Der Gebrauch illegaler Substanzen im deutschsprachigen Raum

Substanzkonsumstörungen belasten Betroffene und ihren Angehörigen und gehen mit hohen Kosten für die Gesellschaft einher. Da die Verbreitung des Konsums psychotroper Substanzen mit dem Risiko von Konsumstörungen verbunden ist, sind nationale Monitoring-Programme zum illegalen Substanzkonsum hilfreich zur Risiko- und Kostenabschätzung. Allerdings weisen Umfragemethoden – meist Selbstberichte in Telefoninterviews oder Onlinebefragungen, methodische Schwächen auf, wie Abwasseruntersuchungen auf Drogenrückstände in europäischen Städten nahelegen. In der vorliegenden Arbeit werden die Daten repräsentativer Umfragen aus Deutschland, Österreich und der Schweiz, zusammen mit den jüngsten Daten aus Abwasseruntersuchungen, besprochen. In Europa und im deutschsprachigen Raum steigen der Cannabiskonsum und die Nachfragen zur Behandlung von Cannabiskonsumstörungen an. Während in Deutschland zusätzlich der Amphetaminkonsum und assoziierte Behandlungsnachfragen zunehmen, scheint sich in der Schweiz v. a. der Kokainkonsum zu verbreiten. Auch der Konsum von 3,4-Methylendioxy-N-methylamphetamin („Ecstasy“) steigt in Deutschland und der Schweiz an, wie Abwasseruntersuchungen nahelegen. Opiate, wie Heroin, werden im deutschsprachigen Raum derzeit weniger konsumiert, obwohl spezialisierte Behandlungsnachfragen durch Altkonsumenten aus früheren Heroinwellen weiter hoch sind. Zukünftige drogenpolitische Regulierungsmodelle stehen vor der Herausforderung, zugleich den repressiven Anteil der Gesetzgebung zu vermindern, aber dennoch den problematischen Konsum in der Gesamtbevölkerung und besonders von Jugendlichen zu senken. Ein erster möglicher Schritt wäre die Entkriminalisierung des Konsums (nicht des Verkaufs), um Betroffene mit Substanzkonsumstörungen vor Repressionen und weiterer Marginalisierung zu schützen

How Realistic Are the Scientific Assumptions of the Neuroenhancement Debate? Assessing the Pharmacological Optimism and Neuroenhancement Prevalence Hypotheses

Since two decades, neuroenhancement is a major topic in neuroethics and still receives much attention in the scholarly literature as well as in public media. In contrast to high hopes at the beginning of the "Decade of the Brain" in the United States and Europe that we subsume under the "pharmacological optimism hypothesis," recent evidence from clinical neuroscience suggests that developing drugs that make healthy people smarter is even more difficult than finding new treatments for patients with mental disorders. However, cognitive enhancing drugs even for patients with impaired intellectual performance have not been successfully developed yet and new drugs that might have a disruptive impact on this field are unlikely to be developed in the near future. Additionally, we discuss theoretical, empirical, and historical evidence to assess whether cognitive enhancement of the healthy is common or even epidemic and if its application will further increase in the near future, as suggested by the "neuroenhancement prevalence hypothesis." Reports, surveys, and reviews from the 1930s until today indicate that psychopharmacological neuroenhancement is a fact but less common than often stated, particularly in the public media. Non-medical use of psychostimulants for the purpose of cognitive enhancement exists since at least 80 years and it might actually have been more common in the past than today. Therefore, we conclude that the pharmacological optimism hypothesis and neuroenhancement prevalence hypotheses have to be rejected and argue that the neuroenhancement debate should take the available evidence more into account

Psilocybin-induced deficits in automatic and controlled inhibition are attenuated by ketanserin in healthy human volunteers

The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system

Effects of the mu-opioid receptor agonist morphine on facial mimicry and emotion recognition

Facial mimicry and emotion recognition are two socio-cognitive abilities involved in adaptive socio-emotional behavior, promoting affiliation and the establishment of social bonds. The mu-opioid receptor (MOR) system plays a key role in affiliation and social bonding. However, it remains unclear whether MORs are involved in the categorization and spontaneous mimicry of emotional facial expressions. Using a randomized, placebo-controlled, double-blind, between-subjects design, we investigated in 82 healthy female volunteers the effects of the specific MOR agonist morphine on the recognition accuracy of emotional faces (happiness, anger, fear), and on their facial mimicry (measured with electromyography). Frequentist statistics did not reveal any significant effects of drug administration on facial mimicry or emotion recognition abilities. However, post hoc Bayesian analyses provided support for an effect of morphine on facial mimicry of fearful facial expressions. Specifically, compared to placebo, morphine reduced mimicry of fear, as shown by lower activity of the frontalis muscle. Bayesian analyses also provided support for the absence of a drug effect on mimicry of happy and angry facial expressions, which were assessed with the zygomaticus major and corrugator supercilii muscles, as well as on emotion recognition accuracy. These findings suggest that MOR activity is involved in automatic facial responses to fearful stimuli, but not in their identification. Overall, the current results, together with the previously reported small effects of opioid compounds, suggest a relatively marginal role of the MOR system in emotion simulation and perception. Keywords: EMG; Emotion recognition; Facial mimicry; Mu-opioid system; Social affiliation

Pattern of predictive features of continued cannabis use in patients with recent-onset psychosis and clinical high-risk for psychosis

Continued cannabis use (CCu) is an important predictor for poor long-term outcomes in psychosis and clinically high-risk patients, but no generalizable model has hitherto been tested for its ability to predict CCu in these vulnerable patient groups. In the current study, we investigated how structured clinical and cognitive assessments and structural magnetic resonance imaging (sMRI) contributed to the prediction of CCu in a group of 109 patients with recent-onset psychosis (ROP). We tested the generalizability of our predictors in 73 patients at clinical high-risk for psychosis (CHR). Here, CCu was defined as any cannabis consumption between baseline and 9-month follow-up, as assessed in structured interviews. All patients reported lifetime cannabis use at baseline. Data from clinical assessment alone correctly classified 73% (p  0.093), and their addition to the interview-based predictor via stacking did not improve prediction significantly, either in the ROP or CHR groups (ps > 0.065). Lower functioning, specific substance use patterns, urbanicity and a lack of other coping strategies contributed reliably to the prediction of CCu and might thus represent important factors for guiding preventative efforts. Our results suggest that it may be possible to identify by clinical measures those psychosis-spectrum patients at high risk for CCu, potentially allowing to improve clinical care through targeted interventions. However, our model needs further testing in larger samples including more diverse clinical populations before being transferred into clinical practice

Endocannabinoids and related lipids linked to social exclusion in individuals with chronic non-medical prescription opioid use.

Opioid-related overdose deaths are still on the rise in North America, emphasizing the need to better understand the underlying neurobiological mechanisms regarding the development of opioid use disorder (OUD). Recent evidence from preclinical and clinical studies indicate that the endocannabinoid system (ECS) may play a crucial role in stress and reward, both involved in the development and maintenance of substance use disorders. Animal models demonstrate a specific crosstalk between the ECS and the endogenous opioid system. However, translational studies in humans are scarce. Here, we investigated basal plasma levels of the endocannabinoids anandamide (AEA) and 2-arachidonoyglycerol (2-AG), and eight endocannabinoid-related lipids, including oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), as well as whole blood fatty acid amide hydrolase (FAAH) activity in chronic non-medical prescription opioid users (NMPOU; n = 21) compared to opioid-naïve healthy controls (n = 29) considering age, sex, and cannabis use as potential confounders. Additionally, the association of endocannabinoids and related lipids with the participants' response to experimentally induced social exclusion was examined. We found significantly elevated basal AEA, OEA, and PEA levels in NMPOU compared to controls, but no differences in FAAH activity, 2-AG, or other endocannabinoid-related lipids. Within NMPOU, higher AEA levels were associated with lower perception of social exclusion. Robust positive correlations within N-acylethanolamines (i.e., AEA, OEA, and PEA) indicate strong metabolic associations. Together with our recent findings of elevated basal 2-AG levels in dependent cocaine users, present results indicate substance-specific alterations of the ECS that may have implications in the search for novel therapeutic interventions for these populations