Psychopharmacology

, Volume 167, Issue 1, pp 85–96 | Cite as

Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users

  • R. Thomasius
  • K. Petersen
  • R. Buchert
  • B. Andresen
  • P. Zapletalova
  • L. Wartberg
  • B. Nebeling
  • A. Schmoldt
Original Investigation

Abstract

Rationale

Chronic recreational ecstasy (MDMA) use has often been reported to be associated with psychopathology, memory impairments and serotonergic alterations. However, the findings have not been consistent.

Objectives

To attempt to replicate these findings, to investigate whether such alterations would be reversible and whether they could be predicted by parameters of previous drug use.

Methods

In a cross-sectional design, 30 current and 31 ex-ecstasy users with ecstasy abstinence of at least 5 months, and 29 polydrug and 30 drug-naive controls were compared on measures of psychopathology, cognitive performance and serotonin transporter availability.

Results

The groups did not differ significantly in age, gender distribution, education level and premorbid intelligence. The ecstasy groups did not differ significantly from polydrug controls on most of the relevant parameters of concomitant illegal drug use. Reported drug use was confirmed by hair and urine analyses. All three groups of drug users exhibited significantly elevated psychopathology compared with drug-naive controls. Only ex-ecstasy users were significantly impaired on verbal recall. Current ecstasy users showed significantly reduced distribution volume ratios of serotonin transporter availability in the mesencephalon and caudate nucleus. Regression analyses indicated that psychopathology and serotonergic alterations were best predicted by the number of ecstasy tablets taken on a typical event.

Conclusion

The results indicate that verbal memory impairments were possibly aggravated after prolonged ecstasy abstinence while there was tentative evidence of serotonergic recovery. On the other hand, self-reported elevated psychopathology appeared to be associated with polydrug use in general and not specifically with ecstasy use.

Keywords

3-4-Methylenedioxymethamphetamine MDMA Ecstasy Psychopathology Cognitive performance Neuroimaging 

Notes

Acknowledgements

The study was supported by a grant (No. Z12.01-68503-206) from the BfArM (Federal Institute for Drugs and Medical Devices). Thanks to D. Abed, C. Berndt, C. Carballo-Wandel, I. Christensen, A. Goerling, F. Goetz, J. Hinrichsen, A. Iida, K. Marquardt, M. Neukamp, S. Rippe, B. Schmidt, P. Schmitter, N. Schnakenberg, U. Strassburger, J. Tammen, B. Treder and M. Wenzel for their contributions to the recruitment and assessment of participants.

References

  1. Acton PD, Friston KJ (1998) Statistical parametric mapping in functional neuroimaging: beyond PET and fMRI activation studies. Eur J Nucl Med 25:663–667PubMedGoogle Scholar
  2. Bäumler G (1974) Lern- und Gedächtnistest LGT-3. Hogrefe, GöttingenGoogle Scholar
  3. Bhattachary S, Powell JH (2001) Recreational use of 3,4-methylenedioxymethamphetamine (MDMA) or "ecstasy": evidence for cognitive impairment. Psychol Med 31:647–658CrossRefPubMedGoogle Scholar
  4. Bolla KI, McCann UD, Ricaurte GA (1998) Memory impairment in abstinent MDMA ("Ecstasy") users. Neurology 51:1532–1537PubMedGoogle Scholar
  5. Buchert R, Obrocki J, Thomasius R, Väterlein O, Petersen K, Jenicke L, Bohuslavizki, Clausen M (2001) Long term effects of "ecstasy"-abuse on the human brain studied by FDG PET. Nucl Med Commun 22:889–897CrossRefPubMedGoogle Scholar
  6. Buck A, Gucker PM, Schonbachler RD, Arigoni M, Kneifel S, Vollenweider FX, Ametamey SM, Burger C (2000) Evaluation of serotonergic transporters using PET and [11C](+)McN-5652: assessment of methods. J Cereb Blood Flow Metab 20: 253–262Google Scholar
  7. Cole J, Sumnall H, Grob C (2002) Sorted: ecstasy, facts and fiction. Psychologist 15:464–467Google Scholar
  8. Croft RJ, Mackay AJ, Mills AT, Gruzelier JG (2001) The relative contributions of ecstasy and cannabis to cognitive impairment. Psychopharmacology: 153:373–379Google Scholar
  9. Derogatis LR (1994) The SCL-90-R scoring manual. Distributed by National computer Systems, MinneapolisGoogle Scholar
  10. Deykin EY, Levy JC, Wells V (1986) Adolescent depression, alcohol and drug abuse. Am J Public Health 76:178–182PubMedGoogle Scholar
  11. EMCDDA (European Monitoring Centre for Drugs and Drug Addiction) (2002) Annual report on the state of the drugs problem in the European Union. Office for Official Publications of the European Communities, LuxembourgGoogle Scholar
  12. Fox HC, Toplis AS, Turner JJD, Parrott AC (2001) Auditory verbal learning in drug-free ecstasy polydrug users. Hum Psychopharmacol Clin Exp 16:613–618Google Scholar
  13. Franke G (1995) Die Symptom-Checkliste von Derogatis (SCL-90-R). Beltz, GöttingenGoogle Scholar
  14. Gamma A, Frei E, Lehmann D, Pascual RD, Hell D, Vollenweider FX (2000) Mood state and brain electric activity in ecstasy users. Neuroreport 11:157–162PubMedGoogle Scholar
  15. Gamma A, Frei E, Lehmann D, Pascual RD, Hell D, Vollenweider FX (2001) Mood state and brain electric activity in ecstasy users. Neuroreport 11:157–162Google Scholar
  16. Gerra G, Zaimovic A, Giucastro G, Maestri D, Monica C, Sartori R et al. (1998) Serotonergic function after 3,4-methylenedioxymethamphetamine ("ecstasy") in humans. Int Clin Psychopharmacol 13:1–9PubMedGoogle Scholar
  17. Gerra G, Zaimovic A, Ferri M, Zambelli U, Timpano M et al. (2000) Long-lasting effects of 3,4-methylenedioxymethamphetamine (ecstasy) on serotonin system function in humans. Biol Psychiatry 47:127–136PubMedGoogle Scholar
  18. Gouzoulis-Mayfrank E, Daumann J, Tuchtenhagen F, Pelz S, Becker S, Kunert H-K, Fimm B, Sass H (2000) Impaired cognitive performance in drug free users of recreational ecstasy (MDMA). J Neurol Neurosurg Psychiatry 68:719–725PubMedGoogle Scholar
  19. Gsellhofer B, Fahrner EM, Platt J (1994) European Addiction Severity Index (EuropASI). Institute for Therapy Research (IFT), Munich, GermanyGoogle Scholar
  20. Hatzidimitriou G, McCann UD, Ricaurte GA (1999) Altered serotonin innervation patterns in the forebrain of monkeys treated with (±) 3,4-methylenedioxymethamphetamine seven years previously: factors influencing abnormal recovery. J Neurosci 19:5096–5107PubMedGoogle Scholar
  21. Heaton RK, Cheleene GJ, Talley JL, Kay GG, Curtiss G (1993) The Wisconsin Card Sorting Test (WCST) Manual—revised and expanded. Psychological Assessment Resources, Odessa, Fla.Google Scholar
  22. Ichise M, Ballinger JR, Golan H, Vines D, Luong A, Tsai S, Kung HF (1996) Noninvasive quantification of dopamine D2 receptors with iodine-123-IBF SPECT. J Nucl Med 37:513–520PubMedGoogle Scholar
  23. Ichise M, Meyer JH, Yonekura Y (2001) An introduction to PET and SPECT neuroreceptor quantification models. J Nucl Med 42:755–763PubMedGoogle Scholar
  24. Jäger AO, Althoff K (1994) Der Wilde-Intelligenz-Test (WIT)—ein Strukturdiagnostikum. Hogrefe, GöttingenGoogle Scholar
  25. Khantzian EJ (1997) The self-medication hypothesis of substance abuse disorders: a reconsideration and recent applications. Harv Rev Psychiatry 4:231–244PubMedGoogle Scholar
  26. Kish SJ (2002) How strong is the evidence that brain serotonin neurons are damaged in human users of ecstasy? Pharmacol Biochem Behav 71:845–855CrossRefPubMedGoogle Scholar
  27. Kish SJ, Furukawa Y, Ang L, Vorce SP, Kalasinsky KS (2000) Striatal serotonin is depleted in brain of a human MDMA (ecstasy) user. Neurology 55:294–296PubMedGoogle Scholar
  28. Klugman A, Hardy S, Baldeweg T, Gruzelier J (1999) Toxic effect of MDMA on brain serotonin neurons. Lancet 353:1269–1271Google Scholar
  29. Laruelle M, Vanisberg MA, Maloteaux JM (1988) Regional and subcellular localization in human brain of [3H]paroxetine binding, a marker of serotonin uptake sites. Biol Psychiatry 24:299–309Google Scholar
  30. Lehrl S (1995) Mehrfach-Wortschatz-Intelligenztest (MWT-B), 3. überarb. Aufl. Med. Verlagsgesellschaft, BalingenGoogle Scholar
  31. Lezak MD (1983) Neuropsychological assessment, 2nd edn. Oxford University Press, New YorkGoogle Scholar
  32. McCann UD, Ridenour A, Shaham Y, Ricaurte GA (1994) Serotonin neurotoxicity after (±) 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") users: a controlled study in humans. Neuropsychopharmacology 10:129–138PubMedGoogle Scholar
  33. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA (1998) Positron emission tomographic evidence of toxic effect of MDMA ("ecstasy") on brain serotonin neurons in human beings. Lancet 352:1433–1437PubMedGoogle Scholar
  34. McCann UD, Mertl M, Eligulashvili V, Ricaurte GA (1999) Cognitive performance in (±) 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") users: a controlled study. Psychopharmacology 143:417–425PubMedGoogle Scholar
  35. McGuire PK, Cope H, Fahy TA et al. (1994) Diversity of psychopathology associated with use of 3,4-methylenedioxymethamphetamine ("ecstasy"). Br J Psychiatry 165:391–395PubMedGoogle Scholar
  36. McLellan AT, Kushner H, Metzger D, Peters R, Smith I, Grissom G, Pettinati H, Argeriou M (1992) The fifth edition of the Addiction Severity Index. J Subst Abuse Treat 9:199–213CrossRefPubMedGoogle Scholar
  37. Morgan MJ (1999) Memory deficits associated with recreational use of "ecstasy" (MDMA). Psychopharmacology 141:30–36CrossRefPubMedGoogle Scholar
  38. Morgan MJ (2002) Throwing the baby out with the bath water? Psychologist 15:468–469Google Scholar
  39. Morgan MJ, McFie L, Fleetwood LH, Robinson JA (2002) Ecstasy (MDMA): are the psychological problems associated with its use reversed by prolonged abstinence? Psychopharmacology 159:294–303PubMedGoogle Scholar
  40. Obrocki J, Buchert R, Väterlein O, Thomasius R, Beyer W, Schiemann T (1999) Ecstasy—long term effects on the human central nervous system revealed by positron emission tomography. Br J Psychiatry 175:186–188PubMedGoogle Scholar
  41. Parrott AC (2001)Human psychopharmacology of ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol Clin Exp 16:557–577Google Scholar
  42. Parrott AC (2002) Very real, very damaging. Psychologist 15:472–473Google Scholar
  43. Parrott AC, Lees A, Garnham NJ, Jones M, Wesnes K (1998) Cognitive performance in recreational users of MDMA or "ecstasy": evidence for memory deficits. J Psychopharmacol 12:79–83PubMedGoogle Scholar
  44. Parrott AC, Sisk E, Turner JJD (2000) Psychobiological problems in heavy "ecstasy" (MDMA) polydrug users. Drug Alcohol Depend 60:105–110PubMedGoogle Scholar
  45. Parrott AC, Milani RM, Parmar R, Turner JD (2001) Recreational ecstasy/MDMA and other drug users from the UK and Italy: psychiatric symptoms and psychobiological problems. Psychopharmacology 159:77–82PubMedGoogle Scholar
  46. Parsey RV, Kegeles LS, Hwang DR, Simpson N, Abi-Dargham A, Mawlawi O, Slifstein M, Van Heertum RL, Mann JJ, Laruelle M (2000) In vivo quantification of brain serotonin transporters in humans using [11C]McN5652. J Nucl Med 41:1465–1477PubMedGoogle Scholar
  47. Reitan RM (1992) Trail Making Test—manual for administration and scoring. Reitan Neuropsychology Laboratory, Tucson, ArizonaGoogle Scholar
  48. Reneman L, Booij J, Schmand B, Brink W, Gunning B (2000) Memory disturbances in "ecstasy" users are correlated with an altered serotonin neurotransmission. Psychopharmacology 148:322–324PubMedGoogle Scholar
  49. Reneman L, Lavalaye J, Schmand B, De Wolff FA, van den Brink W, den Heeten GJ, Booij J (2001a) Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Arch Gen Psychiatry 58:901–906PubMedGoogle Scholar
  50. Reneman L, Booij J, de Bruin K, Reitsma JB, de Wolff FA, Gunning WB, den Heeten GI, van den Brink W (2001b) Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 358:1864–1869PubMedGoogle Scholar
  51. Reneman L, Majoie CBLM, Schmand B, van den Brink W, den Heeten GJ (2001c) Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) ecstasy users: preliminary report. Biol Psychiatry 50:550–554CrossRefPubMedGoogle Scholar
  52. Reneman L, Majoie CBLM, Flick H, den Heeten GJ (2002) Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (ecstasy) users: preliminary results. Am J Neuroradiol 23:231–237PubMedGoogle Scholar
  53. Ricaurte GA, Finnegan KT, Irwin I, Langston JW (1990) Aminergic metabolites in cerebrospinal fluid of humans previously exposed to MDMA: preliminary observations. Ann NY Acad Sci 600:699–710PubMedGoogle Scholar
  54. Ricaurte GA, Yuan J, McCann UD (2000) (±) 3,4-Methylenedioxymethamphetamine ("ecstasy")-induced serotonin neurotoxicity: studies in animals. Neuropsychobiology 42:5-10PubMedGoogle Scholar
  55. Rodgers J (2000) Cognitive performance amongst recreational users of "ecstasy". Psychopharmacology 151:19–24PubMedGoogle Scholar
  56. Scheffel U, Szabo Z, Mathews WB, Finley PA, Dannals RF, Ravert HT, Szabo K, Yuan J, Ricaurte GA (1998) In vivo detection of short- and long-term MDMA neurotoxicity—a positron emission tomography study in the living baboon brain. Synapse 29:183–192CrossRefPubMedGoogle Scholar
  57. Schuster P, Lieb R, Lamertz C, Wittchen HU (1998) Is the use of ecstasy and hallucinogens increasing? Eur Addict Res 4:75–82PubMedGoogle Scholar
  58. Semple DM, Ebmeier KP, Glabus MF, O'Carroll RE, Johnstone EC (1999) Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ("ecstasy") users. Br J Psychiatry 175:63–69PubMedGoogle Scholar
  59. Simon et al. (2001)Google Scholar
  60. Strote J, Lee JE, Wechsler H (2002) Increasing MDMA use among college students: result of a national survey. J Adolesc Health 72:64–72CrossRefGoogle Scholar
  61. Suehiro M, Ravert HT, Dannals RF, Scheffel U, Wagner HN (1992) Synthesis of a radiotracer for studying serotonin uptake sites with positron emission tomography: [11C]McN-5652-Z. J Label Comp Radiopharm 31:841–848Google Scholar
  62. Suehiro M, Scheffel U, Ravert HT, Dannals RF, Wagner HN (1993) [11C](+)McN5652 as a radiotracer for imaging serotonin uptake sites with PET. Life Sci 53:883–892PubMedGoogle Scholar
  63. Szabo Z, Kao PF, Scheffel U (1995) Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652. Synapse 20:37–43Google Scholar
  64. Szabo Z, Kao PF, Mathews WB, Ravert HT, Musachio JL, Scheffel U, Dannals RF (1996) Positron emission tomography of 5-HT reuptake sites in the human brain with C-11 McN5652 extraction of characteristic images by artificial neural network analysis. Behav Brain Res 73:221–222PubMedGoogle Scholar
  65. Szabo Z, McCann UD, Wilson AA, Scheffel U, Owonikoko T, Mathews WB, Ravert HT, Hilton J, Dannals RF, Ricaurte (2002) Comparison of (+)-11 C-McN5652 and C11-DASB as serotonin transporter radioligands under various experimental conditions. J Nucl Med 43:678–692PubMedGoogle Scholar
  66. Tewes U (1994) HAWIE-R: Hamburg Wechsler Intelligenztest für Erwachsene, Revision 1991. Huber, BernGoogle Scholar
  67. Thomasius R (ed) (2000) Ecstasy. Eine Studie zu gesundheitlichen und psychosozialen Folgen des Missbrauchs. Wissenschaftliche Verlagsgesellschaft, StuttgartGoogle Scholar
  68. Tossmann P, Boldt S, Tensil MD (2001) The use of drugs within the Techno Party Scene in European Metropolitan Cities. Eur Addict Res 7:2–23CrossRefPubMedGoogle Scholar
  69. Tuchtenhagen F, Daumann J, Norra C, Gobbele R, Becker S, Pelz S, Sass H, Buchner H, Gouzoulis-Mayfrank E (2000) High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users. Neuropsychopharmacology 22:608–617Google Scholar
  70. Verkes RJ, Gijsman HJ, Pieters MS, Schoemaker RC, de Visser S, Kuijpers M, Pennings EJ, de Bruin D, Van de Wijngaart G, Van Gerven JM, Cohen AF (2001) Cognitive performance and serotonergic function in users of ecstasy. Psychopharmacology 153:196–202PubMedGoogle Scholar
  71. 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
  72. Weeks RA, Cunningham VJ, Piccini P, Waters S, Harding AE, Brooks DJ (1997) 11C-Diprenorphine binding in Huntington's disease: a comparison of region of interest analysis with statistical parametric mapping. J Cereb Blood Flow Metab 17:943–949PubMedGoogle Scholar
  73. Wienhard K, Eriksson L, Grootoonk S, Casey M (1992) Performance evaluation of the positron scanner ECAT EXACT. J Comput Assist Tomogr 16:804–813Google Scholar
  74. Wilson B, Cockburn J, Baddeley A (1985) The Rivermead Behavioural Memory Test. Thames Valley Text, ReadingGoogle Scholar
  75. Wittchen HU, Zaudig M, Fytrich T (1997) Strukturiertes klinisches Interview für DSM-IV (SKID I and II, Structured clinical interview for the DSM-IV). Hogrefe, GöttingenGoogle Scholar
  76. Zakzanis KK, Young DA (2001) Executive function in abstinent MDMA ("ecstasy") users. Med Sci Monit 7:1292–1298PubMedGoogle Scholar
  77. Zimmermann P, Flimm B (1993) Testbatterie zur Aufmerksamkeitsprüfung (TAP) Version 1.02. Vera Fimm/Psychologische Testsysteme, WuerselenGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • R. Thomasius
    • 1
  • K. Petersen
    • 1
  • R. Buchert
    • 2
  • B. Andresen
    • 1
  • P. Zapletalova
    • 1
  • L. Wartberg
    • 1
  • B. Nebeling
    • 2
  • A. Schmoldt
    • 3
  1. 1.Department of Psychiatry and PsychotherapyUniversity Hospital Hamburg-EppendorfHamburgGermany
  2. 2.Department of Nuclear MedicineUniversity Hospital Hamburg-EppendorfHamburgGermany
  3. 3.Institute of Forensic MedicineUniversity Hospital Hamburg-EppendorfHamburgGermany

Personalised recommendations