Objectives: To investigate the effect of tramadol on performance during a 20-min cycling time-trial (Exper- iment 1), and to test whether sustained attention would be impaired during cycling after tramadol intake (Experiment 2). Design: Randomized, double-blind, placebo controlled trial. Methods: In Experiment 1, participants completed a cycling time-trial, 120-min after they ingested either tramadol or placebo. In Experiment 2, participants performed a visual oddball task during the time-trial. Electroencephalography measures (EEG) were recorded throughout the session. Results: In Experiment 1, average time-trial power output was higher in the tramadol vs. placebo condition (tramadol: 220 W vs. placebo: 209 W; p < 0.01). In Experiment 2, no differences between conditions were observed in the average power output (tramadol: 234 W vs. placebo: 230 W; p > 0.05). No behavioural differences were found between conditions in the oddball task. Crucially, the time frequency analysis in Experiment 2 revealed an overall lower target-locked power in the beta-band (p < 0.01), and higher alpha suppression (p < 0.01) in the tramadol vs. placebo condition. At baseline, EEG power spectrum was higher under tramadol than under placebo in Experiment 1 while the reverse was true for Experiment 2. Conclusions: Tramadol improved cycling power output in Experiment 1, but not in Experiment 2, which may be due to the simultaneous performance of a cognitive task. Interestingly enough, the EEG data in Experiment 2 pointed to an impact of tramadol on stimulus processing related to sustained attention. Trial registration: EudraCT number: 2015-005056-96.

This project was supported by grants from the World Anti- doping Agency (WADA) (REF:15C01DS) to Daniel Sanabria, Mikel Zabala, James Hopker, Darías Holgado and Thomas Zandonai, from the Spanish Ministerio de Economía, Industria y Competitividad- PSI2016-75956-P- to Daniel Sanabria and Mikel Zabala, a predoc- toral grant from the Spanish Ministerio de Economía, Industria y Competitividad (BES-2014-069050) to Luis Ciria, and a Span- ish "Ministerio de Educación, Cultura y Deporte" predoctoral grant (FPU14/06229) to Darías Holgado.