The “nocebo effect” is like the placebo effect, except in reverse. Whereas placebos trick people into feeling better, “nocebos” are things that make people feel worse, even though they don’t really exist. They can even kill people! Here’s how we can trick ourselves into dying, and how doctors may have found a cure.

The Nocebo Effect

Let’s begin with a story. A young man who had been in treatment for depression for some time hit a low point after his girlfriend left him. He took an entire bottle of his medication. As soon as he finished the bottle, he realized he’d made a mistake. At the hospital, grievously ill, he lingered near death. He couldn’t breathe. His blood pressure was dangerously low. After making inquiries, the doctors found out that he had been in a study for a new antidepressant. That might explain why none of the tests they ran on him was able to indicate what drug was poisoning him. They contacted the doctors coordinating the study.

The man had been given placebos. The placebos had worked, improving his mood and making him sure that he’d been given the active medication. When he overdosed on the sugar pills, the placebo effect he’d been experiencing transitioned into the “nocebo effect.” Convinced he was dying, he actually began to die. Once he was told he was in no danger, he recovered.

Not all people do. There are numerous comical instances of the nocebo effect in which people are given what they believe is an emetic and begin to throw up, only to discover that the emetic was saline. Huge swathes of the population rush to the hospital whenever a new virus gets reported on the news. Some secret societies even took advantage of the nocebo effect; they would blindfold their initiates and either run the back of a knife along their skin or cut them very slightly, then pour warm water over the cut, making them feel like they were bleeding profusely and scaring the hell out of them.

In the wrong situation, the nocebo effect can be extremely dangerous. People who expect to die going into surgery are more likely to have delayed recovery and serious complications. At least one man seems to have died of a metastasized tumor that didn’t metastasize. He was told he had a given number of months to live, and lived only that long. The autopsy revealed that he wasn’t in any danger from the small and isolated tumor they found on his liver. He’d just died.

Why Your Doctor Talks Like That

The nocebo effect and the attempts made to avoid it help explain the exaggeratedly bland hospital language that often exasperates patients. “This is going to hurt like hell,” seems charmingly honest, but it’s also something that can cause people to hurt more than they would for the comparatively disingenuous “some patients may experience some discomfort.”

A few words are effective in causing or preventing pain. Patients with back pain who took a stretch test were more likely to feel pain if the doctors administering it admitted it could hurt. If the doctors just shut up and let them stretch, they tended to report no pain.

This puts doctors in a bind. There’s no ethical way to practice medicine without allowing patients informed consent. Informed consent means letting a patient know about everything that could go wrong with them. By mentioning these details, all the things that could cause a patient to feel pain, to regress, or to die, a doctor could be increasing the suffering, or even hastening the death, of a person who would have been fine with less information. This puts doctors in the position of trying to give patients information while simultaneously trying to keep them from focusing on it. The practice leads to some weird quirks. One paper on the nocebo effect and surgery notes “an epidemic that “kills 1,286 people out of every 10,000” is perceived as worse than an epidemic that “kills 24.14% of the population,” even though the latter kills almost twice as many people.” It advises doctors to give death and complication rates in percentages, rather than numbers per thousand.

The Cure for the Non-Existent

Experiments designed to study the nocebo effect are few and far between, as most doctors are loathe to try to create illness in their patients. But there is some hope for those who don’t think they can best their own brain in a battle of wills. The nocebo effect seems to follow a specific pathway in the brain, and that pathway can be blocked.

Cholecystokinin (cck) is a hormone found in the gut and in the brain. In the gut cck and its variants regulate the release of bile and other digestive enzymes. In the brain, it’s a little different — two versions of it cholecystokinin, cck-a and cck-b, both bind to receptors that dial down the dopamine in the brain when activated. This dials up the level of depression and anxiety that a person feels. Increased relaxation and happiness decrease pain. Increased anxiety and depression alert people to pain, and help them focus on it. When injected with something that temporarily takes out the cck receptors, the nocebo effect lessens, and people have better outcomes.

Which makes me want a meta-experiment. What if people are told they are being injected with something that takes out the nocebo effect, but it’s actually a placebo? What will happen to patients in the battle of the ‘cebos?

Top Image: Tom Varco Second Image: D Coatzee Doctor Image: Seattle Municipal Archives.

[Sources: What is the Nocebo EffectNothing, Nocebo Phenomena in MedicineFraming for Success: Nocebo Effects in Thoracic SurgeryThe Placebo: A ReaderThe Biochemical and Neuroendocrine Bases of the Nocebo Effect.]


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