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3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) has become a widely used recreational drug among young people. This is of great concern, since MDMA is neurotoxic in animal studies and its use has been associated with psychological distress and a variety of self-reported psychiatric symptoms. However, exploring the origins of psychopathology in ecstasy users is hampered by the frequent polydrug use and by the cross-sectional design of all investigations, so far.The present study combines a cross-sectional with a longitudinal approach to further clarify the impact of the use of other illicit drugs on psychopathological symptoms reported by ecstasy users.At baseline, we administered self-rating scales for impulsivity, sensation seeking and general psychological complaints to 60 recreational ecstasy users and 30 matched controls. From the initial sample of ecstasy users, 38 subjects were re-examined 18 months later. RESULTS. At baseline, ecstasy users reported significantly more psychological complaints than controls. However, self-reported psychopathology was mainly associated with regular cannabis use. At follow-up, subjects who had abstained from ecstasy use during the follow-up period did not differ from those reporting continued consumption. In contrast, subjects with regular concomitant cannabis use during the follow-up period reported more anxiety, interpersonal sensitivity and obsessive-compulsive behaviour than cannabis-abstinent users. Finally, higher levels of obsessive-compulsive behaviour, interpersonal sensitivity, depression, anxiety, phobic anxiety and paranoid ideation were significantly correlated with the duration of regular interim cannabis use.The present findings suggest that self-reported psychopathology in ecstasy users is predominantly attributable to concomitant use of cannabis. Abstinence from cannabis and not ecstasy seems to be a reliable predictor for remission of psychological complaints in ecstasy users.

Das psychoedukative Training fur Patienten mit der Doppeldiagnose Psychose und Missbrauch/Abhangigkeit (PTDD) wurde an der psychiatrischen Klinik der RWTH Aachen entwickelt und findet hier seit Anfang 2001 Anwendung. Es wird auf der Schwerpunktstation fur DD-Patienten angeboten (s. Abschnitt 5.2), steht jedoch auch teilstationaren und ambulanten Patienten der Einrichtung zur Verfugung.

Der Vorsatz ein spezialisiertes Behandlungsprogramm fur DD-Patienten zu etablieren entstand im Jahr 2000 auf einer offenen Station des Universitatsklinikums Aachen. Es handelt sich um eine relativ kleine Einheit von 14 Betten, die ursprunglich mit dem Schwerpunkt auf die Fruhrehabilitation junger, postakuter bzw. (teil-)remittierter schizophrener Patienten eroffnet worden war. Ein Teil der Patienten wird nach Besserung der akuten psychotischen Symptomatik vom geschutzten Bereich auf diese Station ubernommen, andere Patienten werden direkt elektiv nach Uberweisung von niedergelassenen Arzten z. B zur medikamentosen Umstellung und/oder sozio- und verhaltenstherapeutischen Behandlung aufgenommen. Die Aufenthaltsdauer betragt in der Regel 3–6 Wochen. In dieser Zeit wird die Pharmakotherapie optimiert und die Patienten werden auf den Wiedereinstieg in den Beruf oder weitere berufliche/soziale rehabilitative Masnahmen in tagesklinischen oder komplementaren Einrichtungen vorbereitet. Einmal wochentlich findet eine Einzelvisite statt, ansonsten werden alle Patienten taglich in einer Gruppenvisite gesehen.

Hallucinogenic drug-induced states are considered as models for acute schizophrenic disorders (experimental psychoses). In a double-blind study with healthy volunteers we investigated the influence of the serotonergic hallucinogen psilocybin, the ecstasy-like drug 3,4-methylenedioxyethylamphetamine (MDE), the stimulant d- methamphetamine and placebo on covert orienting of spatial attention (n = 8 in each group). Reaction times were prolonged after ingestion of psilocybin > MDE, but not after d-methamphetamine. In addition, subjects on psilocybin exhibited particularly slow reaction times in invalid trials at short cue target intervals and failure of response inhibition in valid trials at long cue target intervals for right visual field targets. Despite some methodological limitations, these results are in line with both bilateral impairment of disengagement of attention and a lateralized impairment of inhibition of return (IOR) in productive psychotic states. Additional investigations with larger samples, different hallucinogenic substances (serotonergic agonists vs. NMDA antagonists) and different dose regimens are needed in order to further explore the suggested relationship between visuospatial attentional dysfunction and acute psychotic conditions.

Background: The purpose of this study was to investigate neuroendocrine function in ecstasy (3,4-methylenedioxymethamphetamine = MDMA) users and controls. Methods: Prolactin response to d-fenfluramine was assessed in abstinent ecstasy users with concomitant use of cannabis only (n = 24, male/female 13/11) and in two control groups: healthy nonusers (n = 13, female) and exclusive cannabis users (n = 7, male). Results: Prolactin response to d-fenfluramine was slightly blunted in female ecstasy users. Both male user samples exhibited a weak prolactin response to d-fenfluramine, but this was weaker in the group of cannabis users. Baseline prolactin and prolactin response to d-fenfluramine were associated with the extent of previous cannabis use. Conclusions: Endocrinological abnormalities of ecstasy users may be closely related to their coincident cannabis use. Cannabis use may be an important confound in endocrinological studies of ecstasy users and should be looked for more systematically in future studies.

Objectives—Ecstasy(3,4-methylenedioxymethamphetamine (MDMA) and related congerers: MDA, MDEA) is the name given to a group of popular recreational drugs. Animal data raise concern about neurotoxic eVects of high doses of ecstasy on central serotonergic systems. The threshold dose for neurotoxicity in humans is not clear and serotonin is involved in several functions including cognition. The purpose of this study was to investigate cognitive performance in a group of typical recreational ecstasy users. Methods—A comprehensive cognitive test battery was administered to 28 abstinent ecstasy users with concomitant use of cannabis only and to two equally sized matched groups of cannabis users and non-users. The sample consisted of ecstasy users with a typical recreational use pattern and did not include very heavy users. Results—Ecstasy users were unimpaired in simple tests of attention (alertness). However, they performed worse than one or both control groups in the more complex tests of attention, in memory and learning tasks, and in tasks reflecting aspects of general intelligence. Heavier ecstasy and heavier cannabis use were associated with poorer performance in the group of ecstasy users. By contrast, the cannabis users did not diVer significantly in their performance from the non-users. Conclusions—The present data raise concern that use of ecstasy possibly in conjunction with cannabis may lead to cognitive decline in otherwise healthy young people. Although the nature of the emerging cognitive disturbance is not yet clear, an impairment of working memory might be the common denominator underlying or contributing to declines of performance in various tasks. The cognitive disturbance is likely to be related to the well recognised neurotoxic potential of ecstasy. The data suggest that even typical recreational doses of ecstasy are suYcient to cause neurotoxicity in humans. (J Neurol Neurosurg Psychiatry 2000;68:719‐725)

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

A HPLC method has been developed for the analogue of Ecstasy MDE and its major metabolites N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) and 3,4-methylenedioxyamphetamine (MDA) in human plasma. In the course of our investigations we found that the methylenedioxyamphetamines and HME exhibit fluorescence at 322 nm. Therefore the detection could be carried out with a fluorescence (FL) detector. Solid-phase extraction was used for sample preparation and yielded high recovery rates greater than 95%. The limit of quantitation for MDE and its metabolites in the extracts was between 1.5 and 8.9 ng/ml and the method standard deviations were less than 5%. This sensitive, rapid and reliable analytical method has been used successfully in the quantitation of the substances in plasma samples obtained from 14 volunteers in two clinical studies after p.o. administration of 100 to 140 mg MDE*HCI. The maximum plasma concentrations were 235-465 ng/ml (MDE), 67-673 ng/ml (HME) and 7-33 ng/ml (MDA), respectively. Pharmacokinetic parameters have been investigated using the plasma concentration curves.

Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca’s area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.

SummaryClinical evidence suggests that hallucinogenic drug-induced altered states of consciousness (ASCs) and the incipient, acute stages of endogenous psychoses share many common phenomenological features. The aim of our study was to assess hallucinogen-like phenomena in endogenous psychotic patients using standardised methods. We examined 93 endogenous psychotic patients, 50 healthy controls and a small group of drug induced psychotic patients (n= 7) with two ASC self-assessment scales (questionnaire APZ =AbnormerPsychischerZustand = Altered State of Consciousness [Dittrich et al, 1985]; and questionnaire OAV = Abbreviation of the three subscales:Oceanic Boundlessness/Angst = Dread of Ego Dissolution/Visionary Restructuralisation [Bodmer 1989]). Patients were examined shortly after remission of their last acute psychotic episode and they answered the questionnaires referring to the early phase of this episode. Differences in the questionnaire scores were significant between psychotic patients and controls. Drug induced patients had numerically higher scores than endogenous psychotic patients, however these differences were only significant for the APZ total score and the undifferentiated items of the APZ, but not for the three APZ subscale and the OAV scores. More than 50% of the endogenous psychotic patients answered 26% of the APZ-and 43% of the OAV-items with “yes”. The OAV total score and the OSE (OzeanischeSelbstentgrenzung = oceanic boundlessness) scores of both questionnaires correlated significantly with BPRS Factor 3 (thought disturbance). Our results support the hypothesis that hallucinogen-like experiences represent common phenomena during the acute stages of endogenous psychoses. Remarkably, these phenomena include subjectively pleasant experiences of the OSE dimension. In the routine clinical assessment of endogenous psychotic patients experiences of this dimension may be more easily overlooked than the negative experiences of the AIA dimension (AIA:Angst vor derIch-Auflösung = dread of ego dissolution).