a professor of information studies at the University of Maryland. After she had surgery, using a different anesthesia, last November to correct her deviated septum, she couldn’t get off the couch for six days. The surgery went smoothly and she wasn’t taking pain medications afterwards so those factors weren’t to blame. “Being that exhausted made no sense because the anesthesia was out of my system within a day,” she says. “I knew it was my brain causing the problem based on my expectations and worries but I couldn’t over-ride it.”
“The brain has a predictive mechanism—your thoughts, beliefs, expectations, and worries factor into what you ultimately experience,” explains Dr. Barsky. This may have happened to Quinn, as well: When she was initially considering getting an IUD, whenever Quinn thought or read about the insertion procedure, she’d feel so faint that she’d have to lie down. Then, when she actually had an IUD inserted in 2012, sure enough: She felt faint and a bit shaky—her expectation had come true.
Another possible mechanism behind the nocebo effect relates to misattribution. “In daily life, healthy people have symptoms, and they don’t attach any medical significance to them,” notes Dr. Barsky, who has studied somatic symptoms, placebo effects, and nocebo effects. But if you’re told that these common symptoms such as headaches, insomnia, or fatigue can occur with a particular medicine you’re taking, you might reattribute the symptoms you were already experiencing to the drug and the symptoms then become magnified from your worry. “The expectations and suspicions change your understanding of the sensations and symptoms you are experiencing,” Dr. Barsky adds. Let’s say you just started taking an anti-hypertensive drug and that afternoon you develop a sinus headache as a storm approaches your area: You might convince yourself that the headache came from the medication instead of remembering that barometric-pressure changes are a major headache trigger for you; not only does this make you feel worse but it also makes you wary of taking the anti-hypertensive drug the next day.
Interestingly, there may be a neurobiological basis for the nocebo effect, as well as a psychological one. These predictions and expectations activate a series of pathways in the brain, from the prefrontal cortex through the brain stem, that affect sensory perception, including pain, and behavior, explains Tor Wager, Ph.D., a professor of psychological and brain sciences at Dartmouth College. Indeed, research has found that anticipatory anxiety can lead to elevated arousal of the autonomic nervous system, resulting in increased pain sensations during the administration of a painful stimulus or sham treatment. In other words, the nocebo effect can make you hurt more.
On its own, the power of suggestion can also pack a wallop, neurologically speaking. Case in point: In a study in a 2018 issue of the journal Brain Imaging and Behavior, 38 women were presented with an odorless liquid (distilled water) and warned that the fluid had an aversive odor that enhances 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 findings: 76% of the participants reported perceiving a slightly unpleasant and affecting odor from the liquid, and these “nocebo responders” experienced greater disgust when they were presented with disgusting images when the fluid was present. On fMRI, they also showed enhanced activation in the left orbitofrontal cortex, which sits above the eye sockets in the brain and has extensive connections with sensory areas and the limbic system structures that are involved in emotion and memory.
There’s another covert factor that can fuel the nocebo effect. In medical settings, “clinicians often impart negative expectations to patients without intending to,” Wager says. In fact, how information is presented when a patient is asked to give informed consent to a treatment can make them susceptible to the nocebo effect. When practitioners deliver negative verbal suggestions about an increase in pain during a procedure, for example, this can increase anticipatory anxiety in patients and trigger the activation of cholecystokinin (CCK), a hormone that facilitates nocebo-induced pain increases, Dr. Colloca explains
How to counter the nocebo effect
If you suspect that you’re susceptible to the nocebo effect, you don’t have to be at its mercy. There are ways of countering or controlling it, if you understand what’s really going on and take steps to temper your thoughts and expectations. Here’s how:
Know that what you’re feeling is real.
Reminding yourself that the nocebo effect is common can potentially quell your worries about how you’ll respond to a treatment. “Sometimes when people talk about the placebo or nocebo effect and symptoms that aren’t actually part of the drug or treatment, they tend to feel stupid,” Helfer says. “But this happens to everyone”—and it’s important to remember that. “You’re not imagining the symptoms—they’re real but they’re caused by your thoughts,” she adds. This may be an instance when using positive self-talk may help, Helfer says. By shifting your thoughts and expectations into the positive or neutral zone before taking a medicine or receiving a medical treatment, you may end up feeling better after you get it.
Learn about the nocebo effect.
Realizing that you could experience the nocebo effect is the first step toward managing it. In fact, if people learn about the nocebo effect, in addition to receiving standard information about a medication, it could dampen the nocebo effect, research suggests. A study from New Zealand found that when people were shown a video explaining the nocebo effect, a negative media report, or a control video before being given a bogus “mood-stabilizing drug,” the participants in the nocebo-explanation group reported significantly fewer side effects than people in either of the other groups did at the 48-hour follow-up.
Check your expectations.
If you remind yourself that your symptoms or response to a treatment could follow your negative expectations, that may help you guard against it, too. If you do experience symptoms shortly after taking a particular drug or getting a vaccine, Dr. Barsky recommends asking yourself what the likelihood is that it’s tied to your current situation. Have you had this same symptom before when you weren’t taking the medicine? The reality is, it can take two to 14 days for you to feel sick after being exposed to certain viruses. “Stop for a moment and question your symptoms so that you don’t get caught in a cycle of worry and anxiety,” Dr. Barsky advises. Also, “remember that you weren’t symptom-free in daily life before you started taking the medicine.” After all, the human body is noisy, he adds, even when it’s healthy.
Talk to your prescriber about common side effects.
Ask your doctor or pharmacist about how likely side effects are to occur. With medications, “the [package] inserts tend to mention every possible side effect under the sun,” Helfer says. “If you have a pharmacist you trust, ask: which ones am I likely to get? Information is your friend but a reality check is helpful to assess actual risk versus perceived or possible risk.” Research has found, for example, that the use of positive framing instead of negative framing of health-related messages—such as 70% of people who take this drug will not experience a headache from it, instead of 30% of people experience headaches from it—may reduce the occurrence of nocebo effects.“It’s important to reframe things that you see as scary in a positive way and make space for positive responses,” says Dr. Colloca.
Put yourself in a pleasant headspace.
There are benefits of creating associations between a medication and a positive sensory experience (like listening to a song you like) if you’re susceptible to the nocebo effect. “Distraction can be very helpful,” Dr. Barsky says. Similarly, a study involving 101 healthy participants found that inducing a positive mood—by watching a funny or upbeat video, for instance—can block the development of nocebo effects that stem from being provided with information about possible adverse effects. By entering an optimistic state, your mind stands a better chance of having a positive, instead of a negative, effect on how you feel.
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