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Designer drugs: how dangerous are they?

  • L. Reneman
Conference paper

Summary

Of the designer drugs, the amphetamine analogues are the most popular and extensively studied, ecstasy (3,4-methylenedioxymetham-phetamine; MDMA) in particular. They are used recreationally with increasing popularity despite animal studies showing neurotoxic effects to serotonin (5-HT) and/or dopamine (DA) neurones. However, few detailed assessments of risks of these drugs exist in humans. Previously, there were no methods available for directly evaluating the neurotoxic effects of amphetamine analogues in the living human brain. However, development of in vivo neuroimaging tools have begun to provide insights into the effects of MDMA in human brain. In this review, contributions of brain imaging studies on the potential 5-HT and/or DA neurotoxic effects of amphetamine analogues will be highlighted in order to delineate the risks these drugs engender in humans, focusing on MDMA. An overview will be given of PET, SPECT and MR Spectroscopy studies employed in human users of these drugs. Most of these studies provide suggestive evidence that MDMA is neurotoxic to 5-HT neurones, and (meth)amphetamine to DA neurones in humans. These effects seem to be dose-related, leading to functional impairments such as memory loss, and are reversible in several brain regions. However most studies have had a retrospective design, in which evidence is indirect and differs in the degree to which any causative links can be implied between drug use and neurotoxicity. Therefore, at this moment, it cannot be ascertained that humans are susceptible to MDMA-induced 5-HT injury or (meth)amphetamine-induced DA injury. Finally, although little is known about other amphetamine analogues there are important questions as to the safety of these designer drugs as well, in view of the fact that they are chemically closely related to MDMA and some have been shown to be 5-HT neurotoxins in animals.

Keywords

Neurotoxic Effect Ecstasy User Mdma User Methamphetamine User Living Human Brain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ahmad K (2002) Increased use of amphetamine-type stimulants threatens east Asian countries. Lancet 359: 1927PubMedCrossRefGoogle Scholar
  2. Backstrom I, Bergstrom M, Marcusson J (1989) High affinity [3H]paroxetine binding to serotonin uptake sites in human brain tissue. Brain Res 486: 261–268PubMedCrossRefGoogle Scholar
  3. Bakhit C, Morgan ME, Peat MA, Gibb JW (1981) Long-term effects of methamphet-amine on the synthesis and metabolism of 5-hydroxytryptamine in various regions of the rat brain. Neuropharmacology 20: 1135–1140PubMedCrossRefGoogle Scholar
  4. Battaglia G, Yeh SY, O’Hearn E, Molliver ME, Kuhar MJ, De Souza EB (1987) 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. J Pharmacol Exp Ther 242: 911–916PubMedGoogle Scholar
  5. Battaglia G, Yeh SY, De Souza EB (1988) MDMA-induced neurotoxicity: parameters of degeneration and recovery of brain serotonin neurons. Pharmacol Biochem Behav 29: 269–274PubMedCrossRefGoogle Scholar
  6. Boja JW, Patel A, Carroll FI, Rahman MA, Philip A, Lewin AH, Kopajtic TA, Kuhar MJ (1991) [125I]RTI-55: a potent ligand for dopamine transporters. Eur J Pharmacol 194: 133–134PubMedCrossRefGoogle Scholar
  7. Boja JW, McNeill RM, Lewin AH, Abraham P, Carroll FI, Kuhar MJ (1992) Selective dopamine transporter inhibition by cocaine analogs. Neuroreport 3: 984–986PubMedCrossRefGoogle Scholar
  8. Cass WA, Manning MW (1999) Recovery of presynaptic dopaminergic functioning in rats treated with neurotoxic doses of methamphetamine. J Neurosci 19: 7653–7660PubMedGoogle Scholar
  9. Chang L, Ernst T, Grob CS, Poland RE (1999) Cerebral 1H MRS alterations in recreational 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) users. J Magn Reson Imaging 10: 521–526PubMedCrossRefGoogle Scholar
  10. Commins DL, Seiden LS (1986) alpha-Methyltyrosine blocks methylamphetamine-induced degeneration in the rat somatosensory cortex. Brain Res 365: 15–20PubMedCrossRefGoogle Scholar
  11. Commins DL, Vosmer G, Virus RM, Woolverton WL, Schuster CR, Seiden, LS (1987) Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. J Pharmacol Exp Ther 241: 338–345PubMedGoogle Scholar
  12. Curran HV (2000) Is MDMA (‘Ecstasy’) neurotoxic in humans? An overview of evdience and of methodological problems in research. Neuropsychobiology 42: 34–41PubMedCrossRefGoogle Scholar
  13. EMCDDA (2001) Annual report on the state of the drugs problem in the European Union. http://annualreport.emcdda.org/multimedia/Annual_Report_2001/ar01_en.pdf
  14. Ernst T, Chang L, Leonido-Yee M, Speck O (2000) Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study. Neurology 54:1344–1349PubMedCrossRefGoogle Scholar
  15. Farde L, Halldin C, Muller L, Suhara T, Karlsson P, Hall H (1994) PET study of [11C]β-CIT binding to monoamine transporters in the monkey and human brain. Synapse 16: 93–103PubMedCrossRefGoogle Scholar
  16. Friedman SD, Castaneda E, Hodge GK (1998) Long-term monoamine depletion, differential recovery, and subtle behavioral impairment following methamphetamine-in-duced neurotoxicity. Pharmacol Biochem Behav 61: 35–44PubMedCrossRefGoogle Scholar
  17. Frost JJ, Rosier AJ, Reich SG, Smith JS, Ehlers MD, Snyder SH, Ravert HT, Dannais RF (1993) Positron emission tomographic imaging of the dopamine transporter with 11C-WIN 35,428 reveals marked declines in mild Parkinson’s disease. Ann Neurol 34: 423–431PubMedCrossRefGoogle Scholar
  18. 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: 316–321PubMedGoogle Scholar
  19. Gijsman HJ, Verkes RJ, van Gerven JMA, Cohen AF (1999) MDMA study. Neuropsychopharmacology 21: 597PubMedCrossRefGoogle Scholar
  20. Gurevich EV, Joyce JN (1996) Comparison of [3H]paroxetine and [3H]cyanoimipramine for quantitative measurement of serotonin transporter sites in human brain. Neuropsychopharmacology 14:309–323PubMedCrossRefGoogle Scholar
  21. Harvey DC, Lacan G, Tanious SP, Melega WP (2000) Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss. Brain Res 871: 259–270PubMedCrossRefGoogle Scholar
  22. Hatzidimitriou G, McCann UD, Ricaurte GA (1999) Altered serotonin innervation patterns in the forebrain of monkeys treated with (+/-)3,4-methylenedioxy-methamphetamine seven years previously: factors influencing abnormal recovery. J Neurosci 19: 5096–5107PubMedGoogle Scholar
  23. Hegadoren KM, Baker GB, Bourin M (1999) 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans. Neurosci Biobehav Rev 23: 539–553PubMedCrossRefGoogle Scholar
  24. Higuchi T, Graham SH, Fernandez EJ, Rooney WD, Gaspary HL, Weiner MW, Maudsley AA (1997) Effects of severe global ischemia on N-acetylaspartate and other metabolites in the rat brain. Magn Reson Med 37: 851–857PubMedCrossRefGoogle Scholar
  25. Howe FA, Maxwell RJ, Saunders DE, Brown MM, Griffiths JR (1993) Proton spectroscopy in vivo. Magn Reson Q 9: 31–59Google Scholar
  26. Huang X, Marona-Lewicka D, Nichols DE (1992) p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. Eur J Pharmacol 229: 31–38PubMedCrossRefGoogle Scholar
  27. Johnson MP, Hoffman AJ, Nichols DE (1986) Effects of the enantiomers of MDA, MDMA and related analogues on [3H] serotonin and [3H] dopamine release from superfused rat brain slices. Eur J Pharmacol 132: 269–276PubMedCrossRefGoogle Scholar
  28. Johnston LD, O’Malley PM, Bachman JG (2002) Monitoring the future national results on adolescent drug use: overview of key findings, 2001. National Institute of Drug Abuse, Bethesda, MD (NIH Pub. No. 02-5105)Google Scholar
  29. Kamien JB, Johanson CE, Schuster CR, Woolverton WL (1986) The effects of (+/-)-methylenedioxymethamphetamine and (+/-)-methylenedioxyamphetamine in monkeys trained to discriminate (+)-amphetamine from saline. Drug Alcohol Depend 18: 139–147PubMedCrossRefGoogle Scholar
  30. Kieven MS, Seiden LS (1992) Methamphetamine-induced neurotoxicity: structure activity relationships. Ann NY Acad Sci 654: 292–301CrossRefGoogle Scholar
  31. Kish SJ (2002) How strong is the evidence that brain serotonin neurons are damaged in human users of ecstasy? Pharmacol Biochem Behav 71: 845–855PubMedCrossRefGoogle Scholar
  32. Koda LY, Gibb JW (1973) Adrenal and striatal tyrosine hydroxylase activity after methamphetamine. J Pharmacol Exp Ther 185: 42–48PubMedGoogle Scholar
  33. Kuikka JT, Tiihonen J, Bergstrom KA, Karhu J, Hartikainen P, Viinamaki H, Lansimies E, Lehtonen J, Hakola P (1995) Imaging of serotonin and dopamine transporters in the living human brain. Eur J Nucl Med 22: 346–350PubMedCrossRefGoogle Scholar
  34. Laruelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, al-Tikriti MS, Sybirska EH, Zimmermann RC, Wisniewski G, Neumeyer JL (1993) SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 13: 295–309PubMedCrossRefGoogle Scholar
  35. Lew R, Sabol KE, Chou C, Vosmer GL, Richards J, Seiden LS (1996) Methylenedioxymethamphetamine-induced serotonin deficits are followed by partial recovery over a 52-week period, part II. Radioligand binding and autoradiography studies. J Pharmacol Exp Ther 276: 855–865PubMedGoogle Scholar
  36. Melega WP, Quintana J, Raleigh MJ, Stout DB, Yu DC, Lin KP, Huang SC, Phelps ME (1996) 6-[18F]fluoro-L-DOPA-PET studies show partial reversibility of long-term effects of chronic amphetamine in monkeys. Synapse 22: 63–69PubMedCrossRefGoogle Scholar
  37. Melega WP, Raleigh MJ, Stout DB, Lacan G, Huang SC, Phelps ME (1997) Recovery of striatal dopamine function after acute amphetamine— and methamphetamine-induced neurotoxicity in the vervet monkey. Brain Res 766: 113–120PubMedCrossRefGoogle Scholar
  38. McCann UD, Ricaurte GA (2001) Caveat emptor: editors beware. Neuropsycho-pharmacology 24: 333–334CrossRefGoogle Scholar
  39. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA (1998a) Positron emission tomographic evidence of toxic effect of MDMA (“Ecstasy”) on brain serotonin neurones in human beings. Lancet 352: 1433–1437PubMedCrossRefGoogle Scholar
  40. McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA (1998b) Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with [11C]WIN-35,428. J Neurosci 18: 8417–8422PubMedGoogle Scholar
  41. McKenna DJ, Guan XM, Shulgin AT (1991) 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine. Pharmacol Biochem Behav 38: 505–512PubMedCrossRefGoogle Scholar
  42. Molliver ME, Berger UV, Mamounas LA, Molliver DC, O’Hearn E, Wilson, MA (1990) Neurotoxicity of MDMA and related compounds: anatomic studies. Ann NY Acad Sci 600: 649–661PubMedCrossRefGoogle Scholar
  43. Mordenti J, Chappell (1989) The use of interspecies scaling in toxicokinetics. In: Yacobi A, Kelly J, Batra V (eds) Toxicokinetics and new drug development. Pergamon Press, New York, pp 42–96Google Scholar
  44. Obergriesser T, Ende G, Braus DF, Henn FA (2001) Hippocampal 1H-MRSI in ecstasy users. Eur Arch Psychiatry Clin Neurosci 251: 114–116PubMedCrossRefGoogle Scholar
  45. O’Hearn E, Battaglia G, De Souza EB, Kuhar MJ, Molliver ME (1988) Methylenedioxy-amphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity. J Neurosci 8: 2788–2803PubMedGoogle Scholar
  46. Parrott AC (2000) Human research on MDMA (3,4-methylenedioxymethamphetamine) neurotoxicity: cognitive and behavioural indices of change. Neuropsychobiology 42: 17–24PubMedCrossRefGoogle Scholar
  47. Parsey RV, Kegeies 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]McN 5652. J Nucl Med 41: 1465–1477PubMedGoogle Scholar
  48. Pirker W, Asenbaum S, Hauk M, Kandlhofer S, Tauascher J, Willeit M, Neurmeister A, Praschak-Rieder N, Angelberger P, Brücke T (2000) Imaging serotonin and dopamine transporters with 123I-β-CIT SPECT: binding kinetics and effects of normal aging. J Nucl Med 41: 36–44PubMedGoogle Scholar
  49. Pope HG Jr, Ionescu-Pioggia M, Pope KW (2001) Drug use and life style among college undergraduates: a 30-year longitudinal study. Am J Psychiatry 158: 1519–1521PubMedCrossRefGoogle Scholar
  50. Reneman L, Booij J, Schmand B, van den Brink W, Gunning B (2000a) Memory disturbances in “Ecstasy” users are correlated with an altered brain serotonin neurotransmission. Psychopharmacology 148: 322–324PubMedCrossRefGoogle Scholar
  51. Reneman L, Booij J, de Bruin K, de Wolff FA, Gunning WB, den Heeten GJ, vd Brink W (2001a) Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 358: 1864–1869PubMedCrossRefGoogle Scholar
  52. Reneman L, Lavalaye J, Booij J, Schmand B, de Wolff FA, vd Brink W, den Heeten GJ, Booij J (2001b) Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethaphetamine (MDMA or “Ecstasy”) — preliminary findings. Arch Gen Psychiatry 58: 901–906PubMedCrossRefGoogle Scholar
  53. Reneman L, Majoie CBLM, Schmand B, vd Brink W, den Heeten GJ (2001c) Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) Ecstasy users: preliminary report. Biol Psychiatry 50: 550–554PubMedCrossRefGoogle Scholar
  54. Reneman L, Majoie CBLM, Habraken JBA, den Heeten GJ (2001d) Diffusion and the effects of Ecstasy (MDMA) on the brain in abstinent users: initial observations with diffusion and perfusion MR imaging. Radiology 220: 611–617PubMedCrossRefGoogle Scholar
  55. Reneman L, Booij J, Habraken JBA, de Bruin K, Hatzidimitriou G, den Heeten GJ, Ricaurte GA (2002a) Validity of [123I]β-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity. Synapse 46: 199–205PubMedCrossRefGoogle Scholar
  56. Reneman L, Majoie CBLM, Flick H, den Heeten GJ (2002b) Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethaphetamine (“Ecstasy”) users — preliminary results. AJNR Am J Neuroradiol 23: 231–237PubMedGoogle Scholar
  57. Reneman L, Booij J, Lavalaye J, de Bruin K, Reitsma JB, Gunning WB, den Heeten GJ, van den Brink W (2002c) Use of amphetamine by recreational users of ecstasy is associated with reduced striatal dopamine transporter densities: a [123I]β-CIT SPECT study. Psychopharmacology 159: 335–340PubMedCrossRefGoogle Scholar
  58. Ricaurte GA, McCann UD (1992b) Neurotoxic amphetamine analogues: effects in monkeys and implications for humans. Ann NY Acad Sci 648: 371–382PubMedCrossRefGoogle Scholar
  59. Ricaurte GA, Schuster CR, Seiden LS (1980) Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional study. Brain Res 193: 153–163PubMedCrossRefGoogle Scholar
  60. Ricaurte G, Bryan G, Strauss L, Seiden L, Schuster C (1985) Hallucinogenic amphetamine selectively destroys brain serotonin nerve terminals. Science 229: 986–988PubMedCrossRefGoogle Scholar
  61. Ricaurte GA, DeLanney LE, Irwin I, Langsten JW (1988) Toxic effects of MDMA on central serotonergic neurones in the primate: importance of route and frequency of drug administration. Brain Res 446: 165–168PubMedCrossRefGoogle Scholar
  62. Ricaurte GA, Martello AL, Katz JL, Martello MB (1992a) Lasting effects of (+/-)-3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in non-human primates: neurochemical observations. J Pharmacol Exp Ther 261: 616–622PubMedGoogle Scholar
  63. Ricaurte GA, Yuan J, McCann UD (2000) (+/-)3,4-Methylenedioxymethamphetamine (“Ecstasy”)-induced serotonin neurotoxicity: studies in animals. Neuropsychobiology 42: 5–10PubMedCrossRefGoogle Scholar
  64. Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD (2002) Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA (“ecstasy”). Science 297: 2260–2263PubMedCrossRefGoogle Scholar
  65. Ridley RM, Baker HF, Owen F, Cross AJ, Crow TJ (1982) Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey. Psychopharmacology 78: 245–251PubMedCrossRefGoogle Scholar
  66. Ryan LJ, Linder JC, Martone ME, Groves PM (1990) Histological and ultrastructural evidence that D-amphetamine causes degeneration in neostriatum and frontal cortex of rats. Brain Res 518: 67–77PubMedCrossRefGoogle Scholar
  67. Scanzello CR, Hatzidimitriou G, Martello AL, Katz JL, Ricaurte GA (1993) Serotonergic recovery after (+/-)3,4-(methylenedioxy) methamphetamine injury: observations in rats. J Pharmacol Exp Ther 264: 1484–1491PubMedGoogle Scholar
  68. Scheffel U, Ricaurte GA (1990) Paroxetine as an in vivo indicator of 3,4-methylenedioxymethamphetamine neurotoxicity: a presynaptic serotonergic positron emission tomograpy ligand? Brain Res 527: 89–95PubMedCrossRefGoogle Scholar
  69. Scheffel U, Dannals RF, Cline EJ, Ricaurte GA, Carroll FI, Abraham P, Lewin AH, Kuhar MJ (1992) [123/125I]RTI-55, an in vivo label for the serotonin transporter. Synapse 11:134–139PubMedCrossRefGoogle Scholar
  70. 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: 183–192PubMedCrossRefGoogle Scholar
  71. Schifano F, Di Furia L, Forza G, Minicuci N, Bricolo R (1998) MDMA (‘ecstasy’) consumption in the context of polydrug abuse: a report on 150 patients. Drug Alcohol Depend 52: 85–90PubMedCrossRefGoogle Scholar
  72. Schmidt CJ (1987a) Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine.Google Scholar
  73. J Pharmacol Exp Ther 240: 1–7Google Scholar
  74. Schmidt CJ, Taylor VL (1987b) Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. Biochem Pharmacol 36: 4095–4102PubMedCrossRefGoogle Scholar
  75. Schmidt CJ, Wu L, Lovenberg W (1986) Methylenedioxymethamphetamine: a potentially neurotoxic amphetamine analogue. Eur J Pharmacol 124: 175–178PubMedCrossRefGoogle Scholar
  76. Seiden LS, Fischman MW, Schuster CR (1976) Long-term methamphetamine induced changes in brain catecholamines in tolerant rhesus monkeys. Drug Alcohol Depend 1: 215–219PubMedCrossRefGoogle Scholar
  77. Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, Yoshikawa E, Fatutsubashi M, Takei N, Mori N (2001) Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. Am J Psychiatry 158: 1206–1214PubMedCrossRefGoogle Scholar
  78. 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: 63–69PubMedCrossRefGoogle Scholar
  79. Shulgin A, Shulgin A (1991) Pihkal: a chemical love story. Transform Press, Berkeley, CAGoogle Scholar
  80. Steele TD, Katz JL, Ricaurte GA (1992) Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA). Brain Res 589: 349–352PubMedCrossRefGoogle Scholar
  81. Steele TD, McCann UD, Ricaurte GA (1994) 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans. Addiction 89: 539–551PubMedCrossRefGoogle Scholar
  82. Steranka LR (1983) Long-term effects of a priming dose and short-term infusion of amphetamine on striatal dopamine neurones in rats. Eur J Pharmacol 96: 159–163PubMedCrossRefGoogle Scholar
  83. Steranka LR, Sanders-Bush E (1980) Long-term effects of continuous exposure to amphetamine on brain dopamine concentration and synaptosomal uptake in mice. Eur J Pharmacol 65: 439–443PubMedCrossRefGoogle Scholar
  84. Stone DM, Stahl DC, Hanson GR, Gibb JW (1986) The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. Eur J Pharmacol 128: 41–48PubMedCrossRefGoogle Scholar
  85. Stone DM, Johnson M, Hanson GR, Gibb JW (1987) A comparison of the neurotoxic potential of methylenedioxyamphetamine (MDA) and its N-methylated and N-ethylated derivatives. Eur J Pharmacol 134: 245–248PubMedCrossRefGoogle Scholar
  86. Strote J, Lee JE, Wechsler H (2002) Increasing MDMA use among college students: results of a national survey. J Adolesc Health 30: 64–72PubMedCrossRefGoogle Scholar
  87. Urenjak J, Williams SR, Gadian DG, Noble M (1993) Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci 13: 981–989PubMedGoogle Scholar
  88. Villemagne V, Yuan J, Wong DF, Dannals RF, Hatzidimitriou G, Mathews, Ravert HT, Musachio J, McCann UD, Ricaurte GA (1998) Brain dopamine neurotoxicity in baboons treated with doses of methamphetamine comparable to those recreationally abused by humans: evidence from [11C]WIN-35,428 positron emission tomography studies and direct in vitro determinations. J Neurosci 18: 419–427PubMedGoogle Scholar
  89. Volkow ND, Ding YS, Fowler JS, Wang GJ, Logan J, Gatley SJ, Hitzemann R, Smith G, Fields SD, Gur R (1996) Dopamine transporters decrease with age. J Nucl Med 37: 554–559PubMedGoogle Scholar
  90. Volkow ND, Chang L, Wang G, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding YS, Logan J, Wong C, Miller EN (2001a) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158: 377–382PubMedCrossRefGoogle Scholar
  91. Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, Gatley SJ, Miller E, Hitzemann R, Ding YS, Logan J (2001b) Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 21: 9414–9418PubMedGoogle Scholar
  92. Wagner GC, Ricaurte GA, Seiden LS, Schuster CR, Miller RJ, Westley J (1980) Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine. Brain Res 81: 151–160CrossRefGoogle Scholar
  93. World Health Organization (2001) WHO Expert Committee on Drug Dependence. Thirty-second report. World Health Organ Tech Rep Ser 903: i–v, pp 1-26Google Scholar
  94. Woolverton WL, Cervo L, Johanson CE (1984) Effects of repeated methamphetamine administration on methamphetamine self-adminsitration in rhesus monkeys. Pharmacol Biochem Behav 21: 737–741PubMedCrossRefGoogle Scholar
  95. Zhou FC, Tao-Cheng J, Segu L, Patel T, Wang Y (1998) Serotonin transporters are located on the axons beyond the synaptic junctions: anatomical and functional evidence. Brain Res 805: 241–254PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2003

Authors and Affiliations

  • L. Reneman
    • 1
  1. 1.Department of RadiologyAcademic Medical CenterAmsterdamThe Netherlands

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