Placebo- and Nocebo-Effects in Cognitive Neuroenhancement: When Expectation Shapes Perception

Abstract

Objective: The number of students using prescription drugs to improve cognitive performance has increased within the last years. There is first evidence that the expectation to receive a performance-enhancing drug alone can result in improved perceived and actual cognitive performance, suggesting a substantial placebo effect. In addition, expecting a placebo can result in lower perceived and actual cognitive performance, suggesting a nocebo effect. Yet, the underlying mechanisms of these effects remain to be elucidated. The aim of our study was to investigate whether the expectation of receiving a performance-increasing drug or a performance-impairing drug leads to changes in actual and perceived cognitive performance, compared to a control group without expectation manipulation. Methods: A total of N = 75 healthy adults were recruited for an experiment to “try cognitive performance-modulating drugs.” A participant’s actual cognitive performance (alertness, working memory, sustained attention, and divided attention) using the standardized test of attentional performance (TAP) as well as their performance expectation were assessed. Participants were randomly assigned in equal numbers to either receiving a placebo performance increasing nasal spray (“Modafinil”) or a nocebo performance impairing nasal spray (“Vividrin ® ”) or no nasal spray (natural history). After placebo/nocebo nasal spray administration, cognitive performance was reassessed. Subsequent to the second assessment, participants rated their perceived change in cognitive performance, as well as adverse symptoms. Results: Unlike hypothesized, a positive or negative performance expectation did not result in changes in actual performance, corresponding to the induced expectation. Participants in the placebo-Modafinil group rated their perceived change in cognitive performance subsequent to the application of the nasal spray significantly better ( d = 1.16) compared to the nocebo-Vividrin ® group. Additionally, participants who expected to receive Modafinil felt less tired than participants in the Vividrin ® group ( d = 0.96). Conclusion: Manipulation of performance expectation affects the perceived change in performance and tiredness, but not the actual cognitive performance in healthy adults. This may explain why college students use such drugs despite their little impact on actual cognitive functioning.

Effects of open-label placebos on test performance and psychological well-being in healthy medical students: a randomized controlled trial

“…A recent study 46 (N = 58) showed that OLP reduced test anxiety but did not include test performance as an outcome variable. Previous studies using deceptive placebo treatments or manipulations of expectancy on objective outcome parameters of cognitive performance had yielded very mixed results 47 , 48 , suggesting that placebo effects on cognitive performance might be complex and dependent on a variety of factors. Our results suggest that the same applies to open-label application of placebos.…”

“…Interestingly, differential effects on subjective and objective outcome parameters has also been observed in traditional hidden placebo trials 15 , 49 as well as in OLP treatment of chronic back pain patients 18 . Winkler and Hermann 48 for instance have shown that a placebo, which was experimentally linked to either a positive (i.e., placebo-nootropic) or negative expectation (i.e., placebo-antihistamine agent), improved perceived but not actual cognitive performance in a standardized test.…”

Neuroenhancement in French and Romanian University Students, Motivations and Associated Factors

“…Munro et al cannot rule out the possibility that neuroenhancement prevented declines in academic performance, but conclude that students who engaged in neuroenhancement showed no increases in their academic performance and gained no detectable advantages over their peers [45]. Prescription drug consumption could affect neuroplasticity and may, therefore, result in deterioration of cognitive performance and even the personality of users [47].…”

“…Another type of risk regarding the safety of cognitive neuroenhancers is addiction. A nationwide survey estimates that almost one in twenty misusers of prescription drugs meet the criteria for dependence or abuse [47]. Physiological changes in the brain caused by repeated use could lead to increased use of these drugs in more demanding academic environments [48].…”

Prospective Evaluation of Changes in Pain Levels, Quality of Life and Functionality After Low Dose Radiotherapy for Epicondylitis, Plantar Fasciitis, and Finger Osteoarthritis

“…The statistical correlations between pain relief and functional outcomes across the disease entities in the current study are consistent with a relevant effect of LDRT. Although the study was uncontrolled, the lack of blinding is not expected to have had any significant impact on the objective functional tests (57).…”