Recreational Ecstasy Research Articles

Ecstasy, Marijuana and Alcohol Use by Undergraduate Students

Ecstasy is the common name for MDMA, a synthetic drug that causes changes in mood and awareness. It has been tentatively classified into a novel pharmacological class termed “entactogens” because it has a characteristic psychoactive profile that distinguishes it from classic hallucinogens and stimulants. Ecstasy is a unique modified amphetamine, with an effect profile that overlaps with those of both stimulants and hallucinogens. People take the drug in combination with other substances frequently including marijuana and alcohol. This study was aimed to investigate the relationship of the use of ecstasy, marijuana with the use of alcohol in undergraduate students from the city of São Paulo, Brazil covering samples from the north, south, east, west and center regions. The study sample comprised 907 undergraduate students. Data on lifetime and recent frequency and intensity of use for alcohol, cannabis and ecstasy was collected.METHODOLOGYThe instrument used for data collection was Google Forms TM. The instant addition of responses to the data set makes this medium appealing for research purposes. Additionally, the respondents involved in the study has been regularly using Google FormsTM, and it was therefore considered the most appropriate method for data collection. The results of the survey was statistically analyzed. Within the various areas the group of students from medical, biology, nursing, engineering, architecture, psychology, and other undergraduate areas, were chosen because their experience using these tools.RESULTSData obtained showed that in a sample of 907 students, 70 students used ecstasy, of which only 4 don't use marijuana, and also only 4 don't drink alcohol. About frequency, for ecstasy, 44% at least once, 5% weekly, 2,8% twice a week. About marijuana, in ecstasy users, the frequency was once a semester 28,57%; once in life 24,28%; everyday 14,28%; once a week 12.8%; 2 or 3 times a week 11.1% and 4 or 5 times a week 2.8%. Concerned to alcohol, in ecstasy users; 25,7% less than once a week; 24.2% twice a week; 20% once a week; 11% 3 times a week; 10% 4 times a week and 2,85% everyday.CONCLUSIONSSuddenly, silently, ecstasy is back. These findings are alarming for two further reasons: first, because ecstasy usage had previously been falling since its mid‐2000s peak; and second, are present inside university group students if consider that recent researches hypothesized that the long‐term effects of recreational ecstasy might include sleep disturbances, and changes in cognitive processing in general, and learning and memory, in particular. This work was conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration. CAAE(Br)67881517.1.0000.5511. All participants had full understanding and signed informed consent documentThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Computing the structure of language for neuropsychiatric evaluation

We describe recent preliminary studies demonstrating that computational analysis of spoken and written language can provide for highly accurate diagnostics over a wide variety of psychiatric and neurologic conditions, including psychosis, drug abuse, Parkinson's, and Alzheimer's. These results are based on the mathematical formalization of psychiatric qualitative knowledge related to the characterization of the conditions (e.g., “derailment” in psychosis) and drug effects (e.g., increased intimacy/affection with the use of the recreational drug ecstasy), as well as novel linguistic feature extraction approaches. Moreover, we show novel results using publicly available text sources suggesting that 1) it is possible to define an embedding space that allows modeling of the vast language dimension into a smaller space to map and compare different conditions, and 2) computational studies of a public personality (Ronald Reagan) can likely yield novel insights into normal aging and neurodegenerative disorders. Finally, we discuss the implications for mental health (and possibly, computer science) of a systematic application of this methodology, extended to include similar readily available behavioral data such as voice and video.

Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users.

Harmful Effects of Recreational Ecstasy Use on Memory Functioning

MDMA (3,4-methylenedioxymethamphetamine), often referred to as ‘ecstasy’, has been shown to selectively and persistently impair central serotonergic neurotransmission in laboratory animals. As of recent, evidence in human studies has suggested a link between recreational ecstasy use and a disruption of the brain’s serotonergic system. However, human neurocognitive and neuroimaging studies have yielded inconsistent findings regarding the functional impact of these neuro-adaptations, possibly due to methodological difficulties. Although the literature on the effects of recreational ecstasy use on neurocognitive function remains inconclusive, studies have most consistently shown negative effects on memory. Here, we provide a review of accumulating evidence supporting a link between recreational ecstasy use and impaired memory.

Ecstasy cannot be assumed to be 3,4‐methylenedioxyamphetamine (MDMA)

LINKED ARTICLESThis is a rebuttal by the authors (Green et al., pp. 1523–1536 of this issue) to a commentary by Parrott, pp. 1518–1520 of this issue. To view the article by Green et al. visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01819.x. To view the commentary by Parrott visit http://dx.doi.org/10.1111/j.1476‐5381.2012.01941.x

S.07.02 In vivo measurements of brain serotonergic markers and analysis of drug use profiles among recreational ecstasy and hallucinogen users

S.07. Young Scientists Award symposium 2 S.07. Young Scientists Award symposium 2 S.07.01 Frontal cortex serotonin transporter binding is positively associated with the cortisol awakening response in healthy volunteers V.G. Frokjaer 1 ° , D. Erritzoe 1 , P. Jensen 1 , P.M. Rasmussen 2 , K.K. Holst 3 , J. Madsen 4 , W. Baar´e 5 , C. Svarer 1 , G.M. Knudsen 1 . 1 Center for integrated molecular brain imaging and Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark; 2 The Danish National Research Foundation’s Center for Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark; 3 Department of Biostatistics, Copenhagen University Hospital, Copenhagen, Denmark; 4 PET and Cyclotron Unit, Copenhagen University Hospital, Copenhagen, Denmark; 5 Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark Stress vulnerability is linked to the serotonin transporter gene. Both stress and dysfunctional serotonergic neurotransmission are critical in the development and treatment of neuropsychiatric disorders. We studied associations between serotonergic markers and hypothalamic–pituitary–adrenal (HPA) axis activity in 32 healthy volunteers. Our results suggest that in mentally healthy individuals prefrontal serotonin transporter (SERT) binding is associated with basal HPA-axis reactivity. Thirty-two healthy vol- unteers (mean age 35 ±20, 7 women) underwent SERT imaging with 11C[DASB]-PET and performed saliva home-sampling of the cortisol awakening response. The cortisol awakening response (area under curve with respect to increase from baseline, AUCi) correlated positively with prefrontal SERT in a model adjusting for age and genotype (p = 0.01). The correlation was not accounted for by age, gender, BMI, personality, SERT promoter genotype, perceived stress, or seasonality (daylight minutes at scan). No significant correlation was demonstrated in midbrain (p = 0.48), pallidostriatum (p = 0.17), or occipital cortex (p = 0.88). However, a trend was observed in anterior cingulate (p = 0.07). Individuals carrying the s- or L G “stress-vulnerable” alleles of the SERT promoter gene did not show a stronger coupling between frontal SERT binding and the cortisol awakening response as tested by an interaction analysis. Our results are consistent with the hypothesis that prefrontal serotonergic neurotransmission is coupled with basal stress reactivity in healthy individuals. This coupling might be established through early neurodevelopment and seems not to be modified by SERT promoter genotype in the adult brain of mentally healthy individuals. S195 S.07.02 In vivo measurements of brain serotonergic markers and analysis of drug use profiles among recreational ecstasy and hallucinogen users D. Erritzoe 1 ° , V.F. Frokjaer 2 , C.L. Licht 2 , M. Christoffersen 2 , W. Baare 3 , T.Z. Ramshoy 3 , C. Svarer 2 , T.L. Jernigan 4 , 1 CIMBI Copenhagen and Imperial G.M. Knudsen 2 . College London, Neurobiology Research Unit in Copenhagen and Neuropsychopharmacology Unit in London, London, United Kingdom; 2 CIMBI Copenhagen and University Hospital Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark; 3 CIMBI Copenhagen and Hvidovre University Hospital, Danish Center for Magnetic Resonance Imaging, Copenhagen, Denmark; 4 CIMBI Copenhagen Hvidovre University Hospital and University of California San Diego, Danish Center for Magnetic Resonance Imaging in Copenhagen and Dept of Psychiatry in San Diego, San Diego, USA The aim of the current study was (1) to compare substance user profiles for MDMA (3,4-methylenedioxy-N-methamphetamine − ecstasy) preferring (MPU) and hallucinogen preferring users (HPU), and (2) in subgroup of these users to separate presynaptic (MDMA) from postsynaptic (MDMA and hallucinogens) drug ef- fect on in-vivo serotonergic markers using PET (positron emission tomography) [1]. Ninety-eight young recreational Danish drug users (26±5 y.o., 85 males) reporting minimum 15 illicit drug experiences and use of MDMA/hallucinogens within the last year were included and divided in MPUs (n = 50) and HPUs (n = 48) based on the relative number of lifetime exposures. A subgroup of 14 MPUs and 10 HPUs and a group of 21 non-using control subjects underwent [F-18]altanserin-(5-HT 2A )- and [11-C]DASB-(SERT)-PET. Compared to HPUs, more MPUs reported drug use at parties, in binges, administration of MDMA as tablets rather than powder, and co-use of stimulants. When compared to non-users, significant decreases in SERT binding were seen in MPUs (neocortex: −59%, pallidostriatum: −19%) but not in HPUs. The SERT binding was negatively correlated to the number of lifetime MDMA exposures, and the time of abstinence from MDMA was positively correlated to subcortical but not to cortical SERT binding. A small decrease in neocortical 5-HT 2A binding in the total drug user group was also detected. Since MDMA but not hallucinogen use was found to be asso- ciated with decreases in cerebral SERT binding, our data suggest that this effect is mediated through a direct presynaptic MDMA effect rather than by the 5-HT 2A agonistic effects of MDMA.

Event related potential (ERP) evidence for selective impairment of verbal recollection in abstinent recreational methylenedioxymethamphetamine (“Ecstasy”)/polydrug users

Ecstasy is a recreational drug whose active ingredient, 3,4-methylenedioxymethamphetamine (MDMA), acts predominantly on the serotonergic system. Although MDMA is known to be neurotoxic in animals, the long-term effects of recreational Ecstasy use in humans remain controversial but one commonly reported consequence is mild cognitive impairment particularly affecting verbal episodic memory. Although event-related potentials (ERPs) have made significant contributions to our understanding of human memory processes, until now they have not been applied to study the long-term effects of Ecstasy. The aim of this study was to examine the effects of past Ecstasy use on recognition memory for both verbal and non-verbal stimuli using ERPs. We compared the ERPs of 15 Ecstasy/polydrug users with those of 14 cannabis users and 13 non-illicit drug users as controls. Despite equivalent memory performance, Ecstasy/polydrug users showed an attenuated late positivity over left parietal scalp sites, a component associated with the specific memory process of recollection. [corrected] This effect was only found in the word recognition task which is consistent with evidence that left hemisphere cognitive functions are disproportionately affected by Ecstasy, probably because the serotonergic system is laterally asymmetrical. Experimentally, decreasing central serotonergic activity through acute tryptophan depletion also selectively impairs recollection, and this too suggests the importance of the serotonergic system. Overall, our results suggest that Ecstasy users, who also use a wide range of other drugs, show a durable abnormality in a specific ERP component thought to be associated with recollection.

P.3.017 In vivo measurements of brain serotonergic markers and analysis of drug use profiles among recreational ecstasy and hallucinogen users

Hydrolysis of p-nitrophenyl acetate catalyzed by cyclodextrin (CD) covalently bound to poly(vinylamine) was carried out. The mechanism of the catalytic process was compared with that of the analog mixture of nonbonded CD and poly(vinylamine). The covalently bonded catalyst exhibits a Michaelis-Menten type kinetics involving an intermediate complex as βCD alone does. NH2 functions of the polymer act cooperatively with CD residues by a nucleophilic attack of the included substrate. Experiments carried out with polymers of variable degree of substitution by CD showed that the best catalytic power is observed for the systems having the largest excess of amino groups.

MDMA: Neurohormonal, Neurocognitive, and Psychobiological Aspects of Recreational Ecstasy

This Ecstasy/MDMA symposium was held at the Annual Conference of the Australian Psychological Society, Hobart, Tasmania, in September 2008. The Australian government has been funding research into MDMA for many years, and hence there are several Australian groups at the forefront of international research in this field. Included in the studies reported here, were collaborations with universities from other countries. The main focus was on human studies, although animal psychopharmacology findings were also presented. The topics covered within this half-day symposium included Ecstasy dependence, the problems reported by recreational users, the influence of other psychoactive drugs, the Internet as a research tool, the contributory role of neurohormones such as oxytocin and cortisol, and the energetic stress model for recreational Ecstasy/MDMA.

The harmful health effects of recreational ecstasy: a systematic review of observational evidence

The harmful health effects of recreational ecstasy: a systematic review of observational evidence

Dance Clubbing on MDMA and during Abstinence from Ecstasy/MDMA: Prospective Neuroendocrine and Psychobiological Changes

Background/Aims: The present study is the first to prospectively compare a group of recreational Ecstasy users when dance clubbing on 3,4-methylenedioxymethamphetamine (MDMA) and when clubbing during abstinence from Ecstasy/MDMA. Methods: Twelve normal healthy volunteers (mean age = 23.2 years) were assessed at a Saturday night dance club under self-administered MDMA. On the other weekend they went to the same dance club without taking MDMA (order counterbalanced). Both conditions involved 5 test sessions conducted at similar times: pre-drug baseline, 1 h post-drug clubbing, 2.5 h post-drug clubbing, and 2 and 4 days later. The assessments included body and ambient temperature, physical activity (pedometer), as well as self-ratings for mood state, physical activity, thermal comfort and thirst. Saliva samples were analyzed for MDMA, cortisol and testosterone. Results: The cortisol levels increased significantly by 800% when dance clubbing on MDMA, while testosterone increased significantly by 75%; neither neuroendocrine measure was altered during abstinence. Saliva analyses confirmed the presence of MDMA when dancing on Ecstasy and its absence when dancing off Ecstasy. The pedometer values and self-rated levels of dancing were similar at both weekends. Hot and cold flushes and feeling hot increased significantly under MDMA. The mean body temperature did not change significantly, although there was a borderline trend for increased values after MDMA. Feelings of happiness and excitement increased under MDMA, although they were not significantly greater than when clubbing during abstinence. Conclusions: Neurohormonal release may be an important part of the acute MDMA experience. The large cortisol increase provides further data on the bioenergetic stress model of recreational Ecstasy/MDMA.

Picture Quiz: A Case of Acute Hepatitis

A 19 year old male with no previous medical history presented to hospital with an eight day history of jaundice and general malaise. He was homosexual with a history of unprotected sex with multiple partners over the last two years. He drank heavily in binge sessions and occasionally recreational drug use, cocaine and ecstasy but he had never injected. There was no history of recent travel. He had never had a previous HIV test or Sexual Transmitted Infection screen.

Minimal, Recreational Ecstasy Use Linked to Cognitive Deficits

Minimal, Recreational Ecstasy Use Linked to Cognitive Deficits

Is Recreational Ecstasy (MDMA) Use Associated with Higher Levels of Depressive Symptoms?

Due to potential serotonergic deficits, 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) may cause long-term mood disruptions in recreational Ecstasy users. The purpose of this review is to evaluate the evidence for a relationship between recreational Ecstasy use and higher levels of depressive symptoms. Eleven out of 22 studies initially have reported significantly higher depression scores in Ecstasy users in comparison to control participants. However, only three studies ultimately have revealed significantly higher depression scores in comparison to cannabis or polydrug controls. Furthermore, most studies have suffered from methodological weaknesses, and the levels of depressive symptoms that have been found in Ecstasy users have not been shown to be much higher than those found in normative groups. The evidence for an association specifically between Ecstasy use and higher levels of depressive symptoms is currently unconvincing, but the frequent concomitant use of Ecstasy and other illicit drugs has been shown to be associated with higher levels of depressive symptoms. Possible causes include polydrug use in general, MDMA-induced serotonergic deficits, individual effects of illicit drugs besides Ecstasy, combined effects of MDMA and other illicit drugs, and preexisting differences in the levels of depressive symptoms in Ecstasy users.

Problematic versus non-problematic ecstasy/MDMA use: the influence of drug usage patterns and pre-existing psychiatric factors

Recreational ecstasy (3,4-methylenedioxymethamphetamine; MDMA) use has been increasingly associated with a number of psychiatric symptoms and psychological problems. However, previous studies assessing possible psychopathological effects have not identified whether users consider their ecstasy use "problematic" or not. In addition, research has generally failed to address the potential role of premorbid psychiatric status. This study aimed to assess whether premorbid psychiatric history and/or patterns of ecstasy use would be associated with the degree of self-reported problems attributable to ecstasy. Problematic ecstasy users (n = 53) who had reported problems attributable to their ecstasy use were compared with non-problematic ecstasy users (n = 62), polydrug controls (n = 62) and illegal drug-naive controls (n = 111) on a recreational drug use questionnaire; a questionnaire, which ascertained personal and family psychiatric histories, and the Brief Symptom Inventory (BSI). Problematic ecstasy users exhibited significantly higher scores on a number of dimensions of the BSI compared to illegal drug-naive and/or polydrug controls. Problematic ecstasy users also exhibited significantly elevated scores on somatization, depression, anxiety and negative psychobiology compared to non-problematic ecstasy users. BSI scores for the non-problematic ecstasy users did not differ from polydrug or illegal drug-naive controls. Problematic ecstasy users reported significantly higher levels of ecstasy use, including lifetime consumption, average dosage and binge consumption compared to non-problematic ecstasy users. Additionally, a greater number of problematic ecstasy users reported personal and family psychiatric histories compared to controls and non-problematic ecstasy users. This study demonstrates two distinct ecstasy using groups: non-problematic ecstasy users who are not showing signs of psychopathology and problematic ecstasy users who are showing evidence of a range of symptoms. This data therefore partially supports the link between ecstasy dosage and negative psychological sequelae, but highlights the importance of the need to consider ecstasy-related attributions, pre-existing mental health status and vulnerability.

The sub-acute effects of recreational ecstasy (MDMA) use: a controlled study in humans

All previous studies of the sub-acute effects of ecstasy have failed to adequately control for group differences in psychopathology and past and concurrent substance use. The present study was designed to avoid these limitations. At an initial pre-drug baseline, a sample of 38 regular ecstasy users provided full substance histories and completed measures of personality and self-reported psychopathology. We then collected daily subjective measures of mood, cognitive impairment, restless sleep, sexual desire, craving for ecstasy and concomitant use of other substances for the next 9 days. The 20 participants who subsequently opted to take ecstasy during the 9-day assessment period reported modest sub-acute effects of ecstasy on negative mood and subjective cognitive impairment compared to those who did not after controlling for baseline group differences in psychopathology and frequency of ecstasy use. There were no significant sub-acute effects of ecstasy on interest in sexual activity or craving for ecstasy. After further controlling for co-use of alcohol with ecstasy, and the sub-acute effects of ecstasy on sleep, the sub-acute effect on mood remained marginally statistically significant but the subacute effect on cognitive impairment did not. The present findings suggest that the sub-acute effects of ecstasy in regular recreational users are relatively modest and transient but that such genuine effects may have been masked by, perhaps more clinically significant, chronic sequelae of regular ecstasy use in all previous studies of recreational ecstasy users.

A Clinical Crossroads for MDMA

Clinical studies of MDMA have been hindered by the fear of harming participants through MDMA-induced neurotoxicity. However, experimental animal studies and brain imaging studies of recreational Ecstasy users have not evidenced that a therapeutic dose of MDMA would be sufficient to cause long-term serotonergic deficits. Furthermore, the issue of potential neurotoxicity may not be as important as it first seems since certain chemicals have been shown to protect against MDMA-induced neurotoxicity. Although clinical studies conducted thus far have been promising, more research into the effects of MDMA administration in humans is needed before solid conclusions can be made in respect to the possibility of safely using MDMA as an adjunct to therapy. Finally, a clear distinction should be maintained between the recreational and clinical use of MDMA.

Impulsivity, inhibition and negative priming in ecstasy users

A modified Stroop color-word interference paradigm was used to investigate the effects of recreational ecstasy (MDMA) use on central executive inhibitory processes. Ecstasy users who also used cannabis were compared with non-users matched for cannabis consumption and with non-drug users on a Stroop task in which standard color-word interference trials were interspersed with trials in which the target color was the same as the distractor word on the immediately preceding trial. Ecstasy's effects on standard inhibition (conscious suppression of a prepotent response pattern—responsible for Stroop interference) could thus be contrasted with its effect on the short-term, unconscious, inhibitory process responsible for suppression of the preceding distractor word (negative priming). Neither drug group differed from the non-drug users in level of Stroop interference but ecstasy users showed reduced negative priming compared to the cannabis users and non-drug users. The loss of inhibition in the ecstasy users was not related to impulsivity assessed by two standard scales since these were similar in both drug-user groups and raised relative to the non-drug users. It is argued that previous failures to demonstrate loss of inhibition could be partly due to the fact that standard executive function tests, such as the Stroop, are unable to differentiate between sub-types of inhibition, only some of which may be affected by ecstasy use.

Mood and impulsivity of recreational Ecstasy users in the week following a “rave”

Two days following widely attended “rave” or dance party events, questionnaires assessing mood (Beck Depression Inventory, or BDI-II) and impulsivity (Impulsiveness, Venturesomeness and Empathy Scale, or IVE) were completed by 43 attendees who reported using Ecstasy at the events, and by 31 Ecstasy-naïve controls who attended the same events. Participants who had taken Ecstasy at the events were significantly more depressed two days later than controls, according to analysis of their BDI-II scores. There was no group difference in impulsivity as measured by the IVE. Levels of self-reported Ecstasy use were not related to depression or impulsivity scores. Results are considered in terms of the hypothetical mood effect of short-term depletion of serotonin induced by MDMA, as well as several alternative non-pharmacological explanations.

Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy

This review of chronic tolerance to MDMA (3,4-methylenedioxymetamphetamine) covers the empirical data on dosage escalation, reduced subjective efficacy and bingeing in recreational Ecstasy users. Novice users generally take a single Ecstasy tablet, regular users typically take 2-3 tablets, whereas the most experienced users may take 10-25 tablets in a single session. Reduced subjective efficacy following repeated usage is typically described, with many users subjectively reporting the development of tolerance. Intensive self-administration or bingeing is often noted by experienced users. This can comprise 'stacking' on several tablets together, and 'boosting' on successive doses over an extended period. Some experienced users snort Ecstasy powder nasally, whereas a small minority inject MDMA. Chronic tolerance and bingeing are statistically linked to higher rates of drug-related psychobiological problems. In terms of underlying mechanisms, neuroadaptive processes are certainly involved, but there is a paucity of evidence on hepatic and behavioural mechanisms. Further studies specifically designed to investigate chronic tolerance, involving low intermittent dose regimens, are required. Most animal research has involved intensive MDMA dosing regimens designed to engender serotonergic neurotoxicity, and this may comprise another underlying mechanism. If distal serotonin axon terminal loss was also developing in recreational users, it may help to explain why reducing subjective efficacy, dosage escalation and increasing psychobiological problems often develop in parallel. In conclusion, there is extensive evidence for chronic pharmacodynamic tolerance to recreational Ecstasy/MDMA, but the underlying mechanisms are currently unclear. Several traditional processes are probably involved, but one of the possible causes is a novel mechanism largely unique to the ring substituted amphetamine derivatives, namely serotonergic neurotoxicity.