Cerebral activation in abstinent ecstasy (MDMA) users during a working memory task: a functional magnetic resonance imaging (fMRI) study. Memory impairment in abstinent MDMA (“Ecstasy”) users: A longitudinal investigation Cognitive performance and serotonergic function in users of ecstasy Psychological and Cardiovascular Effects and Short-Term Sequelae of MDMA (“Ecstasy”) in MDMA-Naïve Healthy Volunteers Neural correlates of working memory in pure and polyvalent ecstasy (MDMA) users Incidental use of ecstasy: no evidence for harmful effects on cognitive brain function in a prospective fMRI study Recreational Use of “Ecstasy” (MDMA) Is Associated with Elevated Impulsivity Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study Prospective memory, everyday cognitive failure and central executive function in recreational users of Ecstasy. Memory-related hippocampal functioning in ecstasy and amphetamine users How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale Mood disorders and serotonin transporter density in ecstasy users—the influence of long-term abstention, dose, and gender Cognitive function and mood in MDMA/THC users, THC users and non-drug using controls Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users. A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance. Ecstasy use: cognitive deficits related to dosage rather than self-reported problematic use of the drug
The popular recreational drug ecstasy ( 3,4-methylenedioxymethamphetamine = MDMA and related congeners ) is neurotoxic upon central serotonergic systems in animal studies . So far , the most convincing evidence for neurotoxicity-related functional deficits in humans derives from neurocognitive studies demonstrating dose-related long-term learning and memory problems in ecstasy users . In our study we used functional magnetic resonance imaging ( fMRI ) and a working memory task to investigate cerebral activation in eleven heavy , but currently abstinent MDMA users and two equally sized groups of moderate users and non-users . There were no significant group differences in working memory performance and no differences in cortical activation patterns for a conservative level of significance . However , for a more liberal statistical criterion , both user groups showed stronger activations than controls in right parietal cortex . Furthermore , heavy users had a weaker blood oxygenation level-dependent ( BOLD ) response than moderate users and controls in frontal and temporal areas . Our results may indicate subtle altered brain functioning associated with prior MDMA use , although alternative interpretations of these group differences must be considered To examine the neurotoxic potential of continued  MDMA ( “ Ecstasy ” )  use in humans and its functional consequences over the course of 1 year , 15 MDMA users participated in a longitudinal study in which they completed a brief neuropsychological test battery composed mainly of retrospective and prospect i ve memory tasks . Subjects were abstinent for 2 weeks on initial and 1-year testing . Continued use of MDMA was associated with progressive decline in terms of immediate and delayed recall Abstract . Rationale : ( ± ) 3,4-Methylenedioxymethamphetamine ( MDMA or " ecstasy " ) has been shown to cause long term damage to serotonergic cerebral neurons in animals . The neurotoxic effects in humans are less clear and little is known about the functional consequences , although some studies suggest memory impairment . Given the widespread use of MDMA , our lack of knowledge raises concerns . Objective : We investigated , in humans , the relation between past use of ecstasy and cognitive performance as well as serotonergic function . Methods : Two groups of 21 males with moderate and heavy recreational use of MDMA , respectively , and a control group of 20 males without use of MDMA were compared . All were from the same subculture . Reaction time , direct recall , and recognition were assessed . Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled , crossover challenge with dexfenfluramine . Results : Ecstasy users showed a broad pattern of statistically significant , but clinical ly small , impairment of memory and prolonged reaction times . Heavy users were affected stronger than moderate users . Release of cortisol but not of prolactin  after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls . Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy , psychosocial profiles and use of other drugs did not explain the differences found between the groups . Conclusions : These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function . These findings are compatible with neurotoxicity of ecstasy as shown in animals 3,4-methylenedioxymethamphetamine ( MDMA , “ Ecstasy ” ) is a recreational drug reported to produce a different psychological profile than that of classic hallucinogens and stimulants . It has , therefore , been tentatively classified into a novel pharmacological class termed entactogens . This double-blind placebo-controlled study examined the effects of a typical recreational dose of MDMA ( 1.7 mg/kg ) in 13 MDMA-naıuml;ve healthy volunteers .  MDMA produced an affective state of enhanced mood , well-being , and increased emotional sensitiveness , little anxiety , but no hallucinations or panic reactions . Mild depersonalization and derealization phenomena occurred together with moderate thought disorder , first signs of loss of body control , and alterations in the meaning of percepts . Subjects also displayed changes in the sense of space and time , heightened sensory awareness , and increased psychomotor drive .  MDMA did not impair selective attention as measured by the Stroop test . MDMA  increased blood pressure moderately , with the exception of one subject who showed a transient hypertensive reaction . This severe increase in blood pressure indicates that the hypertensive effects of MDMA , even at recreational doses , should not be underestimated , particularly in subjects with latent cardiovascular problems . Most frequent acute somatic complaints during the MDMA challenge were jaw clenching , lack of appetite , impaired gait , and restless legs . Adverse sequelae during the following 24 hours included lack of energy and appetite , feelings of restlessness , insomnia , jaw clenching , occasional difficulty concentrating , and brooding . The present findings are consistent with the hypothesis that MDMA produces a different psychological profile than classic hallucinogens or psychostimulants Poor cognitive performance in ecstasy ( 3,4-methylenedioxymethamphetamine ; MDMA ) users has been related to the well-recognized neurotoxic effects of the drug upon central serotonergic and possibly also dopaminergic systems . However , concomitant use of other drugs has been a critical confound in most investigations . In this study we used an n-back task and fMRI to investigate working memory performance and related cerebral activation in eight , currently abstinent pure MDMA users and two matched groups of polyvalent MDMA users and non-users . Pure MDMA users presented lower activations than controls and /or polyvalent users , most notably in inferior temporal regions , the angular gyrus and the striate cortex , whereas polyvalent users did not differ from controls . Our results suggest that altered brain activation patterns during cognitive processing in ecstasy users may be mainly associated with prior MDMA use . Concomitant use of other drugs may modify this effect Rationale Heavy ecstasy use in humans has been associated with cognitive impairments and changes in cognitive brain function supposedly due to damage to the serotonin system . There is concern that even a single dose of 3,4-methylenedioxymethamphetamine may be neurotoxic , but very little is known about the consequences of a low dose of ecstasy for cognitive brain function . Objectives The objective of the study was to assess the effects of a low dose of ecstasy on human cognitive brain function using functional magnetic resonance imaging ( fMRI ) . Material s and method We prospect ively studied , as part of the NeXT ( Netherl and s XTC toxicity ) study , sustained effects of a low dose of ecstasy on brain function in 25 subjects before and after their first episode of ecstasy use ( mean 2.0 ± 1.4 ecstasy pills , on average 11.1 ± 12.9 weeks since last ecstasy use ) , compared to 24 persistent ecstasy-naive controls , also measured twice and matched with the novice users on age , gender , IQ , and cannabis use .  Cognitive brain function was measured in the domains of working memory , selective attention , and associative memory using fMRI . Results No significant effects were found of a low dose of ecstasy on working memory , selective attention , or associative memory neither at the behavioral level nor at the neurophysiological level . Conclusions This study yielded no firm evidence for sustained effects of a low dose of ecstasy on human cognitive brain function . The present findings are relevant for the development of prevention and harm reduction strategies . Furthermore , the study is relevant to the discussion concerning potential therapeutic use of ecstasy Recent pre clinical evidence suggests that repeated exposure to 3 , 4-methylenedioxy-methamphetamine ( MDMA ; “ ecstasy ” ) produces long-term reductions in serotonin ( 5-HT ) levels . 5-HT has been implicated in the regulation of mood , anxiety , aggression , impulsivity , and cognition . Accordingly , in the first of two separate studies , these variables were investigated in three groups : ( 1 ) MDMA group — recreational ecstasy users ( who also used other illicit substances ) ; ( 2 ) polydrug controls — who had never taken ecstasy , but otherwise had drug histories and personal characteristics similar to the ecstasy users ; and ( 3 ) nondrug controls — who had never used illicit drugs , but had similar personal characteristics . All participants completed mood ( Likert ) scales , personality question naires ( which included the impulsiveness , venturesomeness and empathy question naire – IVE ) , spatial span and “ Tower of London ” ( TOL ) tests , and a behavioural measure of impulsivity , the matching familiar figures test ( MFF20 ) . There were no group differences in mood , anxiety , anger/hostility , and cognitive performance , but the MDMA group committed significantly more errors in the MFF20 . Subsequently , a larger sample of participants were administered mood ( the General Health Question naire or GHQ ) and personality ( IVE ) question naires before the administration of a TOL test , followed by the MFF20 , and a second TOL test . Although there were no group differences in TOL performance , ecstasy users were again found to commit more errors in the MFF20 than polydrug users . Furthermore , the GHQ and IVE scores of the ecstasy users in the second study indicated , respectively , that they were more psychologically disturbed and impulsive than nondrug controls . The combined data from the two studies indicated that ecstasy users exhibited elevated impulsivity on both self-report and behavioral measures and that those who had taken the most ecstasy had the most elevated trait impulsiveness scores . These findings are consistent with previous evidence that elevated levels of impulsivity in humans are associated with reduced levels of serotonergic function 3,4-Methylenedioxymethamphetamine ( MDMA ) is associated with changes in neurocognitive performance . Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis . However , results from animal research need to be applied to humans with caution . Moreover , several of the studies that examine  MDMA users suffer from method ological shortcomings . Therefore , a prospect i ve cohort study was design ed in order to overcome these previous method ological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users . It was hypothesized that , depending on the amount of MDMA taken , the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance , especially in visual paired association learning tasks . Ninety-six subjects were assessed , at the second follow-up assessment : 31 of these were non-users , 55 moderate-users , and 10 heavy-users . Separate repeated measures analyses of variance were conducted for each cognitive domain , including attention and information processing speed , episodic memory , and executive functioning . Furthermore , possible confounders including age , general intelligence , cannabis use , alcohol use , use of other concomitant substances , recent medical treatment , participation in sports , level of nutrition , sleep patterns , and subjective well-being were assessed . The Repeated measures analysis of variance ( rANOVA ) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years . No further deterioration in continuing MDMA-users  was observed in the second follow-up period . No significant differences with the other neuropsychological tests were noted . It seems that MDMA use can impair visual paired associates learning in new users . However , the groups differed in their use of concomitant use of illicit drugs . Therefore , performance differences between the groups can not completely ascribed to the use of MDMA Chronic use of MDMA ( 3,4-methylenedioxymethamphetamine ) , or Ecstasy , is believed to lead to impaired psychological performance , including well-documented decrements in laboratory and field tests of retrospective memory . Less is known about the impact of Ecstasy on aspects of ' everyday ' memory , despite obvious concerns about such effects . The three studies reported here focused on the impact of chronic Ecstasy use on prospect i ve memory ( PM ) , associated central executive function and other aspects of day-to-day cognition . In study 1 46 regular Ecstasy users were compared with 46 Ecstasy-free controls  using the  Prospect i ve Memory Question naire ( PMQ ) . Ecstasy users reported significantly more errors in PM ( remembering to do something in the future ) ; these findings persisted after controlling for other drug use and the number of strategies used to aid memory . No difference was found between representative subgroups on the Lies Scale of the Eysenck Personality Question naire . In study 2 a different group of 30 regular Ecstasy users and 37 Ecstasy-free controls was assessed on the PMQ and on a central executive task comprising verbal fluency measures . The results confirmed the significant impairments in long- and short-term PM and revealed corresponding impairments in verbal fluency . In study 3 15 Ecstasy users , 15 cannabis users and 15 non-drug users were assessed using the  Cognitive Failures Question  naire , which requires participants to provide ratings of the frequency of various day-to-day cognitive slips . The results indicate that the Ecstasy users did not perceive their general cognitive performance to be worse than that of controls . Taken together , these results suggest that Ecstasy users have impaired PM that can not be explained by an increased propensity to exaggerate cognitive failures . These may be attributable , in part , to central executive deficits that are due to frontal lobe damage associated with Ecstasy use . Copyright 2001 John Wiley & Sons , Rationale Recreational use of ecstasy ( 3,4-methylenedioxymethamphetamine [ MDMA ] ) has been associated with memory impairments . Functional neuroimaging studies with cross-sectional design s reported altered memory-related hippocampal functioning in ecstasy-polydrug users . However , differences might be pre-existing or related to the concomitant use of amphetamine . Objective To prospect ively investigate the specific effects of ecstasy on memory-related hippocampal functioning . Methods We used an associative memory task and functional magnetic resonance imaging ( fMRI ) in 40 ecstasy and /or amphetamine users at baseline ( t1 ) and after 12 months ( t2 ) . At t1 , all subjects had very limited amphetamine and /or ecstasy experience ( less than 5 units lifetime dose ) . Based on the reported drug use at t2 , subjects with continued ecstasy and /or amphetamine use ( n = 17 ) were compared to subjects who stopped use after t1 ( n = 12 ) . Results Analysis of repeated measures revealed that encoding-related activity in the left parahippocampal gyrus changed differentially between the groups . Activity in this region increased in abstinent subjects from t1 to t2 , however , decreased in subjects with continued use . Decreases within the left parahippocampal gyrus were associated with the use of ecstasy , but not amphetamine , during the follow-up period . However , there were no significant differences in memory performance . Conclusions The current findings suggest specific effects of ecstasy use on memory-related hippocampal functioning . However , alternative explanations such as (sub-)acute cannabis effects are conceivable Abstract Exposure therapy is known to be an effective treatment for anxiety disorders . Nevertheless , exposure is not used as much as it should be , and instead patients are often given supportive medications such as serotonin reuptake inhibitors ( SSRIs ) and benzodiazepines , which may even interfere with the extinction learning that is the aim of treatment . Given that r and omized controlled trials are now investigating a few doses of ±3,4-methylenedioxymethamphetamine ( MDMA , ‘ ecstasy ’ ) in combination with psychotherapy for treatment-resistant anxiety disorders , we would like to suggest the following three mechanisms for this potentially important new approach : 1 ) MDMA  increases oxytocin levels , which may strengthen the therapeutic alliance ; 2 ) MDMA  increases ventromedial prefrontal activity and decreases amygdala activity , which may improve emotional regulation and decrease avoidance and 3 ) MDMA  increases norepinephrine release and circulating cortisol levels , which may facilitate emotional engagement and enhance extinction of learned fear associations . Thus , MDMA has a combination of pharmacological effects that , in a therapeutic setting , could provide a balance of activating emotions while feeling safe and in control , as described in case reports of MDMA-augmented psychotherapy . Further clinical and pre clinical studies of the therapeutic value of MDMA are indicated Rationale Neurotoxic effects of 3,4-methylenedioxymethamphetamine ( MDMA , “ ecstasy ” ) on the serotonin ( 5-HT ) system have been described in animals and humans , but little is known about long-term effects of ecstasy use on mood . Objectives To investigate short-term and long-term effects of ecstasy use on mood and its association with 5-HT neurotoxicity , dose , and gender in humans . Methods Fifteen moderate ecstasy users , 23 heavy ecstasy users , 16 former heavy ecstasy users and 15 drug-using , but ecstasy-naive controls were included .  Mood was assessed using the Composite International Diagnostic Interview ( CIDI ) and the Beck Depression Inventory ( BDI ) . Outcomes were correlated with 5-HT transporter ( SERT ) density , assessed with [123I]β-CIT single photon emission computed tomography ( SPECT ) . Results The prevalence of mood disorders assessed by CIDI did not differ between all groups . The overall test for differences in BDI scores between groups was near significance ( P=0.056 ) , with BDI scores higher in former heavy ecstasy users than in ecstasy-naive controls ( P=0.045 ) . BDI scores were correlated with the total number of ecstasy tablets used ( r=0.310 ; P=0.021 ) . No associations between CIDI or BDI outcomes and SERT density or gender were observed . Conclusions These results suggest that ecstasy use is not associated with clinical depression ( CIDI ) . However , the number of ecstasy tablets taken lifetime was associated with higher BDI scores for depressive mood , and this relationship seemed to persist after ecstasy use had stopped . We did not find that depressed mood in ecstasy users was associated with decrease in SERT density . Prospect i ve studies are needed to establish the causal relationship between ecstasy use and depressed mood Repeated ecstasy ( MDMA ) use is reported to impair cognition and cause increased feelings of depression and anxiety . Yet , many relevant studies have failed to control for use of drugs other than MDMA , especially marijuana ( THC ) . To address these confounding effects we compared behavioural performance of 11 MDMA/THC users , 15 THC users and 15 non-drug users matched for age and intellect . We tested the hypothesis that reported feelings of depression and anxiety and cognitive impairment ( memory , executive function and decision making ) are more severe in MDMA/THC users than in THC users . MDMA/THC users reported more intense feelings of depression and anxiety than THC users and non-drug users . Memory function was impaired in both groups of drug users . MDMA/THC users showed slower psychomotor speed and less mental .exibility than non-drug users . THC users exhibited less mental .exibility and performed worse on the decision making task compared to non-drug users but these functions were similar to those in MDMA/THC users . It was concluded that MDMA use is associated with increased feelings of depression and anxiety compared to THC users and non-drug users . THC users were impaired in some cognitive abilities to the same degree as MDMA/THC users , suggesting that some cognitive impairment attributed to MDMA is more likely due to concurrent THC use Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain . However , it can not be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use . As part of the Netherl and s XTC Toxicity ( NeXT ) study , we prospect ively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity . At baseline , 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined . After a mean period of 17 months follow-up , neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared . Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane ( CIT ) SPECT to measure serotonin transporter densities as indicators of serotonergic function ; (1)H-MR spectroscopy ( (1)H-MRS ) to measure brain metabolites as indicators of neuronal damage ; diffusion tensor imaging ( DTI ) to measure the apparent diffusion coefficient and fractional anisotropy ( FA ) of the diffusional motion of water molecules in the brain as indicators of axonal integrity ; and perfusion weighted imaging ( PWI ) to measure regional relative cerebral blood volume ( rrCBV ) which indicates brain perfusion . With this approach , both structural ( (1)H-MRS and DTI ) and functional ( [(123)I]beta-CIT SPECT and PWI ) aspects of neurotoxicity were combined . Compared to persistent ecstasy-naives , novel low-dose ecstasy users ( mean 6.0 , median 2.0 tablets ) showed decreased rrCBV in the globus pallidus and putamen ; decreased FA in thalamus and frontoparietal white matter ; increased FA in globus pallidus ; and increased apparent diffusion coefficient in the thalamus . No changes in serotonin transporter densities and brain metabolites were observed . These findings suggest sustained effects of ecstasy on brain microvasculature , white matter maturation and possibly axonal damage due to low dosages of ecstasy . Although we do not know yet whether these effects are reversible or not , we can not exclude that ecstasy even in low doses is neurotoxic to the brain It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use . We prospect ively studied sustained effects ( > 2 weeks abstinence ) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report question naires on psychopathology as part of the NeXT ( Netherl and s XTC Toxicity ) study . Outcomes of  proton magnetic resonance spectroscopy ( 1H-MRS ) , diffusion tensor imaging ( DTI ) , perfusion-weighted imaging ( PWI ) , and question naires on depression , impulsivity , and sensation seeking were compared in 30 subjects ( 12 M , 21.8±3.1 years ) in two sessions before and after first ecstasy use ( 1.8±1.3 tablets ) . Interval between baseline and follow-up was on average 8.1±6.5 months and time between last ecstasy use and follow-up was 7.7±4.4 weeks . Using 1H-MRS , no significant changes were observed in metabolite concentrations of N-acetylaspartate ( NAA ) , choline ( Cho ) , myo-inositol ( mI ) , and creatine ( Cr ) , nor in ratios of NAA , Cho , and mI relative to Cr . However , ecstasy use was followed by a sustained 0.9 % increase in fractional anisotropy ( FA ) in frontoparietal white matter , a 3.4 % decrease in apparent diffusion ( ADC ) in the thalamus and a sustained decrease in relative regional cerebral blood volume ( rrCBV ) in the thalamus ( −6.2 % ) , dorsolateral frontal cortex ( −4.0 % ) , and superior parietal cortex ( −3.0 % ) ( all significant at p<0.05 , paired t-tests ) . After correction for multiple comparisons , only the rrCBV decrease in the dorsolateral frontal cortex remained significant . We also observed increased impulsivity ( + 3.7 % on the Barratt Impulsiveness Scale ) and decreased depression ( −28.0 % on the Beck Depression Inventory ) in novel ecstasy users , although effect sizes were limited and clinical relevance question able . As no indications were found for structural neuronal damage with the currently used techniques , our data do not support the concern that incidental ecstasy use leads to extensive axonal damage . However , sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas , although it is not known whether this effect is permanent . Additional studies are needed to replicate these findings This paper describes the objectives and methods of The Netherl and s XTC Toxicity ( NeXT ) study focussing on the causality , course , and clinical relevance of ecstasy neurotoxicity . Previous studies suggest that ecstasy ( 3,4 methylene-dioxymethamphetamine , MDMA , XTC ) is toxic toward brain serotonin axons , but most of these studies have serious method ological limitations . The current study is a combination of different approaches with three sub studies : ( 1 ) a crosssectional sub study among heavy ecstasy users and controls with variation in drug use , which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs ; ( 2 ) a prospect i ve cohort sub study in ecstasy-naive subjects with high risk for future ecstasy use , which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity , and ( 3 ) a retrospective cohort sub study in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population . Neurotoxicity is studied using ( a ) different imaging techniques ( beta-CIT SPECT , 1H-MR spectroscopy , diffusion tensor imaging , perfusion weighted imaging and functional magnetic resonance imaging ) , and ( b ) neuropsychological and psychiatric assessment s of memory , depression , and personality . The combined results will lead to conclusions that can be used in prevention messages , clinical decision making , and the development of an (inter)national ecstasy policy Previous research has shown drug-free Ecstasy users to demonstrate selective cognitive impairment However , there seems to be a degree of individual variation in the occurrence of such deficits . The present study aim ed to assess whether these cognitive deficits are related to an awareness of problematic Ecstasy use , or to past drug dosage . Twenty regular Ecstasy users who reported experiencing Ecstasy-related problems were compared with 20 Ecstasy users who had not reported any previous problems . The two groups displayed similar past histories in relation to a range of illicit drugs , and were divided into low , medium and high users . The controls comprised 20 illicit recreational drug users who had never taken Ecstasy . Executive task measures comprised the  Tower of London ( TOL ) , the Wisconsin Card Sorting Task ( WCST ) and spatial working memory . Immediate and delayed word recall , matched verbal recognition and recall and simple reaction time were also included . Both Ecstasy groups performed significantly worse than controls on two executive measures : TOL planning time and spatial working memory score . There were no differences in cognitive impairment between the Ecstasy users who complained of problems and those who did not . In both groups , decrement on executive tasks was demonstrated as a function of previous drug dose . The study confirms that heavy Ecstasy polydrug use may culminate in selective executive deficits . It also demonstrates that two differently self-perceived Ecstasy groups showed similar cognitive impairment , despite only one group complaining of problems . Because all Ecstasy participants also consumed a range of other illicit drugs , the results are reflective of Ecstasy polydrug use in individuals who use Ecstasy as a drug of preference
There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures .
MDMA ( " ecstasy " ) is widely used as a recreational drug , although there has been some debate about its neurotoxic effects in humans .
However , most studies have investigated subjects with heavy use patterns , and the effects of transient MDMA use are unclear .
In this review , we therefore focus on subjects with moderate use patterns , in order to assess the evidence for harmful effects .