A wife’s playful prank on her husband has inadvertently demonstrated how easily negative expectations can make a person feel genuinely ill. Science writer Helen Pilcher recently recounted how, after giving her husband a monthly beer subscription for his birthday, she told him the brewery had issued a contamination recall. Within moments, her husband reported feeling sick. There was, of course, no recall – simply a mischievous experiment to test a phenomenon that Pilcher has spent years studying.
The Nocebo Effect Explained
Pilcher is the author of This Book May Cause Side Effects, an exploration of the nocebo effect – the so-called “evil twin” of the placebo effect. Derived from the Latin nocere (to harm), the nocebo effect occurs when negative expectations about health produce genuine negative symptoms. While placebos show how positive beliefs can improve outcomes, nocebos reveal the reverse: a few carefully chosen words can conjure real pain, nausea or fatigue.
“Sometimes, all it takes to make someone feel genuinely unwell is a few carefully chosen words,” Pilcher writes. The phenomenon can create, exacerbate and prolong symptoms, and when those symptoms coalesce, people become ill – not from disease, but from the intimate relationship between mind and body. Some experts believe the nocebo effect may have an even greater impact than the placebo effect, because negative perceptions can form more rapidly than positive ones.
Scientific Evidence of the Nocebo Effect
The effect is not merely anecdotal. A substantial body of peer-reviewed research confirms that negative expectations can drive measurable physiological changes. In one study, patients who had just undergone minor keyhole surgery received a harmless saline infusion. They were told the infusion would temporarily increase their pain – and it did exactly that.
In another experiment, 40 asthmatic adults inhaled water vapour from an inhaler they believed contained an irritant. Nineteen reported feeling wheezy, and 12 suffered a full-blown asthma attack. The inhaler contained only water.
The nocebo effect also distorts outcomes in real-world medicine. A meta-analysis of 12 clinical trials involving more than 45,000 participants, published during the pandemic, found that 76% of all common adverse reactions to COVID-19 vaccines could be attributed to the nocebo effect. Many participants who received placebo shots reported side effects identical to those reported by vaccinated individuals. A separate review put the figure at 72% after the first dose and 52% after the second.
Prescription medications are similarly affected. Studies show that a significant proportion of side effects from statins – cholesterol-lowering drugs – are not caused by the drugs themselves but by the nocebo effect. For beta-blockers, patients who were warned about potential sexual side effects were three to four times more likely to report them than those who were not warned. And in gluten sensitivity, researchers have found that people who believe they are intolerant can develop gastrointestinal symptoms after consuming a harmless substance they think contains gluten. When blinded to their diet, some can eat regular bread without incident.
Pilcher points to the work of Harvard psychologist Ellen Langer, who demonstrated that the perception of time can alter blood sugar levels. People with diabetes were made to sit in front of a clock running at double, regular or half speed. Their blood glucose levels rose and fell with the perceived passing of time, not the actual passing of time.
Alia Crum at Stanford conducted a now-famous milkshake study. Participants drank identical milkshakes labelled either “high-calorie” or “diet”. Levels of the “hunger hormone” ghrelin dropped three times faster after consuming the drink they believed would make them fuller faster – purely because of their mindset.
Animal studies have mapped the biological chain of events linking brain activity to physical effects. Asya Rolls at the Technion-Israel Institute of Technology and her colleagues showed that activating specific brain areas in mice triggers changes in the immune system. These changes can speed recovery from heart attacks or slow the growth of cancer. Writing in Nature Communications, the researchers stated: “These findings introduce a physiological mechanism whereby the patient’s psychological state can impact anti-tumour immunity and cancer progression.” They emphasise that negative thinking does not cause cancer, nor does positive thinking cure it – but the link between neural activity and disease deserves further exploration.
Arthur Barsky, a professor of psychiatry who has extensively studied medically unexplained symptoms, has noted that a significant proportion of reported adverse drug effects may be attributable to nocebo responses. Neurobiological research has identified pathways such as the cholecystokinin (CCK) system that mediate the effect, though more work is needed to understand individual variability.
Societal Impact and the Role of Social Media
The nocebo effect does not stop at the individual level. It can spread through populations like a virus, driving seemingly inexplicable “mystery illnesses”. Historical examples include the dancing plagues of the Middle Ages and “hex deaths”, where individuals died after believing they were cursed. In the modern era, the phenomenon has been linked to Havana syndrome – the intense symptoms of headaches, dizziness and nausea reported by US diplomats who believed they had been struck by an unidentified weapon. Some researchers propose that the fear of an anticipated attack triggered the symptoms, though alternative theories such as pulsed microwave radiation are also being investigated.
During the pandemic, the nocebo effect contributed to an outbreak of tics among young people, particularly teenage girls, who watched videos of tic-like movements on TikTok. The condition became known as “TikTok tics” and is considered a form of sociogenic illness or functional neurological disorder, where the brain imitates observed behaviours.
Pilcher argues that social media is now “turbocharging” the spread of nocebo-generated symptoms. She also believes the effect is responsible for a significant proportion of “medically unexplained symptoms” – sensations such as pain, fatigue and dizziness that have no discernible organic cause. Sufferers have historically been labelled hypochondriacs, a term the medical profession has rightly discarded because it implies suffering is feigned or exaggerated.
“This view is categorically wrong,” Pilcher writes. The nocebo effect generates real symptoms, backed by detailed evidence that neural activity can precipitate physical change.
The philosophical roots of this blind spot lie in Cartesian dualism – the 17th-century idea, proposed by René Descartes, that mind and body are separate, non-interacting entities. That dogma shaped the modern medical model, which still defaults to the premise that physical symptoms must have physical roots. But as the work of Rolls, Langer, Crum and others demonstrates, the boundary is far more permeable. Understanding the nocebo effect – underestimated and overlooked – is essential, Pilcher argues, for anyone who wants to understand the many ways they can become ill.