The term nocebo effect refers to the harmful outcomes that result from people's negative beliefs, anticipations, or experiences related to the treatment rather than the pharmacological properties of the treatment. These outcomes may include a worsening of symptoms, a lack of expected improvement, or adverse events, and they may occur after the active treatment and the placebo that is supposed to imitate it. The nocebo effect is always unwanted and may distort estimates of treatment effectiveness and safety; moreover, it may cause discontinuation of therapy or withdrawal from a trial. The nocebo effect may be unintentionally evoked by the explanations given by healthcare professionals during a clinical consultation or consent procedures, or by information from other patients, the media, or the Internet.

The role of psychological mechanisms in the treatment process cannot be underestimated, the well-known placebo effect unquestionably being a factor in treatment. However, there is also a dark side to the impact of mental processes on health/illness as exemplified by the nocebo effect. This phenomenon includes the emergence or exacerbation of negative symptoms associated with the therapy, but arising as a result of the patient's expectations, rather than being an actual complication of treatment. The exact biological mechanisms of this process are not known, but cholecystokinergic and dopaminergic systems, changes in the HPA axis, and the endogenous secretion of opioids are thought to be involved. The nocebo effect can affect a significant proportion of people undergoing treatment, including cancer patients, leading in some cases to the cessation of potentially effective therapy, because of adverse effects that are not actually part of the biological effect of treatment. In extreme cases, as a result of suggestions and expectations, a paradoxical effect, biologically opposite to the mechanism of the action of the drug, may occur. In addition, the nocebo effect may significantly interfere with the results of clinical trials, being the cause of a significant proportion of complications reported. Knowledge of the phenomenon is thus necessary in order to facilitate its minimalization and thus improve the quality of life of patients and the effectiveness of treatment.

A growing body of evidence is emerging for a phenomenon known as the nocebo effect. This is when a person is conditioned to expect a negative response, or to anticipate negative effects from an experience. These findings highlight the importantance of effective communication with patients and the influence that good anxiety and pain management control can have in improving treatment outcomes. The placebo effect has been widely researched, but new studies have shown that nocebo can have a greater effect than placebo The nocebo effect is prevalent in interactions between patients and healthcare workers. Research has demonstrated that if a patient deems a healthcare professional not to understand or believe them, this can cause distress, and the physiological effect can reduce the prognosis of treatment. It has also been demonstrated that patients who are anxious or expect pain during a procedure, feel more pain because of this negative expectation.

The nocebo effect, the inverse of the placebo effect, is a well-established phenomenon, yet under-appreciated. It refers to nonpharmacological, harmful, or undesirable effects occurring after active or inactive therapy. The frequency of adverse events can dramatically increase by informing patients about the possible side effects of the treatment, and by negative expectations on the part of the patient. Patients who were told that they might experience sexual side effects after treatment with β-blocker drugs reported these symptoms between three and four times more often than patients in a control group who were not informed about these symptoms. Nocebo effect has been reported in several neurological diseases such as migraine, epilepsy, multiple sclerosis, Parkinson's disease and neuropathic pain, and in patients with depression. The investigation of the biological and theoretical underpinning of the nocebo phenomenon is at an early stage, and more research is required. Physicians need to be aware of the influence of nocebo phenomenon and be able to recognize it and minimize its effects.