The placebo effect's opponent is known as the nocebo effect. It portrays a scenario in which a bad result happens because someone thinks an intervention will be harmful. It is a phenomenon that the field of medication safety occasionally overlooks. Nocebo is a derivative of the Latin word for "to injure." Nocebo suggests that patients are more likely to encounter an unpleasant reaction to medication if they anticipate or are concerned about the adverse reaction. The negative effects are frequently clinically diagnosable and may be felt physically by the patient. The extreme negative impacts patients who were given a placebo during a clinical trial experienced are an illustration of the nocebo effect. Given that negative views are developed far more quickly than positive ones, some experts claim that the nocebo effect may have a greater impact on clinical outcomes than the placebo effect.

The nocebo effect might also have an impact on how patients react to generic drugs. When switching from an innovative "branded" product to a generic pharmaceutical, some patients may experience negative effects due to pre-existing cynicism about generic medications. It's crucial to keep in mind that nonverbal communication can sometimes cause a nocebo reaction. Nocebo effects seem to be more likely to occur in some patients. To prevent unintentionally starting the nocebo effect, women, people with anxiety or despair, people with a negative attitude, and people who are highly influenced by their environment may require extra attentive counseling. By achieving a proper balance between explaining both the beneficial and bad aspects of the treatment, as well as making sure the patient understands the treatment's logic, the danger of nocebo can be decreased.