Advertisement

Psychopharmacology

, Volume 175, Issue 3, pp 331–341 | Cite as

Impaired executive function in male MDMA (“ecstasy”) users

  • Niels Alting von Geusau
  • Pieter Stalenhoef
  • Mariette Huizinga
  • Jan Snel
  • K. Richard Ridderinkhof
Original Investigation

Abstract

Rationale

Long-term users of ecstasy have shown impaired performance on a multitude of cognitive abilities (most notably memory, attention, executive function). Research into the pattern of MDMA effects on executive functions remains fragmented, however.

Objectives

To determine more systematically what aspects of executive function are affected by a history of MDMA use, by using a model that divides executive functions into cognitive flexibility, information updating and monitoring, and inhibition of pre-potent responses.

Methods

MDMA users and controls who abstained from ecstasy and other substances for at least 2 weeks were tested with a computerized cognitive test battery to assess their abilities on tasks that measure the three submodalities of executive function, and their combined contribution on two more complex executive tasks. Because of sex-differential effects of MDMA reported in the literature, data from males and females were analyzed separately.

Results

Male MDMA users performed significantly worse on the tasks that tap on cognitive flexibility and on the combined executive function tasks; no differences were found on the other cognitive tasks. Female users showed no impairments on any of the tasks.

Conclusions

The present data suggest that a history of MDMA use selectively impairs executive function. In male users, cognitive flexibility was impaired and increased perseverative behavior was observed. The inability to adjust behavior rapidly and flexibly may have repercussions for daily life activities.

Keywords

Ecstasy MDMA Executive function Working memory Flexibility Inhibition Serotonin Dopamine Neurotoxity 

References

  1. Battaglia G, Brooks BP, Kulsakdinun C, De Souza EB (1988) Pharmacological profile of MDMA (3,4-methylenedioxymethylamphetamine) at various brain recognition sites. Eur J Pharmacol 149:159–163PubMedGoogle Scholar
  2. Bolla KI, McCann UD, Ricaurte GA (1998) Memory impairment in abstinent MDMA (“ecstasy”) users. Neurology 5:1532–1537Google Scholar
  3. Botvinick MM, Braver TS, Barch DM, Carter CS, Cohen JD (2001) Conflict monitoring and cognitive control. Psychol Rev 108:624–652CrossRefPubMedGoogle Scholar
  4. Buhot MC (1997) Serotonin receptors in cognitive behaviors. Curr Opin Neurobiol 7:243–254PubMedGoogle Scholar
  5. Commins DL, Vosmer G, Virus RM, Woolverton WL, Schuster CR, Seiden LS (1986) Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther 241:338–345Google Scholar
  6. Crone EA, Ridderinkhof KR, Worms M, Somsen RJM, van der Molen MW (2004) Switching between spatial stimulus-response mappings: a developmental study of cognitive flexibility. Dev Sci (in press)Google Scholar
  7. Derogatis LR (1994) Symptom Check List-90-R: administration, scoring, and procedures manual. National Computer Systems, MinneapolisGoogle Scholar
  8. Dughiero G, Schifano F, Forza G (2001) Personality dimension and psychopathological profiles of ecstasy users. Hum Psychopharmacol 16:635–639CrossRefGoogle Scholar
  9. Epstein CM, Sekino M, Yamaguchi K, Kamiya S, Ueno S (2002) Asymmetries of prefrontal cortex in human episodic memory: effects of transcranial magnetic stimulation on learning abstract patterns. Neurosci Lett 320:5–8CrossRefPubMedGoogle Scholar
  10. Fox HC, Toplis AS, Turner JJD, Parrot AC (2001a) Auditory verbal learning in drug free ecstasy polydrug users. Hum Psychopharmacol 16:613–618Google Scholar
  11. Fox HC, Parrott AC, Turner JJD (2001b) Ecstasy use: cognitive deficits related to dosage rather than self-reported problematic use of the drug. J Psychopharmacol 15:273–281PubMedGoogle Scholar
  12. Fox HC, McLean A, Turner JJD, Parrott AC, Rogers R, Sahakian BJ (2002) Neuropsychological evidence of a relatively selective profile of temporal dysfunction in drug-free MDMA (“ecstasy”) polydrug users. Psychopharmacology 162:203–214CrossRefPubMedGoogle Scholar
  13. Frith CH, Chang LW, Lattin DL, Walls RC, Hamm J, Doblin R (1987) Toxicity of methylenedioxymethylamphetamine (MDMA) in the dog and the rat. Fundam Appl Toxicol 9:110–119PubMedGoogle Scholar
  14. Gerra G, Zaimovic A, Ferri M, Zambelli U, Timpano M, Neri E, Marczocchi GF, Delsignore R, Brambilla F (2000) Long-lasting effects of (±) 3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans. Biol Psychiatry 47:127–136PubMedGoogle Scholar
  15. Gibb JW, Stone DM, Stahl DC, Hanson GR (1987) The effects of amphetamine-like designer drugs on monoaminergic systems in rat brain. NIDA Res Monogr 76:316–321CrossRefPubMedGoogle Scholar
  16. Gouzoulis-Mayfrank E, Dauman J, Tuchtenhagen F, Pelz S, Becker S, Kunert HJ, Fimm B, Sass H (2000) Impaired cognitive performance in drug free users of recreational ecstasy (MDMA). J Neurol Neurosurg Psychiatry 68:719–725PubMedGoogle Scholar
  17. Grant AD, Berg EA (1948) A behavioral analysis of reinforcement and ease of shifting to new responses in a Weigl-type card sorting. J Exp Psychol 38:404–411Google Scholar
  18. Heaton RK, Chelune GJ, Talley JL, Kay GG, Curtiss G (1993) Wisconsin Card Sorting Test Manual: revised and expanded. Psychological assessment Resources, Inc., Odessa, Fla.Google Scholar
  19. Holroyd CB, Coles MGH (2002) The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity. Psychol Rev 109:679–730CrossRefPubMedGoogle Scholar
  20. Hunter AJ (1989) Serotonergic involvement in learning and memory. Biochem Soc Transact 17:79–81PubMedGoogle Scholar
  21. Larson GE, Merritt CR, Williams SE (1998) Information processing and intelligence: some implications of task complexity. Intelligence 12:131–147CrossRefGoogle Scholar
  22. Liechti ME, Gamma A, Vollenweider FX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology 154:161–168PubMedGoogle Scholar
  23. McCann UD, Ridenour A, Shaman Y, Ricaurte GA (1994) Serotonin neurotoxicity after 3,4-nethylenedioxymethylamfetamine (MDMA; “ecstasy”): a controlled study in humans. Neuropsychopharmacology 10:129–138PubMedGoogle Scholar
  24. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA (1998) Positron emission tomography evidence on toxic effects of MDMA (“ecstasy”) on brain serotonin neurons in human beings. Lancet 352:1433–1437PubMedGoogle Scholar
  25. McCann UD, Mertl M, Eligulashvili V, Ricaurte GA (1999) Cognitive performance in 3,4-methylenedioxymethylamfetamine (MDMA, “ecstasy”) users: a controlled study. Psychopharmacology 143:417–425PubMedGoogle Scholar
  26. Milani R, Schifano F (2000) Neuropsychological problems associated with ecstasy use. J Psychopharmacol 14:14Google Scholar
  27. Milner B (1971) Interhemispheric differences in the localization of psychological processes in man. Br Med Bull 27:272–277PubMedGoogle Scholar
  28. Mittenberg W, Motta S (1993) Effects of cocaine abuse on memory and learning. Arch Clin Neuropsychol 8:477–484CrossRefPubMedGoogle Scholar
  29. Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A (2000) The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: a latent variable analysis. Cognit Psychol 41:49–100CrossRefGoogle Scholar
  30. Mokler DJ, Robinson SE, Rosecrans JA (1987) 3,4-Methylenedioxymethylamphetamine (MDMA) produces long-term reductions in brain 5-hydroxytrytamine in rats. Eur J Pharmacol 138:265–268PubMedGoogle Scholar
  31. Morgan MJ (1998) Recreational use of “ecstasy” (MDMA) is associated with elevated impulsivity. Neuropsychopharmacology 19:252–264CrossRefPubMedGoogle Scholar
  32. Morgan MJ (1999) Memory deficits associated with recreational use of “ecstasy” (MDMA). Psychopharmacology 141:30–36CrossRefPubMedGoogle Scholar
  33. Morgan MJ (2000) Ecstasy: a review of its persistent psychological effects. Psychopharmacology 152:230–248PubMedGoogle Scholar
  34. Ornstein TJ, Iddon JL, Baldacchino AM, Sahakian BJ, London M, Everitt BJ, Robbins TW (2000) Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology 23:113–126PubMedGoogle Scholar
  35. O’Shea E, Esteban B, Camarero J, Green AR, Colabo MI (2001) Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA (“ecstasy”) on the 5-HT and dopamine concentrations in mouse brain. Neuropharmacology 40:65–74Google Scholar
  36. Pan HS, Wang RY (1990) The action of MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system. Brain Res 543:56–60CrossRefGoogle Scholar
  37. Parrot AC, Sisk E, Turner JJD (2000) Psychobiological problems in heavy “ecstasy” (MDMA) polydrug users. Drug Alcohol Depend 60:105–110CrossRefGoogle Scholar
  38. Reneman L, Booij J, de Bruin K, Reitsma JB, de Wolff FA, Gunning GB, den Heeten GJ, van den Brink W (2001) Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 385:1864–1869CrossRefGoogle Scholar
  39. Ricaurte GA, McCann UD (1992) Neurotoxic amphetamine analogues: effects in monkeys and implications for humans. Ann N Y Acad Sci 371–382Google Scholar
  40. Ricaurte GA, McCann UD, Szabo Z, Scheffel U (2000) Toxicodynamics and long-term toxicity of the recreational drug, 3,4-methylenedioxymethylamphetamine (MDMA, “ecstasy”). Toxicol Lett 112–113:143–146Google Scholar
  41. Ridderinkhof KR, van der Molen MW (1995) A psychophysiological analysis of developmental differences in the ability to resist interference. Child Dev 66:1040–1056Google Scholar
  42. Ridderinkhof KR, Band GPH, Logan GD (1999) A study of adaptive behavior: effects of age and irrelevant information on the ability to inhibit one’s actions. Acta Psychol 101:315–337CrossRefGoogle Scholar
  43. Ridderinkhof KR, de Vlugt Y, Bramlage A, Spaan M, Elton M, Snel J, Band GPH (2002a) Alcohol consumption impairs the detection of performance errors by mediofrontal cortex. Science 298:2209–2211CrossRefPubMedGoogle Scholar
  44. Ridderinkhof KR, Span MM, van der Molen MW (2002b) Perseverative behavior and adaptive control in older adults: performance monitoring, rule induction, and set shifting. Brain Cognit 49:382–401CrossRefPubMedGoogle Scholar
  45. Rosselli M, Ardila A (1996) Cognitive effects of cocaine and polydrug abuse. J Clin Exp Neuropsychol 18:122–135PubMedGoogle Scholar
  46. Schmidt CJ, Wu L, Lovenberg W (1986) Methylenedioxymethylamphetamine: a potentially neurotoxic amphetamine analogue. Eur J Pharmacol 124:175–178PubMedGoogle Scholar
  47. Schnirman GM, Welsh MC, Retzlaff PD (1998) Development of the Tower of London—revised. Assessment 5:355–360PubMedGoogle Scholar
  48. Schwartz RH, Grueneweld PJ, Klitzner M, Fedio P (1989) Short term memory impairments in cannabis-dependent adolescents. Am J Disord Child 143:1214–1219Google Scholar
  49. Shallice T (1982) Specific impairments in planning. Philos Trans R Soc Lond Series B 298:199–209Google Scholar
  50. Van Boxtel GJM, van der Molen MW, Jennings JR, Brunia CHM (2001) A psychophysiological analysis of inhibitory motor control in the stop-signal paradigm. Biol Psychol 58:229–262CrossRefPubMedGoogle Scholar
  51. Verheyden SL, Hadfield J, Calin T, Curran HV (2002) Sub-acute effects of MDMA (±3,4-methylenedioxymethamphetamine, “ecstasy”) on mood: evidence of gender differences. Psychopharmacology 161:23–31CrossRefPubMedGoogle Scholar
  52. Verkes RJ, Gijsman HJ, Pieters MSM, Schoemaker RC, de Visser S, Kuijpers M, Pennings EJM, de Bruin D, Van de Wijngaart G, Van Gerven JMA, Cohen AF (2001) Cognitive performance and serotonergic function in users of ecstasy. Psychopharmacology 153:196–202PubMedGoogle Scholar
  53. Wareing M, Fisk JE, Murphy PN (2000) Working memory deficits in current and previous users of MDMA (“ecstasy”). Br J Psychol 91:181–188PubMedGoogle Scholar
  54. Zakzanis KK, Young DA (2001a) Memory impairment in abstinent MDMA (“ecstasy”) users: a longitudinal investigation. Neurology 56:966–969PubMedGoogle Scholar
  55. Zakzanis KK, Young DA (2001b) Executive function in abstinent MDMA (“ecstasy”) users. Med Sci Monit 7:1292–1298PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Niels Alting von Geusau
    • 1
  • Pieter Stalenhoef
    • 1
  • Mariette Huizinga
    • 1
  • Jan Snel
    • 1
  • K. Richard Ridderinkhof
    • 1
    • 2
  1. 1.Department of PsychologyUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of PsychologyLeiden UniversityLeidenThe Netherlands

Personalised recommendations