Clinical trial on the effects of tramadol and paracetamol on physical cognitive and brain performance during cycling

Code: 17C09DL

The present proposal builds up on a previous project funded by the WADA entitled: Tramadol and sport: Effects on physical and sustained attention performance during cycling exercise. The aim of this project is to investigate further the effect of tramadol on cycling performance at the physical, cognitive and brain levels by: 1) addressing the potential moderator effect of physical fatigue; 2) testing the effect of the pain-killer on intense short anaerobic efforts (as final sprint); 3) studying the effect of the combination of tramadol and caffeine. This is particularly relevant as it appears from anecdotal reports that pro-cyclists are consuming a combination of the two drugs in order to improve performance.
The project consists of a placebo-controlled, double blind experiment. A single dose of 100mg of tramadol, 6mg/kg of caffeine, and the combination of both, versus placebo, will be administered to participants (in separate sessions). They will then complete a 40-min cycling submaximal exercise (at 60% VO2max). A 20-min indoor Time-Trial (TT) will follow this. Participants will complete a visual discrimination task while cycling both during the submaximal and TT tests. After that, participants will undertake three 30-sec Wingate tests. The Psychomotor Vigilance Task will be performed prior to and
after the exercise phase. Electroencephalography will be continuously recorded throughout the cycling exercise and at rest. We will also obtain measures of subjective performance such as perceived effort and mental fatigue. Subjects will complete the Profile of mood state questionnaire before and after every session.
We will investigate the effect of tramadol, paracetamol and the combination of both vs. placebo on physiological and subjective parameters related to cycling performance (at the physical, cognitive and brain levels) at constant load, during a self-paced indoor time trial and during short maximal intensity efforts.

Main Findings:

The use of tramadol, a weak opioid, is a controversial current topic of debate in cycling. However, little is known about is potnetial ergogonic and cognitive (harmful) effects. In this project, we aimed at providing novel empirical evidence on this issue. As control conditions we included placebo and paracetamol, the other mild analgesic commonly used in cylcing. A randomized, double-blind, placedbo-controlled trial (EudraCT number: 2018-000388-10) design study was performed. 20 participants completed a 40-min constant work-rate at 60% of the VO2max followed by a 20-min time trial (TT) on a cycle-ergometer after ingesting 100 mg tramadol, 1.5 g paracemtamol, or placebo (in seprate days/sessions). Participants completed the Psychomotor Vigilance Task (PVT) before substance administration and ten minutes before starting the warm-up, and the Sustained Attnetion to Response Task (SART) during the 60 min of exercise. Electroencephalography (EEG), heart rate (HR), and power output were recorded throughout the sessions. The rating of perceived effort (RPE; by means of he Borg scale) was measured at the end of the 40-min constant work-rate and the 20-min TT.

The PVT (baseline-corrected) results showed that participants were faster in the tramadol condition than in the paracetamol and placebo conditions. The average power output during the 20-min TT only revealed greater performance in the tramadol than in the paracetamol condition. Higher HR values were reported in the tramadol condition than in the paracetamol and placebo conditions. RPE findings evidenced lower values in hte tramadol condition than the other conditions in the 40-min constant work while no differences were observed in the 20-min TT. Cognitive performance in the SART did not differ between substances in the 20-min TT. During the 40-min constant work-rate, better accuracy was reported in the tramadol condition than in the placebo condition, accompanied by slower RT. The speed-accuracy trade off could be a sign of improved congitive control (i.e., better ability to inhibit unwanted responses at the expense of being slower). The analysis of EEG tonic spectral power revearled increased power in the tramadol condition than in the other conditions at rest, while no differences in EEG oscillatory activity (either tonic or event-related) were found during the exercise.

In sum, the results of this clinical trial sugest that neither tramadol nor paracetamol (vs. placebo) seem to improve exercise performance or impair the ability to stay focused during a pre-loaded 20-min TT.