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ZUSAMMENFASSUNGDiskutiert wird der Fall eines 41-jährigen Piloten ohne relevante psychiatrische Vorgeschichte, der im Kontext einer gesicherten COVID-Infektion mit Kopfschmerzen, Müdigkeit und Antriebsbarmut zeitgleich eine ängstlich-paranoide Symptomatik mit Verfolgungs- und Beziehungsideen entwickelte, die über mehrere Wochen persistierte und unter Neuroleptikamedikation vollständig remittierte. Er blieb nach dem Absetzen der Medikation symptomfrei. Die Differenzialdiagnose einer polymorphen psychotischen Störung wurde im Verlauf in die Diagnose einer organischen wahnhaften Störung geändert. Neurostatus, CCT, Liquor und EEG waren unauffällig. Die diagnostische Einordnung des Störungsbildes hat für die Beurteilung der Berufsfähigkeit des Probanden große Bedeutung. Differenzialdiagnostische Aspekte werden diskutiert.

The rising number of people using methamphetamine leads to an increasing need for treatment options for this patient group. Evidence-based research on the efficacy of treatment programs for methamphetamine users is limited. Due to specific characteristics of methamphetamine users, the question arises whether established treatment methods for individuals using other substances can be effective for the treatment of methamphetamine dependence as well. We hypothesize that there are significant differences between the two groups that may affect the effectiveness of treatment and worsen the prognosis of treatment outcomes for methamphetamine users compared to consumers of other substances.To investigate potential differences in cognitive functioning and psychopathology between methamphetamine users and other substance users and possible correlations with treatment outcomes.A total of 110 subjects were recruited for an observational, longitudinal study from a German inpatient addiction treatment center: 55 patients with methamphetamine dependence and 55 patients with dependence of other substances ("OS group"). Both groups were examined at beginning (baseline) and end of treatment (after 6 mo) with regard to treatment retention, craving, cognitive functioning, psychosocial resources, personality traits, depression, and other psychiatric symptoms. Instruments used were Raven's IQ test, Mannheimer craving scale, cognitrone cognitive test battery, NEO personality factors inventory, Hamilton depression scale, Becks depression inventory, and a symptom checklist. The statistical methods used wereA total drop-out rate of 40% (methamphetamine-group: 36.4%; OS-group: 43.6%) was observed without significant differences between groups. At baseline, methamphetamine-group subjects significantly differed from OS-group individuals in terms of a lower intelligence quotient, fewer years of education, slower working speed, and decreased working accuracy, as well as less cannabinoid and cocaine use. Methamphetamine-group subjects further showed a significantly lower score of conscientiousness, depressive, and psychiatric symptoms than subjects from the OS-group. In both groups, a reduction of craving and depressive symptoms and an improvement of working speed and working accuracy was noted after treatment.There are differences between methamphetamine users and users of other drugs, but not with regard to the effectiveness of treatment in this inpatient setting. There are differences in cognitive function and psychopathology between methamphetamine and other drugs users. The existing treatment options seem to be an effective approach in treating methamphetamine dependence.

ZusammenfassungOpiatabhängigkeit ist bei Straftätern häufig und viele opiatabhängige Rechtsbrecher werden nach § 64 STGB im Maßregelvollzug behandelt. Während die Substitutionsbehandlung in Haftanstalten mittlerweile gängige Praxis ist, wird die Substitutionsbehandlung im traditionell abstinenzorientierten Maßregelvollzug sehr kontrovers und regional auch unterschiedlich gesehen. Basisdaten dazu fehlen bislang. Vor dem Hintergrund eines aktuellen Gutachtensfalles wird die Problematik dargestellt. Aktuelle Zahlen aus einer großen Forensischen Klinik in München-Ost zeigen, daß knapp 30% der dort behandelten Patienten substituiert werden (N=186). Die Problematik der Substitutionsbehandlung im Maßregelvollzug disktutiert.

Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of SAMM50 was linked to HCC. We aimed to validate this finding in a large cohort of patients with advanced alcoholic liver disease (ALD). A large, well-characterised cohort of patients with alcoholic cirrhosis without (n = 674) and with (n = 386) HCC, as well as controls with HCC due to viral hepatitis (n = 134), controls with heavy alcohol abuse without liver disease (n = 266) and healthy subjects (n = 237), were genotyped for SAMM50 rs3827385 and rs3761472 and for PNPLA3 rs738409. Genotype frequencies were compared between patients with alcohol-associated cirrhosis with and without HCC by uni- and multivariate analysis. Minor variants in both SAMM50 rs3827385 and rs3761472 were significantly more frequent in patients with alcoholic HCC versus alcoholic cirrhosis and versus the control cohorts. An even stronger association was noted for PNPLA3 rs738409. The univariate analysis resulted in an odds ratio (OR) of 1.8 for carriers of at least one minor variant of SAMM50 rs3827385 and rs3761472 (each p < 0.001), but this association was lost in multivariate analysis with age (OR 1.1/year), male sex (OR 3.2), diabetes (OR 1.9) and carriage of PNPLA3 148M (OR 2.1) remaining in the final model. Although minor variants of both SAMM50 loci are strongly associated with alcoholic HCC, this association is not independent of carriage of the well-known risk variant PNPLA3 148M.

Hepatocellular carcinoma (HCC) is a severe complication of advanced alcoholic liver disease, which is modulated by genetic predisposition. Identifying new genetic loci might improve screening. Genetic variation of

Oral methadone or sublingual buprenorphine are first-line medications for pharmacotherapy of opioid use disorders (OUDs). Three long-acting buprenorphine depot or implant formulations are currently available for the treatment of OUDs: (1) CAM 2038 (Buvidal) for subcutaneous weekly and monthly application; (2) RBP-6000 (Sublocade™) as a monthly depot formulation; and (3) A six-month buprenorphine implant [Probuphine™]. The pharmacology, clinical efficacy and prospects of these medications are discussed.

ZUSAMMENFASSUNGPharmakologisches Neuroenhancement (PN) beschreibt die Einnahme diverser psychotroper Substanzen zur geistigen Leistungssteigerung, ohne dass dafür eine medizinische Notwendigkeit bestünde. Dazu werden vor allem Stimulanzien (Methylxanthintyp wie Koffein und Amphetamintyp wie Methylphenidat, Amphetamine) sowie Nichtstimulanzien (z. B. Antidementiva, Antidepressiva und Phytopharmaka wie Ginkgo biloba) sowie Modafinil ge- bzw. missbraucht. Auch wenn die rechtliche Situation facettenreich ist, indiziert die Einnahme von Substanzen, die zum PN eingenommen werden, nicht stets die Anwendung des Strafrechts. Sowohl die indikationslose Einnahme von frei erhältlichen Over-the-Counter-Drugs (OTC-Drugs) sowie verschreibungspflichtigen Substanzen als auch von Betäubungsmitteln ist bislang weitgehend straffrei.

ZUSAMMENFASSUNGNur wenige Substanzen sind als sogenannte Anti-Craving-Me-dikamente zur pharmakogestützten Rückfallprophylaxe der Alkoholabhängigkeit zugelassen. Dazu gehören das in Deutschland nicht mehr vertriebene Disulfiram, die Opioidantagonisten Naltrexon und Nalmefen sowie Acamprosat. Gerade für Acamprosat und Naltrexon ist die Evidenzbasierung recht gut, bei mäßiger, aber klinisch signifikanter Effizienz. Sie werden trotzdem selten eingesetzt. Interessante Substanzen mit klinischer Perspektive sind am ehesten Baclofen, Vareniclin und Gabapentin. Die klinischen Befunde und Perspektiven der Pharmakotherapie bei Alkoholabhängigkeit werden dargestellt.

ZUSAMMENFASSUNGMissbrauch und Abhängigkeit von Sedativa und Hypnotika sind klinisch häufig (Prävalenz ca. 2%), insbesondere von Benzodiazepinen und Non-Benzodiazepin-Hypnotika (Z-Drugs). Beide Substanzgruppen haben ältere und weit toxischere Sedativa und Hypnotika wie Barbiturate und Meprobamat zu Recht verdrängt. Benzodiazepine wie Z-Drugs entfalten ihre Wirkung über den inhibitorischen GABA-Rezeptor und können beide eine erhebliche Toleranz induzieren, was klinisch zu Dosissteigerungen, physischer und psychischer Abhängigkeit, Kontrollverlust sowie Entzugssymptomen führen kann. Prädisponierende Faktoren sind neben dem Geschlecht, Frauen sind häufiger betroffen, vor allem psychiatrische und psychosomatische Erkrankungen, insbesondere Angst und Schlafstörungen, aber auch psychosomatische Störungen und chronische Schmerzerkrankungen. Besonders häufig und lange werden Benzodiazepine älteren Patienten verschrieben, entgegen aller Leitlinienempfehlungen.Therapeutisch gesichert ist, dass bei Benzodiazepinabhängig-keit ein langsames Ausschleichen über viele Wochen, manchmal sogar Monate notwendig ist. Ansonsten können erhebliche Entzugserscheinungen inklusive epileptischen Anfällen, Psychosen und Delire auftreten. Das Entzugssyndrom bei Sedativa und Hypnotika ist sehr vielgestaltig mit Depression, Agitation, innerer Unruhe und Perzeptions-und Schlafstörungen als häufigen Symptomen. Die übrige Therapie ist pragmatisch und richtet sich nach den zugrunde liegenden psychischen Störungen und Entzugssymptomen. Im Wesentlichen werden Antidepressiva eingesetzt. Kurzzeitinterventionen werden empfohlen. Psychotherapeutisch haben sich Psychoedukation, kognitive Verhaltenstherapie oder motivationale Therapien bewährt.

In Germany, the prevalence rates for alcohol use disorders amount to approx. 6%, while about 3% are diagnosed as being alcohol dependent. Only 10% of the patients are undergoing treatment. There are apparent deficits with respect to early interventions. The internet presence of "Ohne Alkohol mit Nathalie" (OAmN) (Abstinence with Nathalie) ameliorates options for early treatment interventions using a web-based design; however, this intervention has not been evaluated to date, especially with respect to previous treatments.Over a 4-week period, 4 different channels of OAmN posted announcements for a survey participation introducing a link leading to a web-based survey questionnaire on the domain oamn.jetzt. The questionnaire offered open and closed as well as multiple choice questions regarding alcohol use patterns and attempts to change the problematic drinking behavior.Out of 2022 participants 84.3% (n = 1705) stated to have or have had a problem with alcohol use, 17.7% (n = 302) had a diagnosis of alcohol dependence by a physician or psychologist and only 21% (n = 529) had been in therapy before. The majority of responders (85.5%, n = 1457) had stopped alcohol use before participating in the survey. Most of them (48.5%, n = 705) were assisted by OAmN, 97.5% (n = 1662) had been employed while having the abovementioned problem use of alcohol, 34.3% (n = 570) rated their job performance as "very good" and 43.2% (n = 718) as "good".This pilot study revealed that OAmN can reach people affected by problematic drinking behavior who had not been in contact with the professional medical system for addiction treatment despite having a problematic alcohol use combined with the willingness to quit.EINLEITUNG: Die Prävalenzraten für Alkoholgebrauchsstörungen liegen in Deutschland bei ca. 6 %, alkoholabhängig sind ca. 3 %. Nur ca. 10 % der Patienten befinden sich in suchtmedizinischer Therapie. In der Früherkennung und -intervention besteht zudem eine deutliche Unterversorgung. Eine bislang nicht evaluierte Ergänzung zu bestehenden Interventionsangeboten ist der außerhalb der professionellen Suchthilfe von einer ehemaligen Betroffenen entwickelte Internetauftritt „Ohne Alkohol mit Nathalie“ (OAmN). Die vorliegende Pilotstudie hatte zum Ziel, herauszufinden, ob die Nutzer der OAmN-Angebote zu jenen zählen, die bisher vom Suchthilfesystem nicht erreicht werden konnten.Innerhalb von vier Wochen wurden Nutzer auf vier verschiedenen OAmN-Kanälen dazu aufgerufen, sich an einer anonymen Befragung zu beteiligen. Ein Link führte jeweils zu einem webbasierten Fragebogen. Dieser umfasste offene, geschlossene sowie Multiple-Choice-Fragen zum Konsummuster von Alkohol und bisherigen Therapiebemühungen.Von 2022 Teilnehmern gaben 84,3 % (n = 1705) an, ein „Alkoholproblem“ zu haben oder es gehabt zu haben. Davon hatten 17,7 % (n = 302) die Diagnose einer Alkoholabhängigkeit und 21 % (n = 529) Therapieerfahrung. Sistiert hatten ihren Alkoholkonsum zum Zeitpunkt der Befragung 85,5 % (n = 1457) der Betroffenen. Die meisten davon (48,5 %, n = 705) mithilfe von OAmN. 97,5 % (n = 1662) waren während ihrer Konsumzeit berufstätig und haben aus eigener Sicht zu 34,3 % (n = 570) „sehr gut“, zu 43,2 % (n = 718) „gut“ funktioniert.Die Pilotstudie zeigt, dass webbasierte Angebote wie OAmN Menschen erreichen können, die durch Angebote des etablierten Suchthilfesystems nicht erreicht werden, obwohl eine alkoholbezogene Störung vorliegt und eine Bereitschaft zur Verhaltensänderung im Hinblick auf den Alkoholkonsum besteht.

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

International audience; Introduction - Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. Methods - We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. Results - The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10) and higher premorbid body mass index (26.37 ± 0.16 kg/m) than controls (24.44 ± 0.18 kg/m, P = 5.77 × 10). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. Discussion - If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

Die Substitutionstherapie mit langwirksamen Opioiden hat eine herausragende Bedeutung fur die Behandlung und Versorgung von Menschen mit Opiatabhangigkeit. Das Spektrum der einsetzbaren Substanzen hat sich in der letzten Zeit deutlich erweitert, wodurch sich die Prognose fur Opiatabhangige erheblich verbessert hat.

ZusammenfassungBislang sind nur wenige Medikamente zur pharmakologischen Rückfallprophylaxe der Alkoholabhängigkeit zugelassen. Neben dem in Deutschland nicht mehr vertriebenen Disulfiram sind es die Opioidantagonisten Naltrexon und Nalmefen sowie das vermutlich über glutamaterge Neurone wirkende Acamprosat. Baclofen und γ‑Hydroxybutyrat (GHB) sind in einzelnen Ländern zugelassen. Wirkstoffe wie z. B. Vareniclin, Gabapentin und Topiramat können für die Rückfallprophylaxe der Alkoholabhängigkeit von Interesse sein, jedoch ist bislang keine Zulassung erfolgt. Vor dem Hintergrund der zur Revision anstehenden S3-Leitlinie zur Diagnose und Behandlung alkoholbezogener Störungen wird der heutige Kenntnisstand zur Pharmakotherapie der Alkoholabhängigkeit dargestellt.

Comorbidity of bipolar disorder (BD) and alcohol use disorder (AUD) is very frequent resulting in detrimental outcomes, including increased mortality. Diagnosis of AUD in BD and vice versa is often delayed as symptoms of one disorder mimic and obscure the other one. Evidence for pharmacotherapies for people with comorbid BD and AUD remains limited, and further proof-of-concept studies are urgently needed.This paper explores the currently available pharmacotherapies for AUD, BD and their usefulness for comorbid BD and AUD. It also covers to some degree the epidemiology, diagnosis, and potential common neurobiological traits of comorbid BD and AUD.The authors conclude that more controlled studies are needed before evidence-based guidance can be drawn up for clinician's use. Since there are no relevant pharmacological interactions, approved medications for AUD can also be used safely in BD. For mood stabilization, lithium should be considered first in adherent persons with BD and comorbid AUD. Alternatives include valproate, lamotrigine, and some atypical antipsychotics, with partial D2/D3 receptor agonism possibly being beneficial in AUD, too.

Opiate addiction is common among offenders, and many opiate-dependent lawbreakers are treated in the correctional system according to § 64 STGB. While substitution treatment in prisons has become common practice, substitution treatment in forensic hospitals in the traditionally abstinence-oriented prison system is controversial and also varies from region to region. Basic data on this are lacking so far. The problem is discussed against the background of a current expert opinion case. Current figures from a large forensic hospital in Munich-East show that almost 30% of the patients are treated with substitutes (n=186). The problem of substitution treatment in the prison system is discussed.Opiatabhängigkeit ist bei Straftätern häufig und viele opiatabhängige Rechtsbrecher werden nach § 64 STGB im Maßregelvollzug behandelt. Während die Substitutionsbehandlung in Haftanstalten mittlerweile gängige Praxis ist, wird die Substitutionsbehandlung im traditionell abstinenzorientierten Maßregelvollzug sehr kontrovers und regional auch unterschiedlich gesehen. Basisdaten dazu fehlen bislang. Vor dem Hintergrund eines aktuellen Gutachtensfalles wird die Problematik dargestellt. Aktuelle Zahlen aus einer großen Forensischen Klinik in München-Ost zeigen, daß knapp 30% der dort behandelten Patienten substituiert werden (N=186). Die Problematik der Substitutionsbehandlung im Maßregelvollzug disktutiert.

Methamphetamine use disorder is associated with severe psychiatric symptoms and psychosocial problems. Women seem to be more affected than men. Therefore, this study examined psychiatric comorbidities and psychopathology, drug use patterns, and treatment outcomes in women addicted to methamphetamine compared to men. Data on methamphetamine-dependent inpatients were collected in two centers specialized for addiction treatment at admission (T0) and discharge (T1, after treatment for 24 weeks). Sociodemographic and clinical measures were collected with the semi-structured clinical interview I at baseline; the self-reported standardized questionnaire (SCL-90-R) was administered at admission and discharge and after 24 weeks. During the entire treatment procedure, treatment relevant aspects were monitored. Out of all 108 treatment-seeking participants (86 men, 22 women), 64 completed the study (51 men, 13 women; drop-out rate: 40.7% (n = 44)). Methamphetamine-dependent women used other stimulants more often than men, while men used hallucinogens significantly more frequently than women. Female inpatients differed significantly from men in various sociodemographic variables (e.g., having children, single parenting) and were significantly more often affected by current (p p p

Background: Previous genome-wide association studies (GWAS) identified genome-wide significant risk loci in chronic pancreatitis and investigated underlying disease causing mechanisms by simple overlaps with expression quantitative trait loci (eQTLs), a procedure which may often result in false positive conclusions. Methods: We conducted a GWAS in 584 non-alcoholic chronic pancreatitis (NACP) patients and 6040 healthy controls. Next, we applied Bayesian colocalization analysis of identified genome-wide significant risk loci from both, our recently published alcoholic chronic pancreatitis (ACP) and the novel NACP dataset, with pancreas eQTLs from the GTEx V8 European cohort to prioritize candidate causal genes and extracted credible sets of shared causal variants. Results: Variants at the CTRC (p = 1.22 × 10−21) and SPINK1 (p = 6.59 × 10−47) risk loci reached genome-wide significance in NACP. CTRC risk variants colocalized with CTRC eQTLs in ACP (PP4 = 0.99, PP4/PP3 = 95.51) and NACP (PP4 = 0.99, PP4/PP3 = 95.46). For both diseases, the 95% credible set of shared causal variants consisted of rs497078 and rs545634. CLDN2-MORC4 risk variants colocalized with CLDN2 eQTLs in ACP (PP4 = 0.98, PP4/PP3 = 42.20) and NACP (PP4 = 0.67, PP4/PP3 = 7.18), probably driven by the shared causal variant rs12688220. Conclusions: A shared causal CTRC risk variant might unfold its pathogenic effect in ACP and NACP by reducing CTRC expression, while the CLDN2-MORC4 shared causal variant rs12688220 may modify ACP and NACP risk by increasing CLDN2 expression.

Zusammenfassung Hintergrund In Europa gab es in den letzten 15 Jahren mehrere Schädlichkeits-Vergleiche bezüglich der Einnahme von psychotropen Substanzen durch Suchtexperten. Eine einzige Einschätzung liegt bezüglich des potenziellen Nutzens vor. Non-Opioiderge Analgetika (NOA), wie Gabapentinoide und NSARs, die zunehmend Gegenstand von Missbrauchsberichten sind, wurden bei solchen Rankings bisher nicht berücksichtigt. Ebenso existiert bisher keine multisubstanzbezogene Einschätzung darüber, ob sich die Beurteilung der Schädlichkeit einer illegalen Rauschdroge nach Änderung des Rechtsstatus in Deutschland ebenfalls ändern könnte. Studienziel und Methodik Anhand eines Fragebogens wurden 33 psychoaktive Substanzen inklusive Analgetika im Hinblick auf ihre gesundheitliche und soziale Schädlichkeit sowie potenzielle Nützlichkeit für den Konsumenten und deren Umgebung / Gesellschaft („andere“) von 101 erfahrenen Suchtmedizinern (Kohorte 1) bewertet. Zudem untersuchte diese Kohorte, ob sich die Schädlichkeitsbeurteilung einer illegalen Substanz bei eventueller Legalisierung ändert. Um die durchschnittliche Gesamtschädlichkeit (Gesamtrisiko) einer Substanz zu erhalten, wurde in einer zweiten Erhebung (Kohorte 2, 36 erfahrene Suchtmediziner) die prozentuale Beteiligung einer jeden Dimension an der Gesamtschädlichkeit bestimmt. Schließlich wurden die durchschnittliche Nutzen- und Gesamtrisikoeinschätzungen aufeinander bezogen. Ergebnisse Verordnungsfähigen psychoaktiven Substanzen wie Analgetika, NOAs (inklusive Gabapentinoiden) und opioidergen Substitutionsmitteln wurde ein günstiges Nutzen-Schadens-Profil attestiert. Jeweils im Mittelfeld der Schädlichkeits- wie der Nützlichkeitsbeurteilung befanden sich Cannabis und Ketamin. Alkohol und Nikotin wurden wie die meisten illegalen Rauschdrogen unter den schädlichen und am wenigsten nützlichen psychoaktiven Substanzen eingeordnet, wobei Alkohol durchschnittlich schädlicher, aber auch nützlicher als Nikotin beurteilt wurde. Bei potenzieller Legalisierung wurde die Gesamtschädlichkeit der traditionellen illegalen Drogen Metamphetamin, Kokain, Heroin und Cannabis als signifikant vermindert beurteilt. Dies beruhte hauptsächlich auf unter diesen virtuellen Bedingungen günstigerer Beurteilung der Schäden für andere. Schlussfolgerung Verordnungsfähigen Substanzen inklusive opioidergen und nicht-opioidergen Analgetika sowie opioidergen Substitutionsmitteln wurde ein günstiges Nutzen-Schadens-Profil zugordnet. Ein diesbezüglich ungünstiges Profil erhielten Alkohol, Nikotin sowie traditionelle Drogen, mit Ausnahme von Cannabis und Ketamin. Die Gesamtschädlichkeit traditioneller Drogen würde sich mit virtueller genereller Legalisierung verringern, hauptsächlich durch Abnahme der Schäden für andere.

Methamphetamine use disorder is often associated with psychopathological symptoms and attention performance deficits. Little is known about the co-incidence of methamphetamine use disorders and attention deficit hyperactivity disorder in childhood. This study examines potential correlations between substance use patterns, psychopathological symptoms, and attention performance in methamphetamine-dependent inpatients with and without a history of attention deficit hyperactivity disorder in childhood. Sixty male and 16 female inpatients in two treatment centers were examined. Pre-treatment, participants were interviewed regarding socio-demographic characteristics, medical history, completed measurements for intellectual capability, and symptomology of attention deficit hyperactivity disorder in childhood. Pre- and post-treatment cognitive function and psychopathological symptoms were assessed. Among the study population, the prevalence of symptomology of attention deficit hyperactivity disorder in childhood was 43.4% (n = 33), with higher scores in females. Without gender differences, participants with childhood attention deficit hyperactivity disorder were significantly younger than non-affected participants and had started significantly earlier the use of methamphetamine, alcohol, tobacco, and cannabis. The groups did not differ regarding treatment outcomes. However, the group of individuals with symptoms of attention deficit hyperactivity disorder in childhood had significantly more psychiatric diagnoses (e.g. post-traumatic stress disorder) and was significantly more affected by psychopathological symptoms at pre-treatment than non-affected patients. In both groups, the presence of psychopathological symptoms tended to decrease at post-treatment. No significant differences were found with respect to intelligence and attention performance. Methamphetamine-dependent inpatients seem to be highly affected by symptoms of attention deficit hyperactivity disorder in childhood, substance use disorders, and further psychopathological symptoms. This should be addressed in the establishment of new therapeutic programs.

International audience; BACKGROUND and AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to eight genetic loci identified previously as associated with alcohol-related cirrhosis and three clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of three single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated for cirrhosis risk. The odds ratio (OR) and 95% confidence intervals (CI) for the extreme score quintiles (Q1-Q5) of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18;8.60) (GenomALC-1); 2.81 (2.03;3.89) (GenomALC-2); and 3.10 (2.32;4.14) (UK Biobank). Patients with diabetes and high-risk score, compared to those without diabetes and a low-risk score, had ORs increased to 14.7 (7.69;28.1) (GenomALC-1) and 17.1 (11.3;25.7) (UK Biobank). Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76±0.06 versus 0.61±0.02, p=0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on three genetic risk variants and diabetes status can provide meaningful risk stratification for cirrhosis in excess drinkers, allowing earlier prevention planning including intensive intervention. LAY SUMMARY: Excessive chronic drinking leads to liver cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. Our study has developed a genetic risk score (GRS) test that can identify patients at high risk and shows that the risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and high GRS. Risk assessment using this test has potential for early and personalised management of this disease in high-risk patients.

ZusammenfassungDie Opioidsubstitution mit Methadon (oral) oder Buprenorphin (sublingual) ist eine etablierte weltweit praktizierte First-Line-Behandlung der Opiatabhängigkeit. Beide Substanzen müssen täglich oder zumindest alle 2 Tage (Buprenorphin) gegeben werden. Langwirksame Opioide standen zur Substitution nicht zur Verfügung. Das ändert sich jetzt mit dem bereits zugelassenen, wöchentlich oder monatlich subkutan injizierbaren Buprenorphin Depot CAM 2038 (Buvidal®), dem monatlich zu applizierenden Depotpräparat RBP-6000 (Sublocade™) und dem 6-Monate wirkenden Buprenorphin Depot-Implantat (Probuphine™). Klinische Befunde und mögliche Indikationen dieser Medikamente werden diskutiert.

Introduction: Opioid addiction is a worldwide disease with a significant impact. A multitude of physical and mental comorbidities are associated with opioid addiction, pain being one of the most relevant. Insufficient pain management may lead to a disruption in medical treatment, self-medication, and subsequent harm to patients. Areas covered: In this review, the authors provide a general overview of opioid addiction. A literature search for pain management and opioid maintenance treatment was conducted. Different settings of acute or chronic pain and situations specific to patients addicted to opioids are described. Pain management therapy in addiction is also addressed with an emphasis on treatment strategies such as the optimization of methadone and buprenorphine medication, additional opioid analgesia, and multimodal pain management. Expert opinion: Opioid addiction is a growing global health concern, and maintenance therapy remains an effective and lifesaving treatment option. However, there remains uncertainty on the appropriate pain management for this patient group. The backbone of pain management in opiate-addicted patients remains maintenance therapy while adjunctive treatment such as regional analgesia, non-opioid analgesia, antidepressants, steps to improve sleep, acceptance and commitment therapy, biofeedback, and hypnosis should be considered. Additional opioid medication is possible as well.

Die Opioidsubstitution mit Methadon oder Buprenorphin ist eine anerkannte, weltweit praktizierte First-line-Behandlung der Opioidabhangigkeit. Neben dem in Deutschland bereits verfugbaren wochentlich oder monatlich subkutan injizierbaren Buprenorphin Depot CAM 2038 (Buvidal®) stehen mit dem monatlich zu applizierenden Depotpraparat RBP-6000 (Sublocade™) und dem 6 Monate wirkenden Buprenorphin-Depot-Implantat (Probuphine™) demnachst wahrscheinlich mehrere langzeitwirksame Buprenorphinformulierungen zur Verfugung. Der bisherige Wissensstand und mogliche Einsatzgebiete dieser Praparate werden diskutiert.