Predicting the ergogenic response to methylphenidate



Methylphenidate (MPH) and other stimulants have been shown to enhance physical performance. However, stimulant research has almost exclusively been conducted in young, active persons with a normal BMI, and may not generalize to other groups. The purpose of this study was to determine whether the ergogenic response to MPH could be predicted by individual level characteristics.


We investigated whether weekly minutes of moderate-to-vigorous physical activity (MVPA), age, and BMI could predict the ergogenic response to MPH. In a double-blind, cross-over design 29 subjects (14M, 15F, 29.7 ± 9.68 years, BMI: 26.1 ± 6.82, MVPA: 568.8 ± 705.6 min) ingested MPH or placebo before performing a handgrip task. Percent change in mean force between placebo and MPH conditions was used to evaluate the extent of the ergogenic response.


Mean force was significantly higher in MPH conditions [6.39% increase, T(25) = 3.09, p = 0.005 118.8 ± 37.96 (± SD) vs. 111.8 ± 34.99 Ns] but variable (coefficient of variation:163%). Using linear regression, we observed that min MVPA (T(25) = −2.15, β = −0.400, p = 0.044) and age [T(25) = −3.29, β = −0.598, p = 0.003] but not BMI [T(25) = 1.67, β = 0.320 p = 0.109] significantly predicted percent change in mean force in MPH conditions.


We report that lower levels of physical activity and younger age predict an improved ergogenic response to MPH and that this may be explained by differences in dopaminergic function. This study illustrates that the ergogenic response to MPH is partly dependent on individual differences such as habitual levels of physical activity and age.

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  1. Amorim P, Lecrubier Y, Weiller E et al (1998) DSM-IH-R psychotic disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI. Eur Psychiatry 13:26–34.

  2. Briegleb SK, Gulley JM, Hoover BR, Zahniser NR (2004) Individual differences in cocaine- and amphetamine-induced activation of male Sprague–Dawley rats: contribution of the dopamine transporter. Neuropsychopharmacology 29:2168–2179.

  3. Bull FC, Maslin TS, Armstrong T (2009) Global physical activity questionnaire (GPAQ): nine country reliability and validity study. J Phys Act Health 6:790–804

  4. Connell CJW, Thompson B, Turuwhenua J et al (2017) Effects of dopamine and norepinephrine on exercise-induced oculomotor fatigue. Med Sci Sports Exerc 49:1778–1788.

  5. Dang LC, Samanez-Larkin GR, Castrellon JJ et al (2016) Associations between dopamine D2 receptor availability and BMI depend on age. NeuroImage 138:176–183.

  6. Doherty M, Smith PM (2005) Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis. Scand J Med Sci Sports 15:69–78.

  7. Dwyer G, Davis S (2017) ACSM’s. In: Health related physical fitness assessment manual, 3rd edn. Lippincott Williams & Wilkings, Philadelphia, pp 3–7 2008.

  8. Ebada ME, Kendall DA, Pardon M-C (2016) Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice. Behav Brain Res 311:228–238.

  9. Eisenmann JC, Wickel EE (2007) Estimated energy expenditure and physical activity patterns of adolescent distance runners. Int J Sport Nutr Exerc Metab 17:178–188

  10. Ekkekakis P, Lind E (2005) Exercise does not feel the same when you are overweight: the impact of self-selected and imposed intensity on affect and exertion. Int J Obes Relat Metab Disord 30:652–660.

  11. Ekkekakis P, Hall EE, Petruzzello SJ (2005) Variation and homogeneity in affective responses to physical activity of varying intensities: an alternative perspective on dose–response based on evolutionary considerations. J of Sport Sci 23:477–500.

  12. Erixon-Lindroth N, Farde L, Wahlin T-BR et al (2005) The role of the striatal dopamine transporter in cognitive aging. Psychiatr Res Neuroimage 138:1–12.

  13. Goldman-Rakic PS, Brown RM (1981) Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 6:177–187.

  14. Hasegawa H, Piacentini MF, Sarre S et al (2008) Influence of brain catecholamines on the development of fatigue in exercising rats in the heat. J Physiol 586:141–149.

  15. Heyes MP, Garnett ES, Coates G (1985) Central dopaminergic activity influences rats ability to exercise. Life Sci 36:671–677

  16. Hilty L, Jäncke L, Luechinger R et al (2010) Limitation of physical performance in a muscle fatiguing handgrip exercise is mediated by thalamo-insular activity. Hum Brain Mapp 32:2151–2160.

  17. Horstmann A, Fenske WK, Hankir MK (2015) Argument for a non-linear relationship between severity of human obesity and dopaminergic tone. Obes Rev 16:821–830.

  18. Kimko HC, Cross JT, Abernethy DR (1999) Pharmacokinetics and clinical effectiveness of methylphenidate. Clin Pharmacokinet 37:457–470.

  19. King M, Rauch LHG, Brooks SJ et al (2017) Methylphenidate enhances grip force and alters brain connectivity. Med Sci Sports Exerc 49:1443–1451.

  20. Klass M, Roelands B, Lévénez M et al (2012) Effects of noradrenaline and dopamine on supraspinal fatigue in well-trained men. Med Sci Sports Exerc 44:2299–2308.

  21. Knab AM, Lightfoot JT (2010) Does the difference between physically active and couch potato lie in the dopamine system? Int J Biol Sci 6:133–150

  22. Li S-C, Rieckmann A (2014) Neuromodulation and aging: implications of aging neuronal gain control on cognition. Curr Opin Neurobiol 29:148–158.

  23. Marcora SM (2016) Can doping be a good thing? Using psychoactive drugs to facilitate physical activity behaviour. Sports Med 46:1–5.

  24. Mathes WF, Nehrenberg DL, Gordon R et al (2010) Dopaminergic dysregulation in mice selectively bred for excessive exercise or obesity. Behav Brain Res 210:155–163.

  25. Meeusen R, De Meirleir K (1995) Exercise and brain neurotransmission. Sports Med 20:160–188.

  26. Meeusen R, Roelands B (2010) Central fatigue and neurotransmitters, can thermoregulation be manipulated? Scand J Med Sci Sports 20 Suppl 3:19–28.

  27. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113.

  28. Pan D, Gatley SJ, Dewey SL et al (1994) Binding of bromine-substituted analogs of methylphenidate to monoamine transporters. Eur J Pharmacol 264:177–182.

  29. Piacentini MF, Meeusen R, Buyse L et al (2002a) No effect of a selective serotonergic/noradrenergic reuptake inhibitor on endurance performance. Eur J Sport Sci 2:1–10.

  30. Piacentini MF, Meeusen R, Buyse L et al (2002b) No effect of a noradrenergic reuptake inhibitor on performance in trained cyclists. Med Sci Sports Exerc 34:1189–1193

  31. Rauch HGL, Schönbächler G, Noakes TD (2013) Neural correlates of motor vigour and motor urgency during exercise. Sports Med 43:227–241.

  32. Rhodes JS, Garland T (2003) Differential sensitivity to acute administration of Ritalin, apomorphine, SCH 23390, but not raclopride in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology 167:242–250.

  33. Rhodes JS, Hosack GR, Girard I et al (2001) Differential sensitivity to acute administration of cocaine, GBR 12909, and fluoxetine in mice selectively bred for hyperactive wheel-running behavior. Psychopharmacology 158:120–131.

  34. Rhodes JS, Garland T, Gammie SC (2003) Patterns of brain activity associated with variation in voluntary wheel-running behavior. Behav Neurosci 117:1243–1256.

  35. Robbins TW (2000) Chemical neuromodulation of frontal-executive functions in humans and other animals. Exp Brain Res 133:130–138.

  36. Roelands B, Meeusen R (2010) Alterations in central fatigue by pharmacological manipulations of neurotransmitters in normal and high ambient temperature. Sports Med 40:229–246.

  37. Roelands B, Goekint M, Heyman E et al (2008a) Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature. J Appl Physiol 105:206–212.

  38. Roelands B, Hasegawa H, Watson P et al (2008b) Performance and thermoregulatory effects of chronic bupropion administration in the heat. Eur J Appl Physiol 105:493–498.

  39. Roelands B, Hasegawa H, Watson P et al (2008c) The effects of acute dopamine reuptake inhibition on performance. Med Sci Sports Exerc 40:879–885.

  40. Roelands B, Watson P, Cordery P et al (2012) A dopamine/noradrenaline reuptake inhibitor improves performance in the heat, but only at the maximum therapeutic dose. Scand J Med Sci Sports 22:e93–e98.

  41. Santamaría A, Arias HR (2010) Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats. Behav Brain Res 211:132–139.

  42. Slifstein M, Kolachana B, Simpson EH et al (2008) COMT genotype predicts cortical-limbic D1 receptor availability measured with [11C]NNC112 and PET. Mol Psychiatry 13:821–827.

  43. Spencer TJ, Bonab AA, Dougherty DD et al (2010) A PET study examining pharmacokinetics and dopamine transporter occupancy of two long-acting formulations of methylphenidate in adults. Int J Mol Med 25:261–265.

  44. Stefansky W (2012) Rejecting outliers in factorial designs. Technometrics 14:469–479.

  45. Swart J, Lamberts RP, Lambert MI et al (2009) Exercising with reserve: evidence that the central nervous system regulates prolonged exercise performance. Br J Sports Med 43:782–788.

  46. Treadway MT, Buckholtz JW, Cowan RL et al (2012) Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci 32:6170–6176.

  47. Troiano AR, Schulzer M, la Fuente-Fernandez de R et al (2010) Dopamine transporter PET in normal aging: dopamine transporter decline and its possible role in preservation of motor function. Synapse 64:146–151.

  48. Volkow ND, Fowler JS, Wang G et al (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6(Suppl 1):S31–S43

  49. Volkow ND, Wang G-J, Telang F et al (2008) Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. NeuroImage 42:1537–1543.

  50. Wang GJ, Volkow ND, Logan J et al (2001) Brain dopamine and obesity. Lancet 357:354–357

  51. Warren GL, Park ND, Maresca RD et al (2010) Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis. Med Sci Sports Exerc 42:1375–1387.

  52. Watson P, Hasegawa H, Roelands B et al (2005) Acute dopamine/noradrenaline reuptake inhibition enhances human exercise performance in warm, but not temperate conditions. J Physiol 565:873–883.

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Author information

The roles of the authors were as follows: MK: conception, data acquisition, design, interpretation, and drafting, KVB: data acquisition and drafting, DS: interpretation and drafting, KL: analysis, interpretation, and drafting, and HGLR: interpretation and drafting.

Correspondence to Michael King.

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Novartis did not influence study design, data collection, analysis, interpretation, writing, or decision to submit the article for publication. No authors were paid by Novartis.

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Communicated by Nicolas Place.

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Supplementary Digital Content 1. Custom-built mock-fMRI used during familiarization session (TIF 4585 KB)

Supplementary Digital Content 2. Participants performed 40 grip trials in the power grip position by flexing all digits around a custom-made MRI-compatible isometric handgrip dynamometer. Each grip trial was composed of alternating grip and rest periods, which lasted 12–13 and 5–7 s, respectively. The entire task lasted 13 min and 20 s. A grip trial was defined as failed if a participants’ force dropped below the target force by more than 10 % after having reached the target force (TIF 4525 KB)

Supplementary material 3 (MP4 10970 KB)

Supplementary material 3 (MP4 10970 KB)

Supplementary Digital Content 3. Z score distributions of percent improvement (A), BMI (B), age (C), and min MVPA (D). The outlier value excluded from analyses is indicated in red (PDF 117 KB)

Supplementary material 5 (XLSX 38 KB)

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King, M., Van Breda, K., Stein, D.J. et al. Predicting the ergogenic response to methylphenidate. Eur J Appl Physiol 118, 777–784 (2018).

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  • Ergogenic stimulants
  • Athletic performance
  • Athletic doping
  • Ritalin