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Zusammenfassung Hintergrund Für die Behandlung von Menschen mit Schizophrenien wird vorrangig antipsychotische Monotherapie empfohlen. Antipsychotische Polypharmazie (APP) wird dennoch oft eingesetzt und dient als Qualitätsindikator. Ziel der Arbeit Das Auftreten von APP an 9 psychiatrischen Kliniken des LVR zu untersuchen und die Nutzbarkeit als Qualitätsindikator zu diskutieren. Material und Methoden Es wurden Behandlungsdaten von stationären und teilstationären Fällen mit der Hauptdiagnose ICD-10 F20.x im Zeitraum 6/2016 bis 6/2017 hinsichtlich der APP-Rate analysiert. Ergebnisse Bei 6788 Behandlungsfällen wurde eine APP-Rate von 55,5 % ermittelt. Männliches Geschlecht, längere Verweildauer, keine Zwangsunterbringung und der Standort der Klinik waren mit APP assoziiert. Diskussion Die APP-Rate ist im Vergleich bisherigen Ergebnissen hoch und weist erhebliche Unterschiede zwischen den Kliniken auf. Die Verwendung des Qualitätsindikators APP wird diskutiert.

Background Amphetamine-type stimulants (ATS) have become a critical public health issue. Animal models have indicated a clear neurotoxic potential of ATSs. In humans, chronic use has been associated with cognitive deficits and structural brain abnormalities. However, cross-sectional retrospective designs in chronic users cannot truly determine the causal direction of the effects. Objective To prospectively determine effects of occasional ATS use on cognitive functioning and brain structure. Methods In a prospective longitudinal study design, cognitive functioning and brain structure were assessed at baseline and at 12-month follow-up in occasional ATS users (cumulative lifetime use Results Examination of change scores between the initial examination and follow-up revealed declined verbal memory performance and putamen volume in users with high relative to low interim ATS exposure. In the entire sample, interim ATS use, memory decline, and putamen volume reductions were strongly associated. Conclusions The present findings support the hypothesis that ATS use is associated with deficient dorsal striatal morphology that might reflect alterations in dopaminergic pathways. More importantly, these findings strongly suggest that even occasional, low-dose ATS use disrupts striatal integrity and cognitive functioning.

Background The purpose of this study was to identify factors associated with a high risk of involuntary psychiatric in-patient hospitalization both on the individual level and on the level of mental health services and the socioeconomic environment that patients live in. Methods The present study expands on a previous analysis of the health records of 5764 cases admitted as in-patients in the four psychiatric hospitals of the Metropolitan City of Cologne, Germany, in the year 2011 (1773 cases treated under the Mental Health Act and 3991 cases treated voluntarily). Our previous analysis had included medical, sociodemographic and socioeconomic data of every case and used a machine learning-based prediction model employing chi-squared automatic interaction detection (CHAID). Our current analysis attempts to improve the previous one through (1) optimizing the machine learning procedures (use of a different type of decision-tree prediction model (Classification and Regression Trees (CART) and application of hyperparameter tuning (HT)), and (2) the addition of patients’ environmental socioeconomic data (ESED) to the data set. Results Compared to our previous analysis, model fit was improved. Main diagnoses of an organic mental or a psychotic disorder (ICD-10 groups F0 and F2), suicidal behavior upon admission, admission outside of regular service hours and absence of outpatient treatment prior to admission were confirmed as powerful predictors of detention. Particularly high risks were shown for (1) patients with an organic mental disorder, specifically if they were retired, admitted outside of regular service hours and lived in assisted housing, (2) patients with suicidal tendencies upon admission who did not suffer from an affective disorder, specifically if it was unclear whether there had been previous suicide attempts, or if the affected person lived in areas with high unemployment rates, and (3) patients with psychosis, specifically those who lived in densely built areas with a large proportion of small or one-person households. Conclusions Certain psychiatric diagnoses and suicidal tendencies are major risk factors for involuntary psychiatric hospitalization. In addition, service-related and environmental socioeconomic factors contribute to the risk for detention. Identifying modifiable risk factors and particularly vulnerable risk groups should help to develop suitable preventive measures.

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 prospectively assess brain structural markers for escalating drug use in two independent samples 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 samples 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 samples 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.

Background Methamphetamine is considered more dangerous than other stimulants because of its acute complications, long-term neurotoxicity, and potential for drug dependence. Until now, there have been no evidence-based guidelines for the treatment of methamphetamine-related disorders, either in Germany or abroad. Methods A systematic literature search was performed on the treatment of methamphetamine-related disorders. Based on this literature review, a multidisciplinary expert panel developed recommendations using the nominal group technique. Results The evidence base for the treatment of methamphetamine-related disorders is sparse. The efficacy of psychotherapeutic techniques such as cognitive behavioral therapy and contingency management and the efficacy of complex, disorder-specific treatment programs have been proven in ran - domized controlled trials, but it remains unclear which method is best. Persons carrying a diagnosis of substance abuse should be offered psychotherapy. Structured exercise programs, whether self-directed or professionally led, can improve addiction-specific endpoints as well as comorbid disorders and should, therefore, be offered as well. Pharmacotherapy has shown little to no effect in relatively low-quality clinical trials with low case numbers and high dropout rates, and therefore only a few weak recommendations were made. These include tranquilizers for the short-term treatment of agitation and atypical antipsychotics if necessary. Attempts to substitute other substances, such as methylphenidate or dexamphetamine, for methamphetamine have not yielded any robust evidence to date. Sertraline should not be administered due to serious adverse events. Conclusion Many of the recommendations in the guideline are made with a weak grade of recommendation because of the poor evidence base and the modest size of the reported therapeutic effects. In acute situations, symptomoriented treatment is recommended. Psychotherapy and exercise should be offered as well.

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 methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological 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 cannot completely ascribed to the use of MDMA.

Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies.

Passivity experiences are hallmark symptoms of schizophrenia that can be characterized by the belief that one's thoughts or actions are controlled by an external agent. It has recently been suggested that these psychotic experiences result from defective monitoring of one's own actions, i.e. disturbed comparison of actions and perceived outcomes. In this study, we examined the function of the previously characterized action monitoring network of the inferior parietal lobule (IPL), medial (mPFC) and lateral prefrontal cortices in patients with different levels of passivity symptoms with an fMRI task. The visuomotor fMRI task demanded control of visually perceived object movements by alternating button presses with the left and the right index finger. In the monitoring condition of this task subjects stopped their actions whenever they detected visuomotor incongruence. fMRI and behavioural data from 15 patients were tested for correlation with passivity symptoms using standardized Scale for Assessment of Positive Symptoms (SAPS)- and AMDP- passivity symptom ratings. Both types of data were tested for differences between the patients group and 15 healthy controls. In the patient group we found the expected correlation of passivity symptoms and visuomotor monitoring performance. There was a significant positive correlation of passivity symptoms with increased latency of incongruence detection and a negative correlation of SAPS-passivity with the number of detected events. fMRI data revealed correlations of passivity symptoms with activation in bilateral IPL, primary motor and sensory cortices in the action monitoring condition. A correlation of passivity symptoms with the main experimental effect (actions with -- actions without monitoring) was found in the posterior cingulate cortex (PCC) and in the left IPL. No group differences or group by task interactions were found within the visuomotor-action-monitoring network. Our results demonstrate the association between passivity symptoms and the dysfunction of visuomotor action monitoring and support the idea that psychotic passivity experiences result from dysfunctions of central action monitoring mechanisms: According to pre-existing concepts of parietal cortex function, IPL-hyperactivation may represent an increase in false detections of visuomotor incongruence while the correlation between passivity and the differential effect of monitoring on PCC-activation assumedly represents greater self-monitoring effort in passivity experiences.

Rationale Many studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-d-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model). Objectives The aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design. Materials and methods Fifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation. Results Nine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN. Conclusions The NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.

Patients with schizophrenic psychosis and a comorbid addiction disorder account for about 50% (lifetime prevalence) and 25–30% (6-month prevalence) of all patients with psychosis (1– 3). These cases are referred to as dual diagnosis patients. Often, young men of a low educational status are affected and the disease course tends to be unfavorable with a poor prognosis (2– 5): dual diagnosis patients experience psychotic relapses and emergency admissions more frequently, and their disorder is more prone to becoming chronic. Such patients often display aggressive behaviors directed towards themselves and others, and they have poorer sociorehabilitative results in the long term than other patients with psychosis (3, 5). Primarily because of their relatively poor compliance, dual diagnosis patients are regarded as difficult to treat. They often encounter therapeutic nihilism from health professionals (6). On the basis of model projects and controlled studies, integrated therapeutic programs have been favored since the 1990s, in which the treatment is administered in an integrative setting and by a team that has experience and competence in treating both disorders (2, 3, 7– 9). Measures that have been described as successful in the long term are motivational, low-threshold programs that were conceived for a longer period and include psychoeducational, behavioral therapeutic, and occasionally family therapy elements. Although the 2006 S3 guideline for schizophrenia recommended implementing these programs in standard care (10), progress since then has been slow. Recent randomized studies and meta-analyses have taken a more critical view of the effectiveness of integrated treatment programs: success seems low and only partial, so that the cost–benefit ratio is regarded with some skepticism (11– 15). In spite of indications of the clinical relevance of even small effects that may be stronger in subgroups, no indicators of the preconditions for the observed therapeutic responses have been identified thus far. Accordingly, the 2011 guideline from the UK National Institute for Health and Care Excellence (NICE, National Institute for Health and Clinical Excellence at the time) recommends offering therapeutic measures for both disorders but does not recommend any particular program and neither does it demand an integrated approach (16). Most randomized studies are from the US or European countries, whose healthcare systems differ from Germany’s. From Germany, only one randomized study has been reported that evaluated a brief inpatient motivational intervention (MI) and showed that, subsequent to inpatient treatment, the MI group used the outpatient therapeutic services to a greater degree than controls. No benefits were observed regarding substance use (17). The present study evaluated a long-term, trans-sector, integrated treatment program for dual diagnosis patients with a follow-up period of 12 months under standard treatment conditions.

Neurotoxic damage of central serotonergic systems has been demonstrated in numerous animal studies after exposure to methylenedioxyamphetamines (ecstasy). A high intensity dependence of auditory evoked potentials and, particularly, of the tangential N1/P2 source activity has been associated with low levels of serotonergic neurotransmission in humans. We performed an auditory evoked potentials study in 28 abstinent recreational ecstasy users and two equally sized groups of cannabis users and nonusers. The ecstasy users exhibited an increase of the amplitude of the tangential N1/P2 source activity with higher stimulus intensities; whereas, both control groups failed to exhibit this feature. These data are in line with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity. This feature of information processing is probably related to the well-recognized neurotoxic potential of ecstasy. Our data indicate that recreational ecstasy use may cause long-term alterations in the function (and possibly structure) of the human brain.

Objective: Cannabis use is widespread among patients with schizophrenia despite its negative impact on the course of the disease. Craving is a considerable predictor for relapse in people with substance use disorders. Our investigation aimed to gain insight into the intensity and dimensions of cravings in patients with schizophrenia and cannabis use disorders (CUDs), compared with otherwise healthy people with CUDs (control subjects). Method: We examined 51 patients with schizophrenia and CUDs and 51 control subjects by means of the Cannabis-Craving Screening questionnaire. Results: We found greater overall intensity of craving and greater relief craving in patients with schizophrenia and CUDs. Reward craving was greater in the CUDs group. Relief craving was associated with symptoms of schizophrenia in patients with schizophrenia and CUDs. Conclusion: Our findings are in line with the view that aspects of self-medication or affect regulation may account (at least in part) for cannabis use in people with schizophrenia. A better understanding of the dimensions of craving may help to improve targeted therapeutic interventions that aim to reduce drug consumption in this difficult-to-treat patient group.

Qualitative poor decision-making and associated altered neuronal activation patterns have been described for the users of several drugs, amongst others for stimulants like amphetamine and MDMA. Deficits in decision-making might be caused by an augmented attraction to short-term rewarding properties despite negative long-term consequences, leading to rigid stimulus–response patterns. In the present imaging study, we investigated decision-making and associated neuronal activation in three groups differing in their exposure to amphetamine and MDMA. An established paradigm on risky choices was used to evaluate decision-making performance and corresponding functional magnet resonance imaging (fMRI) activation. Subjects could choose between a low-risk control gamble and an experimental gamble, which always differed in the probability of winning or losing, as well as the magnitudes of monetary gain or loss. Experienced users (EU), users with low exposure to stimulants and drug-naive controls, did not differ from each other in behavioral performance. In accordance with our hypotheses, the anticipation of reward led to an activation of primarily the frontal cortex and the striatum in low-exposure users and drug-naive controls. In contrast, frontal and parietal activation was observed in all groups when the actual outcome of an experimental gamble was presented. EU displayed more activation compared to both control groups when there was a high probability of winning. The study at hand supports the hypothesis that neuronal activation patterns might even differ between drug users and healthy controls when no behavioral deficits are apparent. In EU, the probability of the occurrence of an event has more influence on neuronal activation than on the actual magnitude of reinforcing properties of this event.

Amphetamine-type stimulants (ATS) refer to a group of drugs whose principal members include amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Worldwide, ATS are among the most common illicit drugs. Therefore, understanding whether and to what extent ATS exposure affects brain structure and functioning in recreational users has become a critical public health issue. We studied gray and white matter densities in 20 experienced users of ATS (more than 100 units MDMA and/or 50 g of amphetamine lifetime dose), 42 low exposure users with very limited ATS experience (less than 5 units lifetime dose) and 16 drug-naive controls. A tract-based spatial statistics (TBSS) analysis of fractional anisotropy images was applied to diffusion magnetic resonance imaging (MRI) data. Furthermore, alignment invariant white matter tract representations acquired from the TBSS analysis were used as a reference for inter-subject brain registrations in a voxel-based morphometry (VBM) analysis of gray matter volume, reducing characteristic alignment inaccuracies associated with this voxel-wise gray matter investigation approach. Between-group white matter comparison revealed no significant results. However, compared to low exposure users, experienced users showed several regions of lower gray matter volume in medial frontal regions, in particular the orbital and medial frontal cortex. Differences are likely to reflect effects of repeated ATS exposure even in recreational users. However, differences in pre-existing or confounding factors might also account for between-group differences.

Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies.

Introduction Substance use disorders are highly prevalent among people with schizophrenia. Dually diagnosed patients present with unfavorable course and poor long-term outcomes. Integrated, motivation-based treatment for both disorders in the same setting is considered the treatment of choice. However, integrated treatment programs are not readily available and effect sizes of the programs are modest. Objectives To evaluate an integrated psychosocial treatment program for people with schizophrenia and substance use disorders in the setting of a community psychiatric hospital. Methods 100 in-patients with schizophrenia and substance use disorders were randomized to Integrated Treatment (IT) or Treatment as usual (TAU). The IT group was initially treated in a specialized open ward; upon discharge they were offered treatment in a specialized out-patient program of the hospital. The TAU group was initially treated in another non-specialized open ward; upon discharge they were offered treatment in the non-specialized out-patient unit of the hospital. TAU included pharmacotherapy, medical treatment, supportive psychotherapy and further aids by nursing staff and social workers. IT included all elements of TAU plus manualized group therapy with motivational interviewing, psychoeducation and cognitive-behavioral approaches. Assessments were performed at baseline and after 3, 6 and 12 months. Results The IT group had slightly less drop-outs in the follow-up period (non-significant). The IT group was more satisfied with treatment and they developed a higher motivation to reduce substance use. Both groups succeeded in reducing substance use during follow-up, whereas the IT group did slightly better (non-significant).

Contemporary theories of motor control assume that motor actions underlie a supervisory control system which utilizes reafferent sensory feedbacks of actions for comparison with the original motor programs. The functional network of visuomotor action monitoring is considered to include inferior parietal, lateral and medial prefrontal cortices. To study both sustained monitoring for visuomotor incongruence and the actual detection of incongruence, we used a hybrid fMRI epoch-/event-related design. The basic experimental task was a continuous motor task, comprising a simple racing game. Within certain blocks of this task, incongruence was artificially generated by intermittent takeover of control over the car by the computer. Fifteen male subjects were instructed to monitor for incongruence between their own and the observed actions in order to abstain from their own action whenever the computer took over control. As a result of both sustained monitoring and actual detection of visuomotor incongruence, the rostral inferior parietal lobule displayed a BOLD signal increase. In contrast, the prefrontal cortex (PFC) exhibited two different activation patterns. Dorsolateral (BA 9/46) and medial/cingulate (BA 8, BA 32) areas of the PFC displayed a greater increase of activation in sustained monitoring, while ventrolateral PFC showed greater event-related activation for the actual detection of visuomotor incongruence. Our results suggest that the rostral inferior parietal lobule is specifically involved in the reafferent comparison of the test subjects’ own actions and visually perceived actions. Different activation patterns of the PFC may reflect different frontoparietal networks for sustained action monitoring and actual detection of reafferent incongruence.

Patients with schizophrenia exhibit disturbances of orienting of attention. However, findings have been inconsistent. Pharmacologic challenges with hallucinogens have been used as models for psychosis. The NMDA antagonist state (PCP, ketamine) resembles undifferentiated psychoses with positive and negative symptoms, while the 5-HT(2A) agonist state (LSD, dimethyltryptamine (DMT)) is thought to be an appropriate model for psychoses with prominent positive symptoms. The aim of this study was to investigate orienting of attention in the human NMDA antagonist and 5-HT(2A) agonist models of psychosis. A total of 15 healthy volunteers participated in a randomized, double-blind, crossover study with a low and a high dose of DMT and S-ketamine, which elicited subtle 'prepsychotic' or full-blown psychotic symptoms (low and high dose, respectively). Nine subjects completed both experimental days with the two doses of both drugs. Overall, both hallucinogens slowed down reaction times dose dependently (DMT >S-ketamine) and DMT diminished the general response facilitating (alerting) effect of spatially neutral cues. Inhibition of Return (IOR), that is, the normal reaction time disadvantage for validly cued trials with exogenous cues and long cue target intervals, was blunted after both doses of DMT and the low dose of S-ketamine. IOR reflects an automatic, inhibitory mechanism of attention, which is thought to protect the organism from redundant, distracting sensory information. In conclusion, our data suggest a deficit of IOR in both hallucinogen models of psychosis, with the effect being clearer in the serotonin model. Blunted IOR may underlie or predispose to different psychotic manifestations, but particularly to those with prominent positive symptoms.

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.

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).