title: Thermoregulatory effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans Memory-related hippocampal functioning in ecstasy and amphetamine users Smaller amygdala and medial prefrontal cortex predict escalating stimulant use. Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users. Mood disorders and serotonin transporter density in ecstasy users—the influence of long-term abstention, dose, and gender Use, abuse and dependence of ecstasy and related drugs in adolescents and young adults-a transient phenomenon? Results from a longitudinal community study. The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users Ecstasy use: cognitive deficits related to dosage rather than self-reported problematic use of the drug The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance. Gender differences in the subjective effects of MDMA 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 Cerebral activation in abstinent ecstasy (MDMA) users during a working memory task: a functional magnetic resonance imaging (fMRI) study. Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD)
abstract: Rationale Although 3,4-methylenedioxymethamphetamine ( MDMA ; Ecstasy ) has been reported to cause fatal hyperthermia , few studies of the effects of MDMA on core body temperature in humans have been conducted demonstrating increased body temperature . In rats , MDMA causes hyperthermia at warm ambient temperatures but hypothermia at cold ones . Objectives In this study , the physiological and subjective effects of MDMA in humans were determined at cold ( 18 ° C ) and warm ( 30 ° C ) ambient temperatures in a temperature and humidity-controlled laboratory . Methods Ten healthy volunteers who were recreational users of MDMA were recruited . Four laboratory sessions were conducted in a 2 × 2 design [ i.e. , two sessions at 30 ° C and two at 18 ° C , two during MDMA ( 2 mg/kg , p.o . ) and two during placebo , in double-blind fashion ] . Core body temperature ( ingested radiotelemetry pill ) , skin temperature ( four weighted sites ) , heart rate , blood pressure , metabolic rate ( indirect calorimetry ) , shivering ( electromyogram levels ) , and sweat rate ( capacitance hygrometry ) were measured as well as subjective effects for several time periods following capsule ingestion . Results MDMA produced significant elevations in core body temperature and metabolic rate in both warm and cold conditions . MDMA also produced significant elevations in blood pressure and heart rate and significantly increased several ratings of subjective effects similar to those previously reported . There were no differences related to ambient temperature for any of the subjective effects , except that ratings of cold and warm were appropriate to the ambient temperature and were not influenced by MDMA . Conclusions Unlike findings in rats , MDMA  increased core body temperature regardless of ambient temperature in humans . These increases appeared related to increases in metabolic rate , which were substantial . These findings warrant further investigations on the role of MDMA and other stimulants in altering metabolism and thermogenesis 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 Drug addiction is a chronic , relapsing brain disorder . The identification of biomarkers that render individuals vulnerable for the transition from occasional drug use to addiction is of key importance to develop early intervention strategies . The aim of the present study was to prospect ively assess brain structural markers for escalating drug use in two independent sample s of occasional amphetamine-type stimulant users . At baseline occasional users of amphetamine and 3,4-methylenedioxymethamphetamine ( cumulative lifetime use ≤10 units ) underwent structural brain imaging and were followed up at 12 months and 24 months ( Study 1 , n = 38 ; Study 2 , n = 28 ) . Structural vulnerability markers for escalating amphetamine-type drug use were examined by comparing baseline grey matter volumes of participants who increased use with those who maintained or reduced use during the follow-up period . Participants in both sample s who subsequently increased amphetamine-type drugs use displayed smaller medial prefrontal cortex volumes and , additionally , in the basolateral amygdala ( Study 1 ) and dorsal striatum ( Study 2 ) . In both sample s the baseline volumes were significantly negatively correlated with stimulant use during the subsequent 12 and 24 months . Additional multiple regression analyses on the pooled data sets revealed some evidence of a compound-specific association between the baseline volume of the left basolateral amygdala and the subsequent use of amphetamine . These findings indicate that smaller brain volumes in fronto-striato-limbic regions implicated in impulsivity and decision-making might render an individual vulnerable for the transition from occasional to escalating amphetamine-type stimulant 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 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 OBJECTIVE To determine incidence and patterns of natural course of ecstasy/stimulant/hallucinogen ( ESH ) use and disorders as well as cohort effects in a community sample of adolescents and young adults . METHOD Cumulative incidence and patterns of ecstasy use and disorders were examined in a prospect i ve longitudinal design ( mean follow-up period=42 months ) in a representative sample ( N=2446 ) aged 14 - 24 years at the outset of the study . Patterns of DSM-IV defined ESH use , abuse and dependence were assessed with the Munich Composite International Diagnostic Interview ( M-CIDI ) . RESULTS ( 1 ) Cumulative lifetime incidence for use of ESH at second follow-up : 9.1 % , 1.0 % for abuse , 0.6 % for dependence ; ( 2 ) men used and abused ESH more often than women ; ( 3 ) the younger birth cohort ( 1977 - 81 ) tended to start earlier with substance (ab)use compared to the older birth cohort ( 1970 - 77 ) ; ( 4 ) use of ESH was associated with increasing rates of concomitant use of other licit and illicit drugs ; ( 5 ) the majority of the lifetime ESH users without disorder had stopped to use these substances and not consumed them during the 12 months preceding the second follow-up ; ( 6 ) those who had stopped to take ecstasy and related drugs at follow-up also took other illicit drugs  less often than those who continued to consume ESH . CONCLUSIONS Use of design er drugs is widespread in our sample , but the probability of developing use disorders is fairly low ( 1.6 % ) . The majority of the ESH users stopped their use spontaneously in their twenties ( 80 % of the prior users without disorder , 67 % of the prior abusers ) , but 50 % of those that once had fulfilled DSM-IV criteria of dependence continued to use these substances Case reports indicate that psychiatrists administered ±3,4-methylenedioxymethamphetamine ( MDMA ) as a catalyst to psychotherapy before recreational use of MDMA as ‘ Ecstasy ’ result ed in its criminalization in 1985 . Over two decades later , this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct . Twenty patients with chronic posttraumatic stress disorder , refractory to both psychotherapy and psychopharmacology , were r and omly assigned to psychotherapy with concomitant active drug ( n = 12 ) or inactive placebo ( n = 8) administered during two 8-h experimental psychotherapy sessions . Both groups received preparatory and follow-up non-drug psychotherapy . The primary outcome measure was the Clinician-Administered PTSD Scale , administered at baseline , 4 days after each experimental session , and 2 months after the second session . Neurocognitive testing , blood pressure , and temperature monitoring were performed . After 2-month follow-up , placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA .  Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline . The rate of clinical response was 10/12 ( 83 % ) in the active treatment group versus 2/8 ( 25 % ) in the placebo group . There were no drug-related serious adverse events , adverse neurocognitive effects or clinical ly significant blood pressure increases . MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm , and it may be useful in patients refractory to other treatments 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 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 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 Abstract . Rationale : 3,4-Methylenedioxymethamphetamine ( MDMA ) mainly releases serotonin ( 5-HT ) and is contained in the recreational drug Ecstasy . 5-HT is known to play an important role in mood and anxiety disorders , for which there is a female preponderance . To date , there are no systematic data on gender differences in the subjective effects of MDMA . Objectives : The present work analyzed the pooled data from three controlled studies on the psychological and physiological effects of MDMA in healthy volunteers with no or minimal MDMA experience . A particular focus of the analyses were possible gender differences . Methods : A total of 74 subjects ( 54 male , 20 female ) participated in all three studies .  MDMA in oral doses ranging from 70–150 mg ( 1.35–1.8 mg/kg ) was administered under double-blind placebo-controlled conditions . Subjective peak changes were assessed by st and ardized psychometric rating scales . Physiological measures were blood pressure , heart rate , and peripheral body temperature . Adverse drug effects were assessed during the experimental session and after 24 h. Results : Psychoactive effects of MDMA were more intense in women than in men . Women especially had higher scores for  MDMA-induced perceptual changes , thought disturbances , and fear of loss of body control . The dose of MDMA positively correlated with the intensity of perceptual changes in women . Acute adverse effects and sequelae were also more frequent in female than in male subjects . In contrast , men showed higher increases in blood pressure than woman . Conclusions : The fact that equal doses of MDMA per kilogram body weight produce stronger responses in women compared to men is consistent with an increased susceptibility of women to the 5-HT-releasing effects of MDMA . Our results also indicate that increasing doses of MDMA produce more hallucinogen-like perceptual alterations , particularly in women 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 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 BACKGROUND After no research in humans for > 40 years , there is renewed interest in using lysergic acid diethylamide ( LSD ) in clinical psychiatric research and practice . There are no modern studies on the subjective and autonomic effects of LSD , and its endocrine effects are unknown . In animals , LSD disrupts prepulse inhibition ( PPI ) of the acoustic startle response , and patients with schizophrenia exhibit similar impairments in PPI . However , no data are available on the effects of LSD on PPI in humans . METHODS In a double-blind , r and omized , placebo-controlled , crossover study , LSD ( 200 μg ) and placebo were administered to 16 healthy subjects ( 8 women , 8 men ) . Outcome measures included psychometric scales ; investigator ratings ; PPI of the acoustic startle response ; and autonomic , endocrine , and adverse effects . RESULTS Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours . The predominant effects induced by LSD  included visual hallucinations , audiovisual synesthesia , and positively experienced derealization and depersonalization phenomena . Subjective well-being , happiness , closeness to others , openness , and trust were increased by LSD . Compared with placebo , LSD  decreased PPI  . LSD significantly increased blood pressure , heart rate , body temperature , pupil size , plasma cortisol , prolactin , oxytocin , and epinephrine . Adverse effects produced by LSD completely subsided within 72 hours . No severe acute adverse effects were observed . CONCLUSIONS In addition to marked hallucinogenic effects , LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy . LSD altered sensorimotor gating in a human model of psychosis , supporting the use of LSD in translational psychiatric research . In a controlled clinical setting , LSD can be used safely , but it produces significant sympathomimetic stimulation Psychiatrists and psychotherapists in the US ( 1970s to 1985 ) and Switzerl and ( 1988–1993 ) used MDMA legally as a prescription drug , to enhance the effectiveness of psychotherapy . Early reports suggest that it is useful in treating trauma-related disorders . Recently , the first completed pilot study of MDMA-assisted psychotherapy for PTSD yielded encouraging results . Design ed to test the safety and efficacy of MDMA-assisted psychotherapy in patients with treatment-resistant PTSD ; our r and omized , double-blind , active-placebo controlled trial enrolled 12 patients for treatment with either low-dose ( 25 mg , plus 12.5 mg supplemental dose ) or full-dose MDMA ( 125 mg , plus 62.5 mg supplemental dose ) .  MDMA was administered during three experimental sessions , interspersed with weekly non-drug-based psychotherapy sessions . Outcome measures used were the Clinician-Administered PTSD Scale ( CAPS ) and the Posttraumatic Diagnostic Scale ( PDS ) . Patients were assessed at baseline , three weeks after the second and third MDMA session ( end of treatment ) , and at the 2-month and 1-year follow-ups . We found that MDMA-assisted psychotherapy can be safely administered in a clinical setting . No drug-related serious adverse events occurred . We did not see statistically significant reductions in CAPS scores ( p = 0.066 ) , although there was clinical ly and statistically significant self-reported ( PDS ) improvement ( p = 0.014 ) . CAPS scores improved further at the 1-year follow-up . In addition , three MDMA sessions were more effective than two ( p = 0.016 )
target: There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures .
background: 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 .