Alkohol und Spielen - same same but different

Mit Hilfe der vorliegenden sechs Arbeiten dieser Habilitationsschrift sind neue Erkenntnisse zu Ähnlichkeiten und Unterschieden zwischen stoffgebundenen und stoffungebundenen Süchten erbracht worden. Alkohol und Spielen - same same but different. Hierzu wurden Studien bezüglich Familienanamnese für Alkoholabhängigkeit, Folgen von Rauschtrinken bei Jugendlichen, Nalmefen, einer pharmakologischen Behandlungsmöglichkeit, sowie PET-Studien mit unterschiedlichen Radioliganden zu pathologischem Glücksspiel herangezogen. Es konnte gezeigt werden, dass Probanden mit einer positiven Familienanamnese für Alkoholabhängigkeit im experimentellen i.v.-Alkohol-Selbstverabreichungsverhalten höhere Spiegel als Probanden mit negativer Familienanamnese präferieren. Auch auf Grundlage früherer Studien kann dies ein weiterer wichtiger Aspekt zur Klärung von Faktoren für die spätere Entwicklung einer alkoholbezogenen Störung sein. Eine retrospektive Aktenrecherche zu alkoholintoxikationsbedingten stationären Aufnahmen bei Jugendlichen erbrachte einen Geschlechterunterschied bezüglich alkohol-bedingter Beeinträchtigung (ABB), ein Maß, das einfach aus zwei klinischen Parametern (BAC und GCS) berechnet werden und zur möglichen Beurteilung der Entwicklung einer späteren Alkoholabhängigkeit herangezogen werden kann. Verändertes Belohnungsverhalten als ein Merkmal von Abhängigkeitserkrankungen konnte in einer fMRT-Studie unter Alkoholeinfluss nach einer Einzeldosis Nalmefen bei alkoholabhängigen Probanden ohne Therapiemotivation modifiziert werden. Dies liefert erste Erklärungen für zugrundeliegende neurobiologische Nalmefen-Effekte. Eine 11C-Carfentanyl-PET-Replikations-Studie erbrachte die Bestätigung, dass eine orale pharmakologische Amphetamin-Challenge in Kombination mit 11C-Carfentanyl-PET eine gute Möglichkeit bietet, psychiatrische Erkrankungen, bei denen das Opiatsystem eine zentrale Rolle einnimmt, zu charakterisieren. Auf Grundlage derer konnte mit einer 11C-Carfentanyl-PET-Studie mit Amphetamin-Challenge bei Probanden mit pathologischem Glücksspiel eine gedämpfte endogene Opioid-Freisetzung bei zugleich im Gegensatz zu stoffgebundene Süchten fehlender erhöhter Baseline μ-Opiatrezeptor-Verfügbarkeit nachgewiesen werden. Auch im GABAergen System bei Probanden mit pathologischem Glücksspiel konnten mithilfe von 11C-Ro15-4513-PET Unterschiede zu stoffgebundenen Süchten gezeigt werden. Bei gleichzeitig positiver Korrelation mit stimmungsbezogener Impulsivität zeigte sich im rechten Hippocampus eine erhöhte 11C-Ro15-4513-Bindungsaffinität im Vergleich zu gesunden Probanden. In früheren Studien zu stoffgebundenen Süchten war eine verminderte 11C-Ro15-4513-Bindungsaffinität nachgewiesen worden

New Approaches in Drug Dependence: Opioids

Purpose of Review: This article aims to provide an overview of standard and adjunctive treatment options in opioid dependence in consideration of therapy-refractory courses. The relevance of oral opioid substitution treatment (OST) and measures of harm reduction as well as heroin-assisted therapies are discussed alongside non-pharmacological approaches. Recent Findings: Currently, recommendation can be given for OST with methadone, buprenorphine, slow-release oral morphine (SROM), and levomethadone. Heroin-assisted treatment using diamorphine shall be considered as a cost-effective alternative for individuals not responding to the afore-mentioned opioid agonists in order to increase retention and reduce illicit opioid use. The modalities of application and the additional benefits of long-acting formulations of buprenorphine should be sufficiently transferred to clinicians and the eligible patients; simultaneously methods to improve planning of actions and self- management need to be refined. Regarding common primary outcomes in research on opioid treatment, evidence of the effectiveness of adjunctive psychological interventions is scarce. Summary: Maintaining a harm reduction approach in the treatment of opioid addiction, a larger range of formulations is available for the prescribers. Embedding the pharmacological, ideally individualized treatment into a holistic, structure-giving concept also requires a reduction of fragmentation of ancillary services available, drug policies, and treatment philosophies on a global scale

Adolescent women induce lower blood alcohol levels than men in a laboratory alcohol self-administration experiment

Background Adolescence is a critical period for the development of alcohol use disorders; drinking habits are rather unstable and genetic influences, such as male sex and a positive Family History of alcoholism (FH), are often masked by environmental factors such as peer pressure. Methods We investigated how sex and FH modulate alcohol use in a sample of 18-19-year-olds from the Dresden Longitudinal Study on Alcohol use in Young Adults (D-LAYA). Adolescents reported their real-life drinking in a TimeLine Follow-Back (TLFB) interview. They subsequently completed a training and an experimental session of free-access intravenous Alcohol Self-Administration (i.v. ASA) using the computer-assisted alcohol infusion system in order to control for environmental cues as well as for biological differences in alcohol pharmacokinetics. During i.v. ASA, we assessed subjective alcohol effects at eight time points. Results Women reported significantly less real-life drinking than men and achieved significantly lower mean arterial Blood Alcohol Concentrations (aBACs) in the laboratory. At the same time, women reported greater sedation relative to men and rated negative effects as high as did men. A positive FH was associated with lower real-life drinking in men but not in women. In the laboratory, FH was not linked to i.v. ASA. Greater real-life drinking was significantly positively associated with higher mean aBACs in the laboratory, and all i.v. ASA indices were highly correlated across the two sessions. Conclusions We conclude that adolescent women chose lower aBACs because they experienced adverse alcohol effects, namely sedation and negative effects, at lower aBACs than men. A positive FH was not apparent as risk factor for drinking in our young sample. The i.v. ASA method demonstrated good external validity as well as test-retest reliability, the latter indicating that a separate training session is not required when employing the i.v. ASA paradigm

Psychedelic Experiences During the Early COVID-19 Pandemic: Findings From an International Online Survey

Introduction: The current corona virus disease (COVID-19) pandemic has caused a serious global health crisis that has affected large parts of the public and private life worldwide, including the use of psychoactive substances. In this study, we investigated the effect of the COVID-19 pandemic on the use of serotonergic psychedelics, i.e., the settings in which people use psychedelics, the motives of usage, and the subjective quality of psychedelic experiences. Methods: The study was part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages (English, German, Spanish, Italian, and Korean) carried out during the early phase of the pandemic from April to August 2020. Participants were asked to retrospectively rate settings and motives of psychedelic substance use before the pandemic and in the last 4 weeks during the pandemic, as well as changes in psychedelic experiences. Results: Of n = 1,375 participants that reported the use psychedelics in 2019 or 2020, n = 642 (46.6%) also took psychedelics during the pandemic. During the pandemic, participants used psychedelics significantly less often in settings that were outside their home. Top motives to use psychedelics were comparable before and during the pandemic, but participants consumed less out of curiosity, to celebrate, or because friends took it, and more out of boredom. An increase in positively connoted, often pro-social experiences was observed. Two thirds of participants who used psychedelics during the pandemic claimed that psychedelics had helped them to deal better with the corona pandemic at least slightly. Discussion: Changes in setting and motives were mostly in line with restrictions caused by control measures to contain the spread of the virus. The unexpected increase in positively connoted experiences possibly reflects a favorable interaction of environmental macro- and individual micro-contexts during the pandemic (e.g., by reducing the use in more uncontrolled recreational settings or by encouraging a strong self-selection of substance users due to the expectation of "bad trips"). Increased pro-social feelings under psychedelics might reflect a desire for social interactions in times of social distancing and pandemic-related stress and anxiety

Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in laboratory experiments involving computer-assisted self-infusion of ethanol (CASE)

Rationale: Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls. Objectives: To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls. Materials and methods: Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party. Results: The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants. Conclusions: This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration

Predictors of Alcohol Consumption Among Younger Adults During the First Phase of the COVID-19 Pandemic

Background: The COVID-19 pandemic may lead to negative mental health effects but the effect on alcohol consumption among younger adults is unclear. We assess predictors of change in alcohol consumption during the first phase of the COVID-19 pandemic among younger adults. Methods: This cross-sectional internet-based survey was part of an overarching project, the Corona Drug Survey, which was conducted from April 30 to August 4, 2020. Participants of any sex and >= 18 years old were included. The primary outcome measure was change in alcohol consumption during the early COVID-19 pandemic. We implemented an ordinal logistic regression to assess the effect (odds ratio [OR] and 95% confidence interval [CI]) of the following predictors: quarantine restrictions on leaving the residence, number of individuals in the household, problematic alcohol consumption before the pandemic (CAGE [cutting down, annoyance by criticism, guilty feeling, and eye-opener] score), personal concern regarding the pandemic, age, and sex. Results: 3,321 participants with a mean age of 32 (SD: 13) years were included in this study. 70.4% of participants reported less or unchanged alcohol consumption in the recent 4 weeks of the pandemic compared to before the pandemic. A higher number of individuals in the household was associated with a reduced alcohol consumption (OR = 0.869; 95% CI = 0.815-0.927). No quarantine restrictions on leaving the residence (OR = 1.593; 95% CI = 1.397-1.817), a higher age (1.006; 1.001-1.011), and female sex (compared to males: 1.206; 1.062-1.371) were associated with an increase in alcohol consumption. The CAGE score before the pandemic (OR = 0.983; 95% CI = 0.931-1.037) and the pandemic concern (0.927; 0.857-1.003) were not associated with a significant change in alcohol consumption. Celebrations were no longer frequent drinking occasions during the pandemic compared to before the pandemic. The majority of participants (60.9%) did not use alcohol drinking as a coping mechanism to mitigate negative effects of the pandemic. Interpretation: In this cohort of younger adults with fewer celebratory drinking occasions, restrictions on leaving the residence and the number of persons in the household were the strongest predictors of reduced alcohol consumption during the early phase of the pandemic.</p

Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

New Approaches in Drug Dependence: Opioids

Purpose of review!#!This article aims to provide an overview of standard and adjunctive treatment options in opioid dependence in consideration of therapy-refractory courses. The relevance of oral opioid substitution treatment (OST) and measures of harm reduction as well as heroin-assisted therapies are discussed alongside non-pharmacological approaches.!##!Recent findings!#!Currently, recommendation can be given for OST with methadone, buprenorphine, slow-release oral morphine (SROM), and levomethadone. Heroin-assisted treatment using diamorphine shall be considered as a cost-effective alternative for individuals not responding to the afore-mentioned opioid agonists in order to increase retention and reduce illicit opioid use. The modalities of application and the additional benefits of long-acting formulations of buprenorphine should be sufficiently transferred to clinicians and the eligible patients; simultaneously methods to improve planning of actions and self- management need to be refined. Regarding common primary outcomes in research on opioid treatment, evidence of the effectiveness of adjunctive psychological interventions is scarce.!##!Summary!#!Maintaining a harm reduction approach in the treatment of opioid addiction, a larger range of formulations is available for the prescribers. Embedding the pharmacological, ideally individualized treatment into a holistic, structure-giving concept also requires a reduction of fragmentation of ancillary services available, drug policies, and treatment philosophies on a global scale

Supervised on-site dosing in injectable opioid agonist treatment-considering the patient perspective. Findings from a cross-sectional interview study in two German cities

Abstract Background Injectable opioid agonist treatment (iOAT) is an effective option to support people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral OAT. However, iOAT has been criticised based on theoretical and practical grounds for its dosing policies: Current regulations demand supervised, on-site application and require patients to frequently visit their treatment facility. The current study aims to investigate how patients experience on-site application and derive strategies to enhance the acceptability and effectiveness of iOAT-delivery. Methods This article is based on semi-structured interviews with 27 individuals currently or previously in iOAT in two German outpatient iOAT-clinics. We undertook an inductive qualitative content analysis, which included blinded, independent coding and the analysis of individual cases. Results Comments regarding on-site application and daily visits to the clinic were grouped into positive and negative aspects, iOAT as the best alternative option, facilitators of daily visits, and suggestions for improvement. Positive aspects took the factors stability and social support in regard. Negative aspects ranged from general inconveniences to major impediments to individuals' daily lives and towards achieving psychosocial goals. Participants reported rigorous adherence to iOAT's treatment regime, often due to a perceived lack of alternative options. Meeting iOAT's demands was eased by the patients’ coping-strategies and through facilitating measures implemented by iOAT-clinics. Despite acknowledgement of the potential detriments from easing regulations, take-home arrangements were frequently suggested by participants to improve iOAT. Conclusions Being required to attend the clinic for supervised iOAT-application is not experienced uniformly. While clinics can support their patients to cope with strict regulations, alternative approaches to iOAT-application should be considered to accommodate patients' individual needs. Examples from other treatment modalities (e.g., remote supervision and delivery services) might aid to reconcile individualisation while providing adequate safety measures and improve iOAT in the long term