As scientists, the placebo effect is something we learn about early on, even those of us that don’t do clinical research. Today I had the opportunity to attend a seminar discussing placebos in the context of clinical trials, presented by Mark W. Green, MD of Columbia University. Green offered a full review of placebo research, covering virtually all of the last century. However, amidst the placebo discussion, he mentioned something that I had never heard of before, the nocebo. According to the Medline Plus medical dictionary, a nocebo is a harmless substance that when taken by a patient is associated with harmful effects due to negative expectations or the psychological condition of the patient. It is sort of the antimatter of the placebo effect. If you condition someone to believe a treatment will have an adverse effect, it is likely the patient or subject will have an adverse response, independent of treatment.

In reading about the nocebo effect, I came across an article that suggests certain phrases commonly used in medical practice can generate negative feelings in a patient, conditioning them to a negative response. According to the article, words such as just and normally tend to elicit negative and somewhat paradoxical responses from the patient.

Just breathe normally.

I am breathing heavy just reading that.

Though this discussion may not have direct implications for us as bench scientists, Green’s presentation and my subsequent reading made me aware of the ultimate uncontrolled variable in clinical research, the subject. Thus, no matter how we control a study, single-, double- or triple-blind, the psychological effects of treatment, both placebo and nocebo, will always play into your findings.

Today I am thankful that yeast¹ don’t have a brain.

¹ The model system we use in my lab.