Placebo Effects and Physical Performance: Central and Peripheral Mechanisms Investigated by Different Experimental Designs

Classical randomized clinical trial (RCT) controlled by a placebo is considered as the gold-standard design when evaluating the efficacy of drugs and interventions, as a given treatment is scientifically sound only if it is superior to placebo. One of strongest threats to placebo is that a double-blinded RCT could not completely neutralize every human consciousness-distorted reality; behavioral aspects such as the belief on a given treatment may directly result in different placebo effects and produce different treatment placebo effect sizes. Any patient may create his/her own expectation on a situation having a chance of 50% placebo vs 50% treatment depending on the available information; beliefs may impact on working mechanism of pharmacological treatments, but also on placebos. One alternative emerged from debates by different scientific fields; the control for the participant's expectancy by using an active substance-perceived placebo. When compared to a traditional double-blinded placebo-controlled RCT design, the placebo-deceived design has the advantage of controlling expectation and anxiety biases in treatments having combined pharmacological and psychological effects, despite some obvious limitation.

Mechanisms underpinning the ergogenic effect of placebos are unclear, but the suggestion is that the expectancy in using an ergogenic treatment/substance leads to psychobiological changes comparable to the actual treatment. A question that arises over RCT designs is how much effect on physical performance can be attributed to the actual substance and how much to the expectancy of receiving the actual substance. This question is relevant, as clinical and exercise settings have used double-blinded placebo-controlled RCT designs to investigate the ergogenic aids effects and mechanisms. However, participants may experience different placebo effect sizes in a double-blinded RCT design. This study will investigate ergogenic placebo effects and mechanisms elicited by double-blinded placebo-controlled RCT and deceived-placebo designs.

This crossover study will investigate two different experimental designs. During the traditional double-blind RCT, participants will be informed that they will be randomly assigned to caffeine and placebo sessions, thereby having 50% placebo chances vs 50% caffeine chances. However, they will receive placebo capsules in both RCT sessions (non-informed substance/received placebo). In contrast, they will be precisely informed about their allocation (either caffeine or placebo trial) in the deceived-placebo design, however they will ingest placebo capsules in both sessions (informed caffeine/received placebo vs informed placebo/received placebo), thereby controlling caffeine pharmacological effects. A true caffeine trial (informed caffeine/received caffeine 6 mg·kg-1) will be performed as a positive control in the last session.