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Abstract Background Direct acting antivirals (DAAs) as a curative treatment of hepatitis C have been available for several years and have replaced interferon-containing therapies. However, treatment rates of people who inject drugs (PWID) are declining in Germany, putting the elimination of hepatitis C by 2030 at risk. This study aimed at elucidating the knowledge of, and attitude towards, hepatitis C treatment in a clinical sample of PWID. Methods Participants were recruited between February 2019 and October 2020 at two opioid agonist therapy (OAT) clinics and two in-patient drug detoxification wards. Based on the European Addiction Severity Index (Europ-ASI), a standardized interview focusing on: sociodemographic data, drug history, risky behavior, infection with hepatitis C virus (HCV) and HIV, and previous experience with HCV treatment was carried out. In addition, participants filled in a questionnaire evaluating 13 statements relating to HCV treatment (right/wrong) and 15 statements on their personal ‘pros and cons’ views to start such a treatment assessed with the means of a 6-point Likert scale. Results A total of 153 patients (average age 45 years, male 78%; 106 (69.3%) currently in opioid maintenance treatment, 47 (30.7%) currently admitted to an inpatient detoxification) with an opioid use disorder were investigated. All of them reported having injected drugs at least once in their lives; 97 participants (63.3%) stated that they had been previously diagnosed with HCV infection. Among them, 27/97 patients (27.8%) reported a previous treatment with interferon; 27/97 (27.8%) with DAAs; and 32/97 (33.0%) reported a currently active hepatitis C. Most patients knew about the availability and efficacy of DAAs. However, DAAs’ low rate of side effects, their short treatment duration, and their replacement of interferon, were not correctly evaluated by up to 50.3% of patients. 25–40% of 32 patients with currently active hepatitis C prioritized handling of social and other medical issues, e.g., reduction of heroin use, over treatment of hepatitis C. Conclusions Although current levels of risky behavior have reportedly been reduced by active PWID over the past few years, educational and motivational interventions to increase hepatitis C treatment uptake should address the gaps in patients’ knowledge.

Abstract Background Recent studies report that LGBTQ + people have experienced high levels of mental health problems during COVID-19-related social distancing. Given the well-established association between social isolation and mental health, the main aim of the current study was to investigate differences in mental health and (perceived) social isolation and social support in LGBTQ + individuals compared to heterosexual, cisgender people and to explore whether the hypothesized higher mental health burden in LGBTQ + individuals is (partly) mediated by (perceived) social isolation or social support. Methods N = 531 participants indicating belonging to the LGBTQ + community and N = 1826 not identifying as LGBTQ + participated in a cross-sectional online survey during the initial COVID-19-related lockdown in Germany. Standardized questionnaires were used to assess depression, anxiety, suicidality, loneliness and social support. Further, perceived social isolation and face-to-face communication during the lockdown were assessed. Results LGBTQ + people had higher levels of depression, anxiety and suicidal thought, were lonelier and experienced less social support than non-LGBTQ + identifying individuals. Mediation analysis showed that the higher levels of mental health burden in LGBTQ + people were (partly) mediated by reduced social connectedness. Further face-to-face contact positively affected mental health by reducing feelings of loneliness. Conclusion Given the high impact of loneliness on mental health, governmental actions should be taken to promote social connectedness particularly among LGBTQ + identifying individuals to ensure that the COVID-19 pandemic does not exacerbate the health inequalities that already exist between LGBTQ+-identifying and heterosexual, cisgender people.

Abstract Background Patients’ expectations toward any given treatment are highly important for the effectiveness of such treatment, as has been demonstrated for several disorders. In particular, in major depressive disorder (MDD), one of the most frequent and most serious mental disorders with severe consequences for the affected, the augmentation of available treatment options could mean a ground-breaking success. Repetitive transcranial magnetic stimulation (rTMS), a new, non-invasive, and well-tolerated intervention with proven effects in the treatment of MDD, appears particularly suitable in this context as it is assumed to exert its effect via structures implicated in networks relevant for both expectation and depression. Methods All patients will receive rTMS according to its approval. Half of the patients will be randomized to a psychological intervention, which is a comprehensive medical consultation aiming to improve positive treatment expectations; the control group will receive a conventional informed consent discussion (in the sense of a treatment-as-usual condition). As outcome parameters, instruments for both self-assessment and external assessment of depression symptoms will be applied. Furthermore, psycho-immunological parameters such as inflammation markers and the cortisol awakening response in saliva will be investigated. Resting-state functional magnetic resonance imaging (rs fMRI) will be performed to analyze functional connectivity, including the cerebellum, and to identify neuronal predictors of expectation effects. In addition, possible cerebellar involvement will be assessed based on a cerebellar-dependent motor learning paradigm (i.e., eyeblink conditioning). Discussion In this study, the effects of treatment expectations towards rTMS are investigated in patients with MDD. The aim of this study is to identify the mechanisms underlying the expectation effects and, beyond that, to expand the potential of non-invasive and well-tolerated treatments of MDD. Trial registration German Registry of Clinical Studies (DRKS DRKS00028017. Registered on 2022/03/07. URL: https://www.drks.de/drks_web/ .

BackgroundDuring the COVID-19 pandemic we assessed to which extent patients in opioid maintenance treatment (OMT) adhere to official recommendations regarding preventive intervention strategies against COVID-19.MethodsPatients enrolled in two OMT clinics in Germany were interviewed applying a standardized questionnaire, which covered socio-demographic information, recent psychotropic substance use, recent social activities, the history of SARS-CoV-2 infection, attitudes toward official protection recommendations, and levels of adherence to these suggestions. Current mental and medical diagnoses were retrieved from medical files. In subjects without known infection and without vaccination, blood samples were tested for the identification of anti-SARS-CoV-2-S-antibodies. Interviews were performed between the end of May and the end of September 2021.ResultsPatients’ (n = 155) average age was 47 years; 74% were males. In addition to the opiate dependence, in nearly 80% of cases another medical disorder was recorded. The range of medical factors that predispose for severe COVID-19 outcomes were present in 39% of patients; 18% of the sample refused to be vaccinated. Nearly all patients reported having carried out a range of activities outside their residence during the week prior to the interviews, including visits of treatment facilities (86.5%; 95% confidence interval [80.2%; 91.0%]) or meeting with friends (64.5% [65.7–71.6%]). Despite the fact that only about 47.1% [39.2%; 55%] felt well informed about measures against infection, adherence to COVID-19 countermeasures was generally high: 83.9% [77.3; 88.8%] claimed to have worn face masks always/nearly always; social distancing was performed always/nearly always by 58.7% [50.8%; 66.2%]; and hand hygiene was conducted by 64.5% [56.7%; 71.6%] of participants. None out of n = 25 tests from unvaccinated subjects was positive for anti-SARS-CoV-2-S-antibodies. Psychiatric comorbidity and educational degree were not statistically significantly associated with attitudes and compliance, except that patients with lower education felt relatively worse informed.ConclusionSelf-reported adherence to recommended non-therapeutic intervention strategies and vaccination rates were similar to the German general population. Provision of more health-related information tailored to OMT patients appears necessary.

Abstract Background The impact of COVID-induced stress on mental health and alcohol use has been demonstrated in recent research. However, there is a lack of longitudinal data since most studies reported on cross-sectional data. It remains unclear how alcohol use develops under the dynamic changes of the pandemic. Therefore, the present study aims to investigate the general development of alcohol use and the impact of COVID related stress on drinking behavior in a German population-based sample during the pandemic in 2020. Methods In the longitudinal design with three measurements (baseline [T1] and two follow-ups [T2, T3]) an online survey was administered. The survey included the Alcohol Use Disorder Identification Test (AUDIT) as well as the assessment of the drinking days in the last 30 days, the number of alcoholic beverages on each occasion and changes in alcohol use in the previous fourteen days. Further, COVID-19 related concerns, perceived stress, worries about friends and family and worries about the financial situation were also assessed and multiple linear regressions and confidence intervals (CI) were calculated. Results 1050 participants started the survey, 756 participants (71.4%), 317 (52.7%) participants completed the survey at all three measurements. Seventy six percent (n = 241) of the sample were female. An increase in alcohol use in the previous 14 days was reported by 10.9% at T1, 3.9% at T2 and 3.6% at T3. Moreover, a decrease in alcohol use in the previous 14 days was reported by 8.7% at T1, 6.5% at T2 and 4.1% at T3. The number of drinking days was significantly higher at T2 than at baseline (p

(1) Background: The clinical assessment of attention-deficit/hyperactivity disorder (ADHD) in adulthood is known to show non-trivial base rates of noncredible performance and requires thorough validity assessment. (2) Objectives: The present study estimated base rates of noncredible performance in clinical evaluations of adult ADHD on one or more of 17 embedded validity indicators (EVIs). This study further examines the effect of the order of test administration on EVI failure rates, the association between cognitive underperformance and symptom overreporting, and the prediction of cognitive underperformance by clinical information. (3) Methods: A mixed neuropsychiatric sample (N = 464, ADHD = 227) completed a comprehensive neuropsychological assessment battery on the Vienna Test System (VTS; CFADHD). Test performance allows the computation of 17 embedded performance validity indicators (PVTs) derived from eight different neuropsychological tests. Further, all participants completed several self- and other-report symptom rating scales assessing depressive symptoms and cognitive functioning. The Conners’ Adult ADHD Rating Scale and the Beck Depression Inventory-II were administered to derive embedded symptom validity measures (SVTs). (4) Results and conclusion: Noncredible performance occurs in a sizeable proportion of about 10% up to 30% of individuals throughout the entire battery. Tests for attention and concentration appear to be the most adequate and sensitive for detecting underperformance. Cognitive underperformance represents a coherent construct and seems dissociable from symptom overreporting. These results emphasize the importance of performing multiple PVTs, at different time points, and promote more accurate calculation of the positive and negative predictive values of a given validity measure for noncredible performance during clinical assessments. Future studies should further examine whether and how the present results stand in other clinical populations, by implementing rigorous reference standards of noncredible performance, characterizing those failing PVT assessments, and differentiating between underlying motivations.

Background: EEG biofeedback (NF) is an established therapy to enable individuals to influence their own cognitive-emotional state by addressing changes in brainwaves. Psycho-oncological approaches of NF in cancer patients are rare and effects are hardly studied. Objective: The aim of this explorative, randomized controlled trial was to test the effectiveness of an alpha and theta NF training protocol, compared to mindfulness based therapy as an established psycho-oncological treatment. Methods: Of initially 62 screened patients, 56 were included (inclusion criteria were cancer independent of tumor stage, age >18 years, German speaking; exclusion criteria suicidal ideation, brain tumor). Randomization and stratification (tumor stage) was conducted by a computer system. Participants got 10 sessions over 5 weeks, in (a) an NF intervention (n = 21; 13 female, 8 male; MAge = 52.95(10 519); range = 31 to 73 years)) or (b) a mindfulness group therapy as control condition (CG; n = 21; ie, 15 female, 6 male; MAge = 50.33(8708); range = 32 to 67 years)). Outcome parameters included self-reported cognitive impairment (PCI) as primary outcome, and secondary outcomes of emotional distress (DT, PHQ-8, GAD-7), fatigue (MFI-20), rumination (RSQ), quality of life (QoL, EORTC-30 QoL), self-efficacy (GSE), and changes in EEG alpha, and theta-beta band performance in the NF condition. Results: No changes in cognitive impairment were found ( P = .079), neither in NF nor CG. High affective distress was evident, with 70.7% showing elevated distress and 34.1% showing severe depressive symptoms. Affective symptoms of distress ( P ≤ .01), depression ( P ≤ .05) and generalized anxiety ( P ≤ .05) decreased significantly over time. No differences between NF and CG were found. There was a significant increase of the alpha band ( P ≤ .05; N = 15) over the NF sessions. Self-efficacy predicted QoL increase in NF with P ≤ .001 and an explained variance of 48.2%. Conclusion: This is the first study to investigate NF technique with regard to basic mechanisms of effectiveness in a sample of cancer patients, compared to an established psycho-oncological intervention in this field. Though there were no changes in cognitive impairment, present data show that NF improves affective symptoms comparably to mindfulness-based therapy and even more pronounced in QoL and self-efficacy. Trial registration: ID: DRKS00015773

Abstract Background This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. Methods We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. Results Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. Conclusions Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.

Abstract Background In the implementation of placement matching guidelines, feasibility has been concerned in previous research. Objectives of this process evaluation were to investigate whether the patient-centered matching guidelines (PCPM) are consistently applied in referral decision-making from an inpatient qualified withdrawal program to a level of care in aftercare, which factors affect whether patients actually receive matched aftercare according to PCPM, and whether its use is feasible and accepted by clinic staff. Methods The study was conducted as process evaluation within an exploratory randomized controlled trial in four German psychiatric clinics offering a 7-to-21 day qualified withdrawal program for patients suffering from alcohol dependence, and with measurements taken during detoxification treatment and six months after the initial assessment. PCPM were used with patients in the intervention group by feeding back to them a recommendation for a level of care in aftercare that had been calculated from Measurements in the Addictions for Triage and Evaluation (MATE) and discussed with the staff on the treatment unit. As measurements, The MATE, the Client Socio-Demographic and Service Receipt Inventory—European Version, a documentation form, the Control Preference Scale, and the Motivation for Treatment Scale were administered. A workshop for the staff at the participating trial sites was conducted after data collection was finished. Results Among 250 patients participating in the study, 165 were interviewed at follow-up, and 125 had received aftercare. Although consistency in the application of PCPM was moderate to substantial within the qualified withdrawal program (Cohen’s kappa ≥ .41), it was fair from discharge to follow-up. In multifactorial multinomial regression, the number of foregoing substance abuse treatments predicted whether patients received more likely undermatched (Odds Ratio=1.27; p=.018) or overmatched (Odds Ratio=0.78; p=.054) treatment. While the implementation process during the study was evaluated critically by the staff, they stated a potential of quality assurance, more transparency and patient-centeredness in the use of PCPM. Conclusions While the use of PCPM has the potential to enhance the quality of referral decision making within treatment, it may not be sufficient to determine referral decisions for aftercare. Trial Registration German Clinical Trials Register DRKS00005035 . Registered 03/06/2013.

BackgroundThere is a lack of benefit/harm assessments of illicit and licit psychoactive substances performed by substance-dependent users in comparison to addiction medicine experts.MethodsWe extended the analyses of substance harm/benefit assessments of German addiction medicine experts (N = 101), in parts reported recently in this journal [doi.org/10.3389/fpsyt.2020.59219], by the perspectives of substance-addicted persons. The same questionnaire as used for the abovementioned “experts-study” was handed out to inpatient detoxification or rehab treatment seeking German substance-dependent adults (N = 117) for a subsequent structured interview about harms and benefits of 33 new and traditional psychoactive substances comprising also prescription drugs.Results and discussionBoth, users and experts, ranked the traditional illicit psychoactive substances heroin, cocaine and amphetamines within the top overall harm level group. Synthetic cannabinoids, alcohol and benzodiazepine were in a subordinate top-harm level position. Both cohorts also ranked methadone, nicotine and cannabis within the midrange and buprenorphine as well as psychotropic mushrooms within the lowest harm level positions. Experiences with prescription drugs (including opioidergic analgesics and gabapentinoids), cathinones, GHB, methamphetamine and methylphenidate was not prevalent in our user population. The same applied to barbiturates, propofol, kratom, ayahuasca with nearly zero assessments for each substance. The most user-experiences (>50% per assessed substance) were reported with nicotine, cannabis, alcohol, cocaine, heroin, amphetamine and methadone (core group). The user’s overall harm ratings in terms of these psychoactive substances were similar to those of the experts with the exception of the methadone assessment which was rated by the experts to be significantly less harmful if compared with the users’ estimation (supposed “treatment bias” of experts). The users’ benefit ratings for the traditional illicit psychoactive substances, cannabis as well as for nicotine were significantly more positive in comparison to those of the experts (supposed “attraction bias” of users). Both, experts and users, ranked the harms arising from the use of alcohol or benzodiazepines (usually unregulated substances) higher than the harms caused by the use of methadone, cannabis or psychotropic mushrooms (regulated by most Western narcotic acts). Users attributed the most benefits to buprenorphine, methadone and cannabis. This might reflect a main limitation of the study as the data are from an user population comprising over 50% patients who sought detoxification-treatment of opiates where methadone and buprenorphine are usual transient medications (supposed “selection bias”).ConclusionThis study addressed current trends of psychoactive substance abuse (e.g., synthetic cannabinoids, prescription drugs) and provides from both perspectives (that of the user and that of the addiction medicine experts) robust harm/benefit evaluations at least of a core group of psychoactive substances (traditional illicit psychoactive substances, cannabis, methadone, alcohol and nicotine). The results of this study can be valuable to the psychoeducation of substance-addicted individuals and to current restriction/legalization debates, especially in the Western-EU.

The Research Domain Criteria (RDoC) approach seeks to understand mental functioning in continuous valid dimensions ranging from functional to pathological. Reward processing is a transdiagnostic functioning domain of the RDoC. Due to prototypical abnormalities, addictions are especially applicable for the investigation of reward processing. Subjective reward processing is challenging to determine and differs between genotypes of the catechol-O-methyltransferase gene (COMT) Val158Met polymorphism for incomparable daily life experiences. Thus, we implemented the monetary incentive delay (MID) task with comparable reward cues and visual analog scales (VAS) to assess subjective reward processing in male abstinent cannabis-dependent individuals (N = 13) and a control group of nicotine smokers (N = 13). COMT Val158Met genotypes were nominally associated with differences in cigarettes smoked per day and motivation in the MID Task (p = 0.028; p = 0.017). For feedback gain, activation of the right insula was increased in controls, and activation correlated with gain expectancy and satisfaction about gain. Subjective value is not detached from reward parameters, but is modulated from expectancy and reward by the insula. The underlying neural mechanisms are a fundamental target point for treatments, interventions, and cognitive behavioral therapy.

Abstract The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55–87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = − 0.042 (verbal fluency) and − 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI − 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55–65 years, 66–75 years, > 75 years). In the 66–75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

AIMS OF THE STUDY: Aftercare following inpatient withdrawal treatment improves the prognosis and prevents future readmissions in patients with substance use disorders. According to the stepped care approach, the setting and intensity of aftercare should be adjusted to the patients’ specific needs and resources. This study evaluated the real-life referral to different types of aftercare in Switzerland and the rate of inpatient readmission within a 1-year follow-up. METHODS: All substance use disorder patients admitted for inpatient withdrawal treatment in a Swiss psychiatric hospital between January and December 2016 (n = 497) were included in this retrospective study. Clinical and sociodemographic characteristics were extracted from the electronic medical records and their impact on the likelihood of being referred to a particular type of aftercare (general practitioner, psychiatric outpatient care, psychiatric day clinic, inpatient rehabilitation programme) was evaluated. For each type of referral, we determined the readmission rate within one year after discharge. RESULTS: In the sample of substance use disorder patients (mean age 41 years; 69% male), alcohol use disorder was by far the most frequent substance use disorder. Most patients were referred to psychiatric outpatient care (39.8%), followed by a general practitioner (31.0%), inpatient rehabilitation (19.3%) and psychiatric day clinic (9.9%). Patient characteristics that point to an unfavourable course of disease, including higher symptom severity, history of more than two previous admissions, compulsory admission and treatment discontinuation, were associated with a higher likelihood to be referred to lower-level aftercare (general practitioner, psychiatric outpatient care), whereas patients with lower symptom severity, fewer than two previous admissions, voluntary admission and regular discharge were more likely to be referred to high-intensity aftercare (psychiatric day clinic, inpatient rehabilitation). The readmission rate after one year did not differ between the different settings of aftercare (range 40.4–42.9%). CONCLUSIONS: The findings of this study suggest that patients suffering from severe substance use disorders and/or from an unfavourable course of disease who would benefit from a more intensive aftercare setting, such as psychiatric day clinics or inpatient rehabilitation programs, might be under-treated, whereas patients with a rather favourable prognosis might similarly benefit from a less intensive treatment setting, such as psychiatric outpatient care. Regarding the comparable readmission rates, we recommend considering more efficient resource management by promoting stepped care approaches for substance use disorders and establishing standardised placement criteria in Switzerland.

Since the industrial revolution, the relationship between unemployment and psychiatric disorders has been a subject of high interest. Currently, regarding the correlation between unemployment and substance-use disorders (SUDs), only older, often isolated and fragmented research results are available in the literature. This review was based on an extensive literature search of the European and North American literature in most relevant databases for “unemployment” and “substance use” related to “drugs”, “alcohol”, “nicotine”, and “tobacco” between November 2022 and January 2023, according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) guidelines. A total of 59,117 papers were identified, of which only 33 articles were identified as relevant to the research objective. The literature showed significantly higher prevalence rates of SUDs involving divergent psychotropic substances among unemployed people. Unemployment was found to be a risk factor for SUD, and vice versa. However, the correlation between unemployment and relapses or smoking cessation was inconsistent. In addition, there appeared to be a mild effect of business cycles on SUD. The results showed significant multifaceted correlations between unemployment and SUD, indicating that prevention and early intervention are required to prevent harmful psychosocial consequences, such as social disintegration and severe psychiatric disorders.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Abstract Background Alzheimer’s disease (AD) is a neurodegenerative disorder associated with extracellular amyloid-β peptide deposition and progressive neuron loss. Strong evidence supports that neuroinflammatory changes such as the activation of astrocytes and microglia cells are important in the disease process. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that has recently been associated with an emerging role in neuroinflammation, which has been reported to be increased in post-mortem brain samples from AD and Parkinson’s disease patients. Methods The present study describes the partial “fit for purpose” validation of a commercially available immunoassay for the determination of GPNMB levels in the cerebrospinal fluid (CSF). We further assessed the applicability of GPNMB as a potential biomarker for AD in two different cohorts that were defined by biomarker-supported clinical diagnosis or by neuroimaging with amyloid positron emission tomography, respectively. Results The results indicated that CSF GPNMB levels could not distinguish between AD or controls with other neurological diseases but correlated with other parameters such as aging and CSF pTau levels. Conclusions The findings of this study do not support GPNMB in CSF as a valuable neurochemical diagnostic biomarker of AD but warrant further studies employing healthy control individuals.

IntroductionOver the last decade, the use of New/Novel Synthetic Opioids (NSO) has emerged as an increasing problem, and especially so in the USA. However, only little is known about the prevalence and history of NSO use in European heroin dependents.MethodA cross-sectional multicenter study, carried out with the means of both standardized interviews and urine toxicology enhanced screening, in a sample of opioid addicted patients referred for an in-patient detoxification treatment.ResultsSample size included here n = 256 patients; prior to admission, 63.7% were prescribed with an opioid maintenance treatment. Lifetime use of heroin and opioid analgesics was reported by 99.2 and 30.4%, respectively. Lifetime NSO/fentanyl use was reported by 8.7% (n = 22); a regular use was reported by 1.6% (n = 4), and ingestion over the 30 days prior to admission by 0.8% (n = 2). Most typically, patients had started with a regular consumption of heroin, followed by maintenance opioids; opioid analgesics; and by NSO. Self-reported data were corroborated by the toxicology screenings carried out; no evidence was here identified for the presence of heroin being contaminated by fentanyl/derivatives.DiscussionNSO and also opioid analgesics did not play a relevant role in the development and the course of opioid/opioid use disorders in German patients referred for an inpatient detoxification treatment.

BackgroundThe prevalence of cannabis use and cannabis use disorders (CUD) has significantly increased over time. However, there are no approved pharmacological treatments for CUD. The aim of this study was to determine the efficacy and safety of various medical cannabinoids in the treatment of CUD.MethodsWe conducted a systematic review of randomized controlled trials which evaluated the therapeutic potential of medical cannabinoids in individuals with CUD and summarized the main study outcomes in terms of cannabis use, abstinence, withdrawal symptoms, craving, retention in treatment and adverse events.ResultsWe identified eight trials with a total of 667 study participants. Dronabinol reduced cannabis withdrawal symptoms whereas nabiximols, cannabidiol and PF-04457845, a fatty acid amide inhibitor, also reduced cannabis use and improved abstinence, compared to placebo. Nabilone failed to demonstrate efficacy in the treatment of CUD. All medications were well-tolerated.ConclusionsCannabinoid receptor agonists, i.e., dronabinol and nabilone, showed only limited or no therapeutic potential in the treatment of CUD. In contrast, modulators of endocannabinoid activity, i.e., nabiximols, cannabidiol and PF-04457845, demonstrated broader efficacy which covered almost all aspects of CUD. Endocannabinoid modulation appears to be a promising treatment approach in CUD, but the evidence to support this strategy is still small and future research in this direction is needed.

Invariant NK T (iNKT) cells are implicated in viral clearance; however, their role in hepatitis C virus (HCV) infection remains controversial. Here, iNKT cells were studied during different stages of HCV infection. iNKT cells from patients with acute HCV infection and people who inject drugs (PWID) with chronic or spontaneously resolved HCV infection were characterized by flow cytometry. In a longitudinal analysis during acute HCV infection, frequencies of activated CD38+ iNKT cells reproducibly declined in spontaneously resolving patients, whereas they were persistently elevated in patients progressing to chronic infection. During the first year of infection, the frequency of activated CD38+ or CD69+ iNKT cells strongly correlated with alanine transaminase levels with particularly pronounced correlations in spontaneously resolving patients. Increased frequencies of activated iNKT cells in chronic HCV infection were confirmed in cross-sectional analyses of PWID with chronic or spontaneously resolved HCV infection; however, no apparent functional differences were observed with various stimulation protocols. Our data suggest that iNKT cells are activated during acute hepatitis C and that activation is sustained in chronic infection. The correlation between the frequency of activated iNKT cells and alanine transaminase may point toward a role of iNKT cells in liver damage.

Abstract Background Opioid Maintenance Treatment (OMT) is a well-evaluated treatment of opioid use disorder (OUD). Especially, under the condition of imprisonment, OMT is a preventive measure regarding infectious diseases such as hepatitis C. However, only a minority of prisoners with OUD are currently in OMT in numerous countries. In 2009, the Ministry of Justice of the federal state of North Rhine-Westphalia (NRW), Germany, launched the process of implementing OMT in prisons with various elements (e.g. development of recommendations regarding the treatment of prisoners with OUD, monitoring the number of prisoners in OMT, education of prison doctors). In the recommendations OMT was defined as the gold standard of treatment of OUD. Methods To assess the effectiveness of the implementation strategy a survey on the prevalence of OMT in prisons in NRW was carried out twice a year by the Ministry of Justice between 2008 and 2016. Participants were prisoners in NRW, Germany. The diagnosis of OUD at admission to prison and the treatment state on survey dates was measured. Results The number of prisoners in NRW dropped from 17,301 in 2008 to 16,432 in 2016. In the same period, the number of prisoners with OUD (mainly males) dropped from 4201 persons to 3650 persons and the number of prisoners in OMT increased from 139 persons (3.3%) to 1415 (38.7%) persons. Discussion Currently, the percentage of prisoners with OUD in OMT in NRW is almost reaching the treatment rate outside prisons in Germany (45–50%). However, after release from prison there is still a high risk for a discontinuation of OMT. Conclusions Overall, the top-down approach of implementing OMT in prisons in the federal state of NRW was effective.

Abstract Background Opioid Use Disorder (OUD) is a substance use disorder with a chronic course associated with comorbid mental and somatic disorders, a high burden of psychosocial problems and opioid maintenance treatment (OMT) as a standard treatment. In the US, OUD imposes a significant economic burden on society, with annual societal costs estimated at over 55 billion dollars. Surprisingly, in Europe and especially in Germany, there is currently no detailed information on the healthcare costs of patients with OUD. The goal of the present research is to gather cost information about OUD patients in OMT with a focus on maintenance medication and relapses. Methods We analysed health claims data of four million persons covered by statutory health insurance in Germany, applying a cost-of-illness approach and aimed at examining the direct costs of OMT patients in Germany. Patients with an ICD-10 code F11.2 and at least one claim of an OMT medication were stratified into the treatment groups buprenorphine, methadone or levomethadone, based on the first prescription in each of the follow-up years. Costs were stratified for years with and without relapses. Group comparisons were performed with ANOVA. Results We analysed 3165 patient years, the total annual sickness funds costs were on average 7470 € per year and patient. Comparing costs of levomethadone (8400 €, SD: 11,080 €), methadone (7090 €, SD: 10,900 €) and buprenorphine (6670 €, SD: 7430 €) revealed significant lower costs of buprenorphine compared to levomethadone (p

Background: In response to the COVID-19-pandemic, a lockdown was established in the middle of March 2020 by the German Federal Government resulting in drastic reduction of private and professional traveling in and out of Germany with a reduction of social contacts in public areas.Research Questions: We seek evidence on whether the lockdown has led to a reduced availability of illegal drugs and whether subjects with substance-related problems tried to cope with possible drug availability issues by increasingly obtaining drugs via the internet, replacing their preferred illegal drug with novel psychoactive substances, including new synthetic opioids (NSO), and/or by seeking drug treatment.Methods: A questionnaire was anonymously filled in by subjects with substance-related disorders, typically attending low-threshold settings, drug consumption facilities, and inpatient detoxification wards from a range of locations in the Western part of Germany. Participants had to both identify their main drug of abuse and to answer questions regarding its availability, price, quality, and routes of acquisition.Results: Data were obtained from 362 participants. The most frequent main substances of abuse were cannabis (n = 109), heroin (n = 103), and cocaine (n = 75). A minority of participants reported decreased availability (8.4%), increased price (14.4%), or decreased quality (28.3%) of their main drug. About 81% reported no change in their drug consumption due to the COVID-19 pandemic and the lockdown. A shift to the use of novel psychoactive substances including NSO were reported only by single subjects. Only 1–2% of the participants obtained their main drug via the web.Discussion: Present findings may suggest that recent pandemic-related imposed restrictions may have not been able to substantially influence either acquisition or consumption of drugs within the context of polydrug users (including opiates) attending a range of addiction services in Germany.

Background: Non-medical use (NMU) of prescription GABA analogs (pregabalin and gabapentin) has been reported especially in opiate dependent persons. However, by now the prevalence of NMU of gabapentinoids in the general population has not been sufficiently evaluated. The aim of this research paper is to determine the prevalence of prescription GABA analog NMU and associated demographics in five European countries with special detail of Spain.Methods: The RADARS Survey of Non-Medical Use of Prescription Drugs Program (NMURx) is a harmonized series of contemporaneous cross-sectional surveys of adults conducted in multiple countries. NMURx collects data from the general population in each participating country about NMU of prescription drugs, illicit drugs, and associated demographics. NMU was defined as “using a medication without a doctor's prescription or for any reason other than what was recommended by their doctor.” Responses from Spain (4Q2017, n=10,062) were analyzed in detail. Comparative data were available from France, Germany, Italy, and UK. Responses were collected using non-probability quota sampling and post-stratification population weighting was applied to reflect the national distributions of adults, based on age, gender, and census region. Rates of NMU and associated demographics were reported as rate of past 90-day NMU per 100,000 adult population with 95% confidence intervals.Results: Germany (1,197 per 100,000 adult population [95% CI: 1,004.3–1,379.1]) and United Kingdom (1,067 per 100,000 adult population [95% CI: 851.3–1,283.2]) presented the highest prevalence of gabapentinoids NMU. In Spain the prevalence of past 90 days GABA analog NMU was: 344.4, 95% (CI 204.8–484.0), with male predominance. Those who non-medically use GABA analogs had a higher prevalence of lifetime chronic pain, lifetime illicit drug use, and previous substance abuse treatment. In Spain, 20% of respondents who ever have used gabapentinoids, reported a lifetime NMU; the prevalence was higher for pregabalin 624 (6.2%) than for gabapentin 444 (4.4%). The main reasons for use were to self-treat pain and other medical conditions.Conclusions: The risk of NMU of gabapentinoids should not be neglected. Subjects with a history of chronic pain and lifetime substance use disorders had an increased risk of NMU of gabapentinoids.

Abstract Background Knowledge of health-related quality of life (HRQOL) of patients receiving opioid substitution treatment (OST) is limited and fragmented. The present study examines the HRQOL of a large national sample of OST patients in Germany and sociodemographic and clinical correlates. Methods Cross-sectional data on the HRQOL of 2176 OST patients was compared with German general population norms. Patients were recruited from 63 OST practices across Germany. To identify correlates of HRQOL, as measured with the SF-12, we performed bi- and multivariate analyses with sociodemographic and clinical variables, including patient- and clinician-reported outcomes on physical and mental health. Results Patients’ HRQOL was significantly poorer than in the general population, especially their mental HRQOL. Factors associated with lower physical HRQOL were older age, longer duration of opioid dependence, hepatitis C virus infection, and HIV infection. Benzodiazepine use was associated with lower mental HRQOL, and amphetamine use with higher physical HRQOL, compared to non-use of these substances. For both mental and physical HRQOL, the factor with the strongest positive association was employment and the factors with the strongest negative associations were physical and mental health symptom severity, psychiatric diagnosis, and psychopharmacological medication. Conclusions Compared to the general population, we found substantially lower HRQOL in OST patients, especially in their mental HRQOL. OST programs can benefit from further improvement, particularly with regard to mental health services, in order to better serve their patients’ needs. Clinicians may consider the use of patient-reported outcome measures to identify patients’ subjective physical and psychological needs. Further research is needed to determine if employment is a cause or consequence of improved HRQOL. Trial registration ClinicalTrials.gov: NCT02395198, retrospectively registered 16/03/2015

[This corrects the article DOI: 10.1371/journal.pone.0236268.].

Background: For cannabis-dependent subjects, the relationship between cannabis withdrawal syndrome (CWS) severity and the urine cannabinoid concentrations are unclear; we investigated this using a commercial point-of-care (POC) enzyme immunoassay detecting 11-nor-9-carboxy-Delta-9-tetrahydrocannabinol (THC-COOH).Methods: Observational study of 78 adult chronic cannabis-dependent subjects assessed over a 24-day inpatient detoxification treatment, with 13 serial measurement days. Repeated Measures Correlation and Multilevel Linear Models were employed.Results: Absolute urinary THC-COOH levels significantly correlated with Marijuana Withdrawal Checklist (MWC) scores across the entire study duration (r = 0.248; p < 0.001). Correlation between serial creatinine-adjusted THC-COOH ratios and serial MWC scores emerged as significant only in the sample with higher MWC scores (>11 points) at admission (n = 21; r = 0.247; p = 0.002). The aforementioned significant relationships have persisted when replacing the absolute THC-COOH-levels with the (relative) day-to-day change in urinary THC-COOH levels. MWC scores were significantly correlated with the Clinical Global Impression-Severity (CGI-S; r = 0.812; p < 0.001). Females showed a significantly slower decline in urine THC-COOH levels and prolonged CWS course characterized by substantial illness severity (per CGI-S), occurring in nearly 30% of cases.Conclusion: Urine cannabinoid levels (THC-COOH) determined by POC assay significantly predicted CWS severity (moderate correlation), guiding detoxification treatment duration. In patients with MWC > 11 points upon admission, creatinine-adjusted THC-COOH ratios also significantly predicted CWS severity—again with moderate effect size. Females showed prolonged urinary THC-COOH elimination and cannabis withdrawal.

Background: Chemsex is defined as using certain substances immediately before or during sexual activities to facilitate, prolong and/or intensify sexual experience, mainly by some communities of men who have sex with men (MSM). Four substances are typically associated with chemsex: methamphetamine, mephedrone, GHB/GBL, and ketamine. While there is a lot of evidence for increased prevalence of HIV, sexually transmitted infections and other sexual health measures among MSM, who engage in chemsex, there has been little research on mental health aspects. This study aims to describe aspects of mental health among a sample of German men who have sex with men (MSM) who engage in chemsex and to describe potentially adverse consequences of chemsex behavior.Method: This paper refers to a subset of participants from the German Chemsex Survey, an MSM-community recruited, self-completed online survey with a self-selected convenience sample. The survey comprised 420 different items considering recreational substance use, substance use in sexual settings, mental health, sexual transmitted infections, adverse consequences of chemsex behavior, and experiences of non-consensual sex acts. A group of participants who used methamphetamine, mephedrone, GHB/GBL, and/or ketamine in a sexual setting in the last 12 months (n = 280, chemsex group) was analyzed regarding symptoms of depression (PHQ-9), general anxiety disorder (GAD-7), somatization (PHQ-15), and PTSD (Primary Care PTSD Screen). Group comparisons were conducted between the chemsex group and men who did not use substances in a sexual context (n = 177, non-chemsex group). Mean scores of mental health measures were compared, as well as scores above a cut-off that indicates clinically relevant symptoms. Logistical regression was utilized to determine whether mental health measures can predict adverse consequences of engagement in chemsex behaviors.Results: A total of 1,583 men started the survey; 1,050 participants provided information on substance use. Twenty-seven percent of participants (n = 280) reported that they used methamphetamine, mephedrone, GHB/GBL and/or ketamine in a sexual setting in the last 12 months. The chemsex group showed significantly higher mean scores for depression, anxiety, and somatization than the non-chemsex group, but effect sizes were low. Even though mean scores were heightened, they were still far below the cut-off for clinically relevant symptoms. The chemsex group reported significantly higher incidences of non-consensual sex acts compared with the non-chemsex group. Some men in the chemsex-group experienced potentially adverse consequences, such as loss of control regarding time and money spent for chemsex activities or amount of substances used at one occasion (49.6%), negative impacts on social functioning (33.6%), psychotic symptoms (13.2%), and physically aggressive behavior toward others (2.9%). Clinically relevant symptoms did not predict a higher likelihood for adverse consequences.Discussion: Mean scores for depression, anxiety, and somatization were significantly higher in the chemsex-group, but effect sizes were low. Both groups reported poorer mental health compared to men in the German general population. Mental health measures did not contribute to predict potentially adverse consequences of chemsex behavior.

Background: Over the past 15 years, comparative assessments of psychoactive substance harms to both users and others have been compiled by addiction experts. None of these rankings however have included synthetic cannabinoids or non-opioid prescription analgesics (NOAs, e.g., gabapentinoids) despite evidence of increasing recreational use. We present here an updated assessment by German addiction medicine experts, considering changing Western consumption trends–including those of NOAs.Methods: In an initial survey, 101 German addiction medicine physicians evaluated both physical and psychosocial harms (in 5 dimensions) of 33 psychoactive substances including opioids and NOAs, to both users and others. In a second survey, 36 addiction medicine physicians estimated the relative weight of each health and social harm dimension to determine the overall harm rank of an individual substance. We compared our ranking with the most recent European assessment from 2014.Results: Illicit drugs such as methamphetamine, heroin, cocaine and also alcohol were judged particularly harmful, and new psychoactive drugs (cathinones, synthetic cannabinoids) were ranked among the most harmful substances. Cannabis was ranked in the midrange, on par with benzodiazepines and ketamine—somewhat more favorable compared to the last European survey. Prescribed drugs including opioids (in contrast to the USA, Canada, and Australia) were judged less harmful. NOAs were at the bottom end of the ranking.Conclusion: In Germany, alcohol and illicit drugs (including new psychoactive substances) continue to rank among the most harmful addictive substances in contrast to prescribed agents including opioid analgesics and NOAs. Current laws are incongruent with these harm rankings. This study is the first of its kind to include comparative harm rankings of several novel abused substances, both licit/prescribed and illicit.

BackgroundAbout 15 years ago, a diverse group of new recreational psychotropic substances began to emerge, which were marketed for example as “legal highs,” “research chemicals,” or “designer drugs.” These substances were later subsumed under the label “Novel Psychoactive Substances” (NPS). Important NPS classes are cathinones, synthetic cannabimimetics, phenethylamines, and herbal drugs. The health care system for psychotropic substance use disorders (SUDs) traditionally focused on a few substances, such as alcohol, heroin, cocaine, amphetamines, or cannabis. Users of illicit substances often engage in polydrug use. However little is known about the prevalence of NPS use within the group of “classical” illicit substance users.ObjectiveWe investigated lifetime and recent use of NPS and other drugs in patients who underwent in-patient detoxification treatment from illicit drugs in Germany.MethodsIn a multicenter study with eight participating facilities, patients admitted to treatment underwent a standardized interview at admission, concerning their past and current substance use. The interview comprised classical substances of abuse, NPS, and rarely used substances such as LSD. In addition, participating sites had the opportunity to analyze their patients’ routine drug screenings by means of gas chromatography/mass spectrometry (GC/MS), which permitted detection of NPS.ResultsInterviews from 295 patients could be analyzed. Most patients were opiate dependent and multiple substance users. About 32% reported use of synthetic cannabimimetics during lifetime, but usually only a few times. An important reason for their use was that NPS were not detected by drug testing in prisons or drug treatment facilities. Cathinones, herbal drugs or other NPS had rarely been used during lifetime. NPS use during the last 30 days before admission was nearly zero. This was confirmed by urine analysis results. In contrast, lifetime and current use of opiates, alcohol, cocaine, benzodiazepines, and cannabis was high. In addition, 18% reported of regular unprescribed pregabalin use during lifetime, and 20% had recently used pregabalin.ConclusionPatients admitted to drug detoxification treatment showed multiple substance use, but this did not include NPS use. The diversion of legal medications such as pregabalin in this group is a serious concern.

Background and aimsData on rates of prescription opioid use disorder (pOUD) in European countries is limited. The aim of this investigation was to analyze a representative population sample regarding the 1-year prevalence of opioid use disorder in patients who received prescription opioid pain therapy and to identify related risk factors.DesignCross-sectional secondary data analysis.SettingSecondary data analysis based on data from the 2015 Epidemiological Survey of Substance Abuse (ESA 2015) in Germany.ParticipantsGerman-speaking individuals living in private households aged 18 to 64 years were investigated. A total of 9204 individuals participated in the survey, resulting in a response rate of 52.2%.Primary and secondary outcome measuresPrimary outcome measure was the weighted prevalence of pOUD in the subgroup of study participants who had received prescription opioids. Secondary outcome measure was an analysis of risk factors connected with pOUD in the same subgroup.FindingsA total of n = 9204 participants were included in the study of which n = 275 had received an opioid prescription in the last 12 months of which n = 54 were diagnosed with pOUD. The weighted 1-year prevalence of pOUD was 21.2% (mild: 14.7% | moderate: 3.5% | severe: 2.9%). Participants who had received opioid pain therapy had significantly higher odds of pOUD if they reported signs of depression (OR: 2.69; CI 95%: 1.13-6.38), inexplicable physical complaints (OR: 2.68; CI 95%: 1.14-6.31) or a psychiatric diagnosis (OR: 4.12; CI 95%: 1.36-12.43), and significantly lower odds of pOUD if they reported the use of non-opioid painkillers (OR: 0.27; CI 95%: 0.09-0.81).ConclusionspOUD is a common phenomenon in working-age patients who receive prescription opioid pain therapy in Germany and may be related to the co-existence of psychosomatic and psychiatric disorders such as depression.

Background: Co-occurring posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are associated with a more severe course and worse outcome than either disorder alone. In Europe, few treatments have been evaluated for PTSD and SUD. Seeking Safety, a manualized, integrated, cognitive-behavioural treatment, has been shown to be effective in studies in the USA. Objective: To test the efficacy of Seeking Safety plus treatment as usual (TAU) in female outpatients with PTSD and SUD compared to Relapse Prevention Training (RPT) plus TAU and TAU alone. Method: In five German study centres a total of N = 343 women were randomized into one of the three study conditions. PTSD severity (primary outcome), substance use, depression and emotion dysregulation (secondary outcomes) were assessed at baseline, post-treatment, as well as at three months and six months post-treatment. Results: Treatment participants attended M = 6.6 sessions (Seeking Safety) and M = 6.1 sessions (RPT). In an intent-to-treat analysis, Seeking Safety plus TAU, RPT plus TAU and TAU alone showed comparable decreases in PTSD severity over the course of the study. Seeking Safety plus TAU showed superior efficacy to TAU alone on depression and emotion regulation and RPT plus TAU was more effective than TAU alone on number of substance-free days and alcohol severity. Minimum-dose analyses suggest additional effects of both programmes among participants who attended at least eight group sessions. Conclusions: With respect to PTSD symptoms, a brief dose of Seeking Safety and RPT in addition to TAU was not superior to TAU alone in women with PTSD and SUD. However, Seeking Safety and RPT showed greater reductions than TAU alone in other domains of psychopathology and substance use outcomes respectively. Future studies should investigate further variables, such as what aspects of each treatment appeal to particular patients and how best to disseminate them.

Introduction: Men who have sex with men (MSM) are a vulnerable subgroup for problems with substance use, including crystal methamphetamine. Drug use in sexual settings, commonly referred to as “chemsex,” has been an issue of growing concern in MSM communities. Recreational drugs commonly associated with chemsex include crystal methamphetamine, gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL), mephedrone, and ketamine. Drug use in sexual settings is correlated with sexual practices associated with the acquisition and transmission of sexually transmitted infections, including HIV and hepatitis C. Adverse mental health outcomes are often reported at higher rates among MSM who use methamphetamine.Methods: This paper refers to a subset of participants from the German Chemsex Survey, an MSM-community recruited, self-completed online survey with a self-selected convenience sample. Participants who used crystal methamphetamine for sex (n = 130) were compared to participants who did not use drugs for sex (n = 177). The survey comprised 420 different items considering recreational substance use, substance use in sexual settings, harm reduction strategies, mental health, sexual transmitted infections, and mental health care service utilization.Results: A total of 1,583 men started the survey; 1,050 participants provided information on substance use. Twenty-seven percent of participants used crystal methamphetamine in the last 12 months, and of those, 89% used methamphetamine in a sexual setting and 50% reported injecting methamphetamine. Regarding mental health, participants who reported methamphetamine use in sexual settings were more likely to report symptoms of depression, somatization, anxiety, and posttraumatic stress disorder (PTSD) than the German male general population. Participants who reported methamphetamine use for sex were more likely to report symptoms of major depression, being HIV positive, and taking HIV pre-exposure prophylaxis (PrEP) than participants who did not report methamphetamine use. Most participants used harm reduction practices to reduce the risks associated with using methamphetamine in sexual settings.Conclusion: Crystal methamphetamine is used in the context of sexual activities by German MSM. Poorer mental health status than in the male general population was observed. MSM who used methamphetamine in this study seemed to be aware of potential health risks associated with their substance use and utilized harm reduction strategies and biomedical HIV prevention strategies like PrEP.

Abstract Objective The cognitive capacity to change perspective is referred to as theory of mind (ToM). ToM deficits are detectable in a variety of psychiatric and neurological disorders. Since executive abilities are closely associated with ToM skills, we suspected that due to a common neuropsychological basis, ToM deficits exist in treatment‐naïve adults with attention‐deficit/hyperactivity disorder (ADHD). Methods Performance of treatment‐naïve adults with ADHD (N = 30) in tasks assessing executive functions (Trail Making Test, Stroop color–word test, and Test Battery for Attentional Performance), empathy skills (Cambridge Behaviour Scale), and ToM (Movie for Assessment of Social Cognition) was compared with that of a healthy control group (N = 30) matched according to basic demographic variables. Results Compared to healthy controls, treatment‐naïve adults with ADHD showed deficits in various executive functions and the ability to empathize (all p

The restrictive measures adopted during the COVID-19 pandemic modified some previously consolidated drug use patterns. A focus on social networks allowed drug users to discuss, share opinions and provide advice during a worldwide emergency context. In order to explore COVID-19-related implications on drug trends/behaviour and on most popular psychotropic substances debated, the focus here was on the constantly updated, very popular, Reddit social platform’s posts and comments. A quantitative and qualitative analysis of r/Drugs and related subreddits, using a social media listening netnographic approach, was carried out. The post/comments analysed covered the time-frame December 2019–May 2020. Between December 2019 and May 2020, the number of whole r/Drugs subreddit members increased from 619,563 to 676,581 members, respectively, thus increasing by 9.2% by the end of the data collection. Both the top-level r/Drugs subreddit and 92 related subreddits were quantitatively analysed, with posts/comments related to 12 drug categories. The drugs most frequently commented on included cannabinoids, psychedelics, opiates/opioids, alcohol, stimulants and prescribed medications. The qualitative analysis was carried out focussing on four subreddits, relating to some 1685 posts and 3263 comments. Four main themes of discussion (e.g., lockdown-associated immunity and drug intake issues; drug-related behaviour/after-quarantine plans’ issues; lockdown-related psychopathological issues; and peer-to-peer advice at the time of COVID-19) and four categories of Redditors (e.g., those continuing the use of drugs despite the pandemic; the “couch epidemiologists”; the conspirationists/pseudo-science influencers; and the recovery-focused users) were tentatively identified here. A mixed-methods, social network-based analysis provided a range of valuable information on Redditors’ drug use/behaviour during the first phase of the COVID-19 pandemic. Further studies should be carried out focusing on other social networks as well as later phases of the pandemic.

Designer benzodiazepines (DBZDs) represent a serious health concern and are increasingly reported in polydrug consumption-related fatalities. When new DBZDs are identified, very limited information is available on their pharmacodynamics. Here, computational models (i.e., quantitative structure-activity relationship/QSAR and Molecular Docking) were used to analyse DBZDs identified online by an automated web crawler (NPSfinder®) and to predict their possible activity/affinity on the gamma-aminobutyric acid A receptors (GABA-ARs). The computational software MOE was used to calculate 2D QSAR models, perform docking studies on crystallised GABA-A receptors (6HUO, 6HUP) and generate pharmacophore queries from the docking conformational results. 101 DBZDs were identified online by NPSfinder®. The validated QSAR model predicted high biological activity values for 41% of these DBDZs. These predictions were supported by the docking studies (good binding affinity) and the pharmacophore modelling confirmed the importance of the presence and location of hydrophobic and polar functions identified by QSAR. This study confirms once again the importance of web-based analysis in the assessment of drug scenarios (DBZDs), and how computational models could be used to acquire fast and reliable information on biological activity for index novel DBZDs, as preliminary data for further investigations.

Emotional lability is a common problem in adult patients with ADHD and is usually treated with methylphenidate. It is generally known that music can be used to improve mood in healthy adults. Therefore, this study was conducted to test the suitability of music as a possible non-pharmacological measure to improve mood. Forty patients with ADHD and 44 healthy control subjects were randomly assigned to one of two experimental conditions. The first group (music group) listened to Mozart’s music (KV 448) for 10 min while the second group remained in a silent room for 10 min (silence group). Subjective arousal and mood were assessed using self-report questionnaires before and after each condition. We showed that music listening led to a decrease in negative mood (sadness and hopelessness) in the ADHD group as well as in healthy controls. This effect was not evident in both silence groups.

We investigated the MMN at electrode Fz to 12% temporally predictable or unpredictable duration decrement deviant stimuli in 29 healthy controls and 31 schizophrenia patients. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4 s while it varied randomly in the unpredictable condition.Here we report detailed data tables and multivariate analysis of variance results (MANOVA) on MMN, P3a and standard ERP data including details on follow-up analyses. An extended figure shows MMN difference curves and averages to standard and deviant stimuli in both experimental conditions and subject groups. Keywords: Cognitive Neuroscience, Neurophysiology, Mismatch Negativity

Background: Substance use disorders (SUD) belong to the most frequent behavioural consequences of childhood abuse and neglect (CAN). If parents are concerned, SUD are also an important risk factor for CAN. The relationship between CAN and SUD remains poorly understood. There is a need of adequate treatments for SUD patients suffering from the consequences of CAN, as well as for approaches to prevent CAN by parents with SUD. Objective: To describe the aims and the structure of a German research network on relationships between CAN and SUD (CANSAS network). Method: Descriptive overview of the aims, and the different project clusters of the network. Results: The aims of the CANSAS network are: (1) to examine relationships between SUD and CAN; (2) to examine the effects of an evidence-based treatment for SUD patients with posttraumatic disorders; and (3) to provide SUD services with tools to diagnose CAN, and to assess the risk of maltreatment among parents with SUD. The aims of the network are addressed by six projects in three different project clusters (mediators and risk factors, evidence-based treatment, and improvement of services). Conclusions: It is expected that the CANSAS network will advance the understanding of relationships between early adversity and substance use disorders. It will bring forward the discussion about promising treatments for SUD patients with experiences of CAN. Finally it will provide services with measures to identify patients with CAN, and with tools to break the trans-generational cycle of adversity.

INTRODUCTION: Comorbid substance related disorders are a major health problem for patients in opioid maintenance treatment (OMT). It was investigated whether a reinforcement scheme adapted to the regulatory and financial restrictions of routine treatment reduces concomitant drug use. METHODS: OMT patients from 7 clinics who were using cocaine, benzodiazepines, heroin or amphetamines were randomly allocated to either treatment as usual (n = 64) or treatment with an additional escalating reinforcement scheme (n = 72) in which a patient's number of weekly take-home dosages was increased after 1, 4, 8 and 12 consecutive weeks with drug-free urine specimens. Trial duration was 26 weeks. RESULTS: Completion rates were 64% for controls and 62.5% in the experimental group. Mean number of drug-free weeks was 11.3 (SD 8.5) for the control group and 9.8 (8.9) for the experimental group (p = 0.30). CONCLUSION: The intervention was not effective compared to routine treatment. Additional features might be necessary to achieve an effect, e.g. a higher frequency of urine sampling or use of other reinforcers. It has to be further investigated how interventions which have been proven effective in experimental studies can successfully be adapted to routine care conditions.

Alterations in reward and punishment processing have been reported in adults suffering from long-term cannabis use. However, previous findings regarding the chronic effects of cannabis on reward and punishment processing have been inconsistent. In the present study, we used functional magnetic resonance imaging (fMRI) to reveal the neural correlates of reward and punishment processing in long-term cannabis users (n = 15) and in healthy control subjects (n = 15) with no history of drug abuse. For this purpose, we used the well-established Monetary Incentive Delay (MID) task, a reliable experimental paradigm that allows the differentiation between anticipatory and consummatory aspects of reward and punishment processing. Regarding the gain anticipation period, no significant group differences were observed. In the left caudate and the left inferior frontal gyrus, cannabis users were - in contrast to healthy controls - not able to differentiate between the conditions feedback of reward and control. In addition, cannabis users showed stronger activations in the left caudate and the bilateral inferior frontal gyrus following feedback of no punishment as compared to healthy controls. We interpreted these deficits in dorsal striatal functioning as altered stimulus-reward or action-contingent learning in cannabis users. In addition, the enhanced lateral prefrontal activation in cannabis users that is related to non-punishing feedback may reflect a deficit in emotion regulation or cognitive reappraisal in these subjects.

Altered time reproduction is exhibited by patients with adult attention deficit hyperactivity disorder (ADHD). It remains unclear whether memory capacity influences the ability of adults with ADHD to reproduce time intervals.We conducted a behavioral study on 30 ADHD patients who were medicated with methylphenidate, 29 unmedicated adult ADHD patients and 32 healthy controls (HCs). We assessed time reproduction using six time intervals (1 s, 4 s, 6 s, 10 s, 24 s and 60 s) and assessed memory performance using the Wechsler memory scale.The patients with ADHD exhibited lower memory performance scores than the HCs. No significant differences in the raw scores for any of the time intervals (p > .05), with the exception of the variability at the short time intervals (1 s, 4 s and 6 s) (p < .01), were found between the groups. The overall analyses failed to reveal any significant correlations between time reproduction at any of the time intervals examined in the time reproduction task and working memory performance (p > .05).We detected no findings indicating that working memory might influence time reproduction in adult patients with ADHD. Therefore, further studies concerning time reproduction and memory capacity among adult patients with ADHD must be performed to verify and replicate the present findings.

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10−6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

Currently, a major clinical challenge is to distinguish between chronic liver disease caused by metabolic syndrome (non-alcoholic fatty liver disease, NAFLD) from that caused by long term or excessive alcohol consumption (ALD). The etiology of severe liver disease affects treatment options and priorities for liver transplantation and organ allocation. Thus we compared physiologically similar NAFLD and ALD patients to detect biochemical differences for improved separation of these mechanistically overlapping etiologies.In a cohort of 31 NAFLD patients with BMI below 30 and a cohort of ALD patient with (ALDC n = 51) or without cirrhosis (ALDNC n = 51) serum transaminases, cell death markers and (adipo-)cytokines were assessed. Groups were compared with One-way ANOVA and Tukey's correction. Predictive models were built by machine learning techniques.NAFLD, ALDNC or ALDC patients did not differ in demographic parameters. The ratio of alanine aminotransferase/aspartate aminotransferase--common serum parameters for liver damage--was significantly higher in the NAFLD group compared to both ALD groups (each p

Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood.50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed.IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients.Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders.