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.
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References
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 149:159–163
Bolla KI, McCann UD, Ricaurte GA (1998) Memory impairment in abstinent MDMA (“ecstasy”) users. Neurology 5:1532–1537
Botvinick MM, Braver TS, Barch DM, Carter CS, Cohen JD (2001) Conflict monitoring and cognitive control. Psychol Rev 108:624–652
Buhot MC (1997) Serotonin receptors in cognitive behaviors. Curr Opin Neurobiol 7:243–254
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 241:338–345
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)
Derogatis LR (1994) Symptom Check List-90-R: administration, scoring, and procedures manual. National Computer Systems, Minneapolis
Dughiero G, Schifano F, Forza G (2001) Personality dimension and psychopathological profiles of ecstasy users. Hum Psychopharmacol 16:635–639
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 320:5–8
Fox HC, Toplis AS, Turner JJD, Parrot AC (2001a) Auditory verbal learning in drug free ecstasy polydrug users. Hum Psychopharmacol 16:613–618
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 15:273–281
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 162:203–214
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 9:110–119
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 47:127–136
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 76:316–321
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 68:719–725
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 38:404–411
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.
Holroyd CB, Coles MGH (2002) The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity. Psychol Rev 109:679–730
Hunter AJ (1989) Serotonergic involvement in learning and memory. Biochem Soc Transact 17:79–81
Larson GE, Merritt CR, Williams SE (1998) Information processing and intelligence: some implications of task complexity. Intelligence 12:131–147
Liechti ME, Gamma A, Vollenweider FX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology 154:161–168
McCann UD, Ridenour A, Shaman Y, Ricaurte GA (1994) Serotonin neurotoxicity after 3,4-nethylenedioxymethylamfetamine (MDMA; “ecstasy”): a controlled study in humans. Neuropsychopharmacology 10:129–138
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 352:1433–1437
McCann UD, Mertl M, Eligulashvili V, Ricaurte GA (1999) Cognitive performance in 3,4-methylenedioxymethylamfetamine (MDMA, “ecstasy”) users: a controlled study. Psychopharmacology 143:417–425
Milani R, Schifano F (2000) Neuropsychological problems associated with ecstasy use. J Psychopharmacol 14:14
Milner B (1971) Interhemispheric differences in the localization of psychological processes in man. Br Med Bull 27:272–277
Mittenberg W, Motta S (1993) Effects of cocaine abuse on memory and learning. Arch Clin Neuropsychol 8:477–484
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 41:49–100
Mokler DJ, Robinson SE, Rosecrans JA (1987) 3,4-Methylenedioxymethylamphetamine (MDMA) produces long-term reductions in brain 5-hydroxytrytamine in rats. Eur J Pharmacol 138:265–268
Morgan MJ (1998) Recreational use of “ecstasy” (MDMA) is associated with elevated impulsivity. Neuropsychopharmacology 19:252–264
Morgan MJ (1999) Memory deficits associated with recreational use of “ecstasy” (MDMA). Psychopharmacology 141:30–36
Morgan MJ (2000) Ecstasy: a review of its persistent psychological effects. Psychopharmacology 152:230–248
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 23:113–126
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 40:65–74
Pan HS, Wang RY (1990) The action of MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system. Brain Res 543:56–60
Parrot AC, Sisk E, Turner JJD (2000) Psychobiological problems in heavy “ecstasy” (MDMA) polydrug users. Drug Alcohol Depend 60:105–110
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 385:1864–1869
Ricaurte GA, McCann UD (1992) Neurotoxic amphetamine analogues: effects in monkeys and implications for humans. Ann N Y Acad Sci 371–382
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 112–113:143–146
Ridderinkhof KR, van der Molen MW (1995) A psychophysiological analysis of developmental differences in the ability to resist interference. Child Dev 66:1040–1056
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 101:315–337
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 298:2209–2211
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 49:382–401
Rosselli M, Ardila A (1996) Cognitive effects of cocaine and polydrug abuse. J Clin Exp Neuropsychol 18:122–135
Schmidt CJ, Wu L, Lovenberg W (1986) Methylenedioxymethylamphetamine: a potentially neurotoxic amphetamine analogue. Eur J Pharmacol 124:175–178
Schnirman GM, Welsh MC, Retzlaff PD (1998) Development of the Tower of London—revised. Assessment 5:355–360
Schwartz RH, Grueneweld PJ, Klitzner M, Fedio P (1989) Short term memory impairments in cannabis-dependent adolescents. Am J Disord Child 143:1214–1219
Shallice T (1982) Specific impairments in planning. Philos Trans R Soc Lond Series B 298:199–209
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 58:229–262
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 161:23–31
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 153:196–202
Wareing M, Fisk JE, Murphy PN (2000) Working memory deficits in current and previous users of MDMA (“ecstasy”). Br J Psychol 91:181–188
Zakzanis KK, Young DA (2001a) Memory impairment in abstinent MDMA (“ecstasy”) users: a longitudinal investigation. Neurology 56:966–969
Zakzanis KK, Young DA (2001b) Executive function in abstinent MDMA (“ecstasy”) users. Med Sci Monit 7:1292–1298
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Alting von Geusau, N., Stalenhoef, P., Huizinga, M. et al. Impaired executive function in male MDMA (“ecstasy”) users. Psychopharmacology 175, 331–341 (2004). https://doi.org/10.1007/s00213-004-1832-8
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DOI: https://doi.org/10.1007/s00213-004-1832-8