Can the Brain Trick You Into Feeling Sick?

You read the leaflet that comes with a new medicine. Possible side effects: headache, nausea, tiredness. The next day you have a headache. Was it the medicine, or did reading the list make you more likely to feel it?

The question sounds like it is asking whether symptoms are “real.” It is not. Pain, nausea and fatigue are produced by the brain in every case, whether the trigger is an infection, a drug or an expectation. What researchers have found is that the brain’s predictions about the body can strongly shape what the body feels.

The flip side of the placebo effect

Most people have heard of the placebo effect, when an inactive treatment makes people feel better. Its opposite is the nocebo effect, a phenomenon whereby expectations of symptom worsening play a crucial role.

A classic experiment shows that nocebo effects involve measurable biology. Healthy volunteers experienced experimentally induced arm pain, and some were told the pain would get worse. That verbal suggestion led to increased pain, which was associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the body’s main hormonal stress system. The anti-anxiety drug diazepam antagonized both the extra pain and the HPA hyperactivity, suggesting that anxiety played a major role. Another drug, proglumide, which blocks receptors for a brain chemical called cholecystokinin (CCK), blocked the nocebo pain increase completely but had no effect on HPA hyperactivity. Neither drug relieved ordinary pain; they acted only on the nocebo-induced pain increase. The authors proposed that placebo and nocebo effects may involve the opposite activation of endogenous opioid and CCK systems, the brain’s own pain-dampening and pain-amplifying chemistry.

In other words, an expectation did not just change what people said about their pain. It seemed to change chemical signaling in a way that a specific drug could block.

Nocebo responses outside the lab

Clinical trials offer a natural test, because some participants receive a placebo. A meta-analysis of COVID-19 vaccine trials included 45,380 participants. After the first dose, 35.2% of placebo recipients experienced systemic adverse events, most often headache (19.3%) and fatigue (16.7%). Comparing the two arms, the authors estimated that nocebo responses accounted for 76.0% of systemic adverse events after the first dose and 51.8% after the second. Vaccine recipients still reported significantly more adverse events, so the vaccines did cause some side effects. The authors also note that such placebo-arm symptoms are thought to come from a mix of misattribution of routine background symptoms, anxiety, and expectations, so not every symptom in a placebo group is a nocebo effect in the strict sense. They also flag a relatively small number of trials and high heterogeneity.

Another striking example involves statins, common cholesterol-lowering drugs. In a UK trial, 200 participants who had stopped or were considering stopping statins because of muscle symptoms went through six double-blinded two-month periods of either a statin or a placebo. Overall, no difference in muscle symptom scores was found between the statin and placebo periods. Withdrawals because of intolerable muscle symptoms were 9% during a statin period and 7% during a placebo period. This is a group-level result. It does not mean that no one ever has muscle side effects from statins, only that, on average in this group, the symptoms were about as common on placebo.

Across the wider literature, an umbrella review of 372 studies with 158,312 participants found that the magnitude of nocebo effects ranged from 0.32 to 0.90 on a standardized scale, depending on the study.

When the brain’s predictions go wrong

Nocebo effects are usually temporary. But some people develop persistent symptoms that are also shaped by how the brain processes signals from the body. One example is functional neurological disorder (FND), which can cause problems such as seizures, abnormal movements or dizziness.

Symptoms of this broad kind are common in neurology. In a study of 3,781 new patients referred to neurology clinics in Scotland, the combined category of functional and psychological symptoms (16%) was the second most common diagnosis after headache. That category is wider than FND alone. A 2022 review describes FND as common in neurological practice and emphasizes that diagnosis rests on recognizable patterns of genuinely experienced symptoms and signs. It also notes that psychological stressors are common risk factors, but are often absent, so FND cannot simply be dismissed as stress.

What might be happening in the brain? The same review lists overactivity of the limbic system, the development of an internal symptom model as part of a predictive coding framework, and dysfunction of brain networks that gives movement the sense of voluntariness. The predictive idea has been developed in detail in a theoretical paper. It proposes that the brain constantly combines prior expectations with incoming sensory evidence, and that symptoms can arise when a percept or belief is held with undue certainty following attention focused on the body. The model aims to explain why such symptoms are shaped by attention, expectation, prior experience and cultural beliefs while still being involuntary. It is a hypothesis, not a proven mechanism, but it offers a way to understand symptoms that are neither imagined nor caused by damaged tissue.

What is still uncertain

Measuring a nocebo effect is harder than it looks. Placebo groups pick up symptoms that would have happened anyway, and people may notice and report everyday aches more when they are watching for them. Many lab studies use mild pain in healthy volunteers, which may not reflect what patients experience. For FND, the proposed mechanisms and predictive models are promising, but researchers are still working out how the different mechanisms fit together and why some people are affected and others are not.

The takeaway

Yes, in a sense the brain can make you feel sick, but “trick” can be misleading. Expectations, attention and anxiety appear to change how the brain processes signals from the body, sometimes through specific chemical pathways, and the resulting symptoms are real experiences, not fakes. Understanding this can help explain why the same pill or injection can feel so different to different people. Functional disorders can be treated, and the 2022 review notes that evidence supports tailored multidisciplinary treatment that can involve physical and psychological therapy. If you have symptoms that worry you, persist or affect daily life, please see a doctor or other qualified health professional, who can look for causes and suggest the right care. Never stop a prescribed medicine without talking to your doctor first.