Distinguishing caffeine expectancy from pharmacological effects: a comparative review of experimental designs with future directions

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Caffeine (CAF) is among the most widely consumed bioactive substances and is recognized for its ergogenic benefits. Yet, separating its expectancy-driven effects from pharmacological effects remains challenging. This review compares the randomized double-blind placebo-controlled crossover, deceptive placebo-balanced, and double-deceptive placebo-balanced crossover designs commonly used in CAF studies. While the double-blind crossover design effectively controls individual variability, it cannot directly measure expectancy. In contrast, placebo-balanced crossover designs incorporating deception provide the most comprehensive framework when the aim is to separate pharmacological and expectancy-related effects, allowing a more precise interpretation of caffeine's mechanisms. Differences in studies designs may partially explain inconsistencies in the literature, as expectancy-related components are not equally controlled across experimental approaches.

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