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Exploring the potential synergistic pharmacological and psychological effects of caffeine on exercise performance: a placebo-balanced study

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Coso, Juan, Lara, Beatriz, Gallo-Salazar, César, Areces, Francisco, Aguilar-Navarro, Millán, Giráldez-Costas, Verónica, Gutiérrez-Hellín, Jorge, Valero, Fernando, Salinero, Juan Jose·2026·Biology of Sport
DOI 10.5114/biolsport.2026.153332PMC PMC12884890
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Abstract

Research specifically investigating the distinct pharmacological and expectancy effects of caffeine using the deceptive placebo-balanced design remains scarce and with contradictory results.The aim of this study was to investigate the potential synergy between the pharmacological and expectancy effects of caffeine on exercise performance by using a placebo-balanced design.Sixteen physically trained athletes (11 males and 5 females; 21.7 ± 5.0 yr) participated in a study with a deceptive protocol including four randomized conditions: placebo informed-placebo ingested (control); placebo informed-caffeine ingested (pharmacological effect); caffeine informed-placebo ingested (expectancy effect); and caffeine informed-caffeine ingested (combined effects).Sixty minutes after ingestion, participants performed a countermovement jump, a standing triple jump, a medicine ball throw and a 20-m running sprint test.Relative to control, the pharmacological effect trial increased standing triple jump distance (+2.1% p = 0.032; Cohen's d= 0.59) and reduced 20-m sprint time (-0.8% p = 0.030; Cohen's d= 0.60).The combined effect trial reduced 20-m sprint time (-0.8% p = 0.021; Cohen's d= 0.64) in comparison to control.The expectancy effect trial did not modify performance in any of the performance tests with respect to control.When averaging the performance across all four tests, improvements relative to the control trial were +0.9%, +0.6% and +1.3% for pharmacological, expectancy and combined effects, respectively.The ingestion of caffeine, whether or not participants expected to receive it, improved exercise performance.This suggests that the primary driver of caffeine's ergogenic effect is its pharmacological action, with only a minor contribution from expectancy.

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FIG. 1 Theoretical approach to the ergogenic effect of caffeine in sport. When caffeine is ingested in a real sporting context, the performance benefits may be derived from the pharmacological effects of the substance (such as the blockade of adenosine receptors) added to the psychological effects derived from the expectancy of ingesting an ergogenic aid (such as anticipated increased performance or reduced fatigue). Although in the real sporting context both potential effects are obtained together, the use of a placebo-balanced study, with a deceptive protocol, may help to isolate the pharmacological and expectancy effects to assess the total performance benefit derived from caffeine intake. Through the combination of ingestion of an active (caffeine) and a non-active (placebo) substances and after receiving true or deceived information about the substance ingested, the pharmacological effect (i.e., participant receives caffeine but is informed that has ingested a placebo), the placebo effect (i.e., the participant receives a placebo but is informed that has ingested caffeine) and the combined effect of caffeine intake (i.e., the participant receives caffeine and is informed that has received caffeine) can be obtained by comparison with a baseline situation (i.e., the participant receives placebo and is informed that has received a placebo).
FIG. 1 Theoretical approach to the ergogenic effect of caffeine in sport. When caffeine is ingested in a real sporting context, the performance benefits may be derived from the pharmacological effects of the substance (such as the blockade of adenosine receptors) added to the psychological effects derived from the expectancy of ingesting an ergogenic aid (such as anticipated increased performance or reduced fatigue). Although in the real sporting context both potential effects are obtained together, the use of a placebo-balanced study, with a deceptive protocol, may help to isolate the pharmacological and expectancy effects to assess the total performance benefit derived from caffeine intake. Through the combination of ingestion of an active (caffeine) and a non-active (placebo) substances and after receiving true or deceived information about the substance ingested, the pharmacological effect (i.e., participant receives caffeine but is informed that has ingested a placebo), the placebo effect (i.e., the participant receives a placebo but is informed that has ingested caffeine) and the combined effect of caffeine intake (i.e., the participant receives caffeine and is informed that has received caffeine) can be obtained by comparison with a baseline situation (i.e., the participant receives placebo and is informed that has received a placebo).CC BY · PubMed Central
FIG. 2 Jump height in a countermovement jump (CMJ), distances reached in a standing triple jump and a medicine ball throw and time to complete a 20-m sprint test in a placebo-balanced study with a deceptive protocol including four randomized conditions: 1) placebo informed–placebo ingested (control condition); 2) placebo informed–caffeine ingested (pharmacological effect); 3) caffeine informed–placebo ingested (expectancy effect); and 4) caffeine informed–caffeine ingested (combined effect). * depicts a statistical difference with respect to control, at p < 0.050. † depicts a statistical difference with respect to expectancy condition, at p < 0.050.
FIG. 2 Jump height in a countermovement jump (CMJ), distances reached in a standing triple jump and a medicine ball throw and time to complete a 20-m sprint test in a placebo-balanced study with a deceptive protocol including four randomized conditions: 1) placebo informed–placebo ingested (control condition); 2) placebo informed–caffeine ingested (pharmacological effect); 3) caffeine informed–placebo ingested (expectancy effect); and 4) caffeine informed–caffeine ingested (combined effect). * depicts a statistical difference with respect to control, at p < 0.050. † depicts a statistical difference with respect to expectancy condition, at p < 0.050.CC BY · PubMed Central
FIG. 3 Side effects in a placebo-balanced study with a deceptive protocol including four randomized conditions: 1) placebo informed– placebo ingested (control condition); 2) placebo informed–caffeine ingested (pharmacological effect); 3) caffeine informed–placebo ingested (expectancy effect); and 4) caffeine informed–caffeine ingested (combined effect). * depicts a statistical difference with respect to control, at p < 0.050.
FIG. 3 Side effects in a placebo-balanced study with a deceptive protocol including four randomized conditions: 1) placebo informed– placebo ingested (control condition); 2) placebo informed–caffeine ingested (pharmacological effect); 3) caffeine informed–placebo ingested (expectancy effect); and 4) caffeine informed–caffeine ingested (combined effect). * depicts a statistical difference with respect to control, at p < 0.050.CC BY · PubMed Central
FIG. 4 Overall performance benefits and side effects in a placebobalanced study with a deceptive protocol including four randomized conditions: 1) placebo informed–placebo ingested (control condition); 2) placebo informed–caffeine ingested (pharmacological effect); 3) caffeine informed–placebo ingested (expectancy effect); and 4) caffeine informed–caffeine ingested (combined effect). The performance benefit represents the average of the changes produced by each condition over control (baseline) when analysing the data of 4 performance tests (countermovement jump, standing triple jump, medicine ball throw and 20-m sprint test). The side effect represents the average of the changes produced by each condition over control (baseline) when analysing the data of 8 side effects (nervousness, energy, irritability, muscle pain, headache, stomachache, diuresis and insomnia).
FIG. 4 Overall performance benefits and side effects in a placebobalanced study with a deceptive protocol including four randomized conditions: 1) placebo informed–placebo ingested (control condition); 2) placebo informed–caffeine ingested (pharmacological effect); 3) caffeine informed–placebo ingested (expectancy effect); and 4) caffeine informed–caffeine ingested (combined effect). The performance benefit represents the average of the changes produced by each condition over control (baseline) when analysing the data of 4 performance tests (countermovement jump, standing triple jump, medicine ball throw and 20-m sprint test). The side effect represents the average of the changes produced by each condition over control (baseline) when analysing the data of 8 side effects (nervousness, energy, irritability, muscle pain, headache, stomachache, diuresis and insomnia).CC BY · PubMed Central

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Research works printed but not linked: 2

  1. [2]Beedie C, Hettinga F. Introduction to the special edition on the placebo effect in sport and exercise. Eur J Sport Sci. 2020; 20(3): 277– 8. doi: 10.1080/17461391.2020.1757682. 32299310 · DOI
  2. [23]Bühler E, Lachenmeier DW, Schlegel K, Winkler G. Development of a tool to assess the caffeine intake among teenagers and young adults. Ernähr Umsch. 2014; 61(4): 58– 63.

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Metadata

Authors
Coso, J., Lara, B., Gallo-Salazar, C., Areces, F., Aguilar-Navarro, M., Giráldez-Costas, V., Gutiérrez-Hellín, J., Valero, F., & Salinero, J. J.
Affiliations
  • Universidad Rey Juan Carlos (ES)
  • HM Hospitales (ES)
  • University of Castilla-La Mancha (ES)
ORCID
Venue
Biology of Sport
Publisher
Termedia Sp. z.o.o.
Published
2026
Volume
43
Pages
95-105
ISSN
0860-021X (ISSN-L)
DOI
10.5114/biolsport.2026.153332
PMC
PMC12884890
OpenAlex
W4412997432
Cited by
3
References
0
Citations by year
2026: 3
FWCI
1.70
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Biology of Sport (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • RUIdeRA - Institutional University Repository (University of Castilla-La Mancha) (submittedVersion, other-oa)
Funders
  • Ministerio de Ciencia e Innovación (.13039/501100011033, / AEI/10, 501100011033, PID2020)
  • Agencia Estatal de Investigación (501100011033, 13039, .13039/501100011033, AEI/10)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
  • Social Sciences › Psychology › Developmental and Educational Psychology › Sport Psychology and Performance
Keywords
caffeine, exercise performance, placebo effect, expectancy effects, pharmacological activity, ergogenic aids, countermovement jump, medicine ball throw, sprint performance, athletes

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