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Introduction: Human studies about the impact of cannabis use on both healthy kidneys as well as kidney function in patients with kidney disease are lacking. To shed more light on this understudied ...

Studies for repurposed drugs in severe acute respiratory syndrome coronavirus type 2-infected and coronavirus disease 2019 (COVID-19) patients are ongoing. According to preclinical research, antidepressants (ADs) might be useful in the treatment of COVID-19.We conducted a scoping review including clinical studies on AD effects on SARS-CoV-2 infection and COVID-19.As of January 2, 2022, we found 14 clinical studies, which could be included into this review. Among them, there were 2 randomized, placebo-controlled studies and 2 prospective parallel-group studies about the efficacy/effectiveness and tolerability of fluvoxamine. The remaining studies were mainly retrospective studies considering COVID-19 hospital populations predominantly exposed to fluoxetine (N = 3), other selective serotonin reuptake inhibitors (SSRI), selective norepinephrine reuptake inhibitors (SNRI), and trazodone. The vast majority were hospital studies and assessed COVID-19 severity (morbidity) and mortality as primary endpoints. The only outpatient study (fluvoxamine) investigated the COVID-19-related hospitalization rate, and 1 psychiatric hospital study (SSRI, SNRI, trazodone) focused on the SARS-CoV-2 infection rate.At present, the best evidence of an "anti-COVID-19" potential of ADs exists for fluvoxamine and, to a lesser extent, for fluoxetine. Preliminary evidence had found that patients exposed to SSRI or SNRI substance classes might have a reduced mortality risk and that trazodone might reduce SARS-CoV-2 infection rates. Three studies found no relevant influence of ADs on COVID-19 morbidity and mortality, and 1 study described increased mortality. The latter study, however, did not differentiate between psychotropic medication and ADs. Tricyclics and monoamine oxidase inhibitors are still absolute "dark zones" in COVID-19 research. Further controlled studies testing the effectiveness/efficacy and tolerability/safety (as well as the treatment timing and duration) of different AD substance classes in COVID-19 and post/long-COVID patients of various populations are warranted.

To date, we cannot find any current international comparative study on the assessment of a benefit/harm profile of various licit and illicit psychoactive substances conducted by adult drug users and addiction experts as well. Particularly, there is no study from the German-speaking area of Western Europe.In addition to the data already published by 101 German addiction medicine experts (published in this journal, [1]), we carried out interviews using a structured questionnaire with 100 German substance dependent users, residing in acute and rehabilitation clinical setting, to evaluate 34 psychoactive substances regarding their health and social harm potential for users and others as well as their potential benefit.Both, users and experts estimated traditional illicit drugs, such as heroin, crack/cocaine and methamphetamine, to be particularly harmful. Synthetic cannabinoids, alcohol and benzodiazepines were in the upper midfield, cannabis and psychotropic mushrooms in the lower midfield, and gabapentinoids at the bottom of the harm rankings of both, users and experts. In comparison with the experts, the users estimated methadone and benzodiazepines to be significantly more harmful. In the benefit analysis, users rated traditional illicit drugs including cannabis and psychotropic mushrooms as well as nicotine as significantly more useful than the experts. In contrast to the experts (traditional illicit drugs), the users did not assess any substance as very harmful and very useless at the same time. Only a few users reported to have experiences with opioid analgesics which, however, did not differ between the users´ and experts´ harm/benefit-assessments. Neither users nor experts predicted cannabis-legalization to change the overall risk potential of cannabis. Specific cognitive valuation biases seemed to be prominent in both groups.This study presents first harm/benefit assessments of psychotropic substances from the perspective of German addiction medicine experts and drug users. The results can be valuable to the psychoeducation of substance-addicted individuals and to current restriction or legalization debates.Es existiert keine aktuelle internationale Vergleichsstudie von Drogenkonsumenten und Suchtexperten zur Einschätzung des Risiko/Nutzen-Profils legaler und illegaler psychotroper Substanzen und zudem keine auch ältere Studie dazu aus dem deutschsprachigen Raum.Ergänzend zu den bereits veröffentlichten Daten 101 deutscher Suchtexperten (in diesem Journal publiziert, [1]) wurden analog 100 substanzabhängige Drogenkonsumenten während ihrer stationären Entzugsbehandlung (Akutkrankenhaus) oder Entwöhnungsbehandlung (Rehabilitationskrankenhaus) per strukturiertem Fragebogen zu ihrer Einschätzung des Schadens- und Nutzenpotentials von 34 legalen und illegalen psychotroper Substanzen interviewt.In Übereinstimmung bewerteten Konsumenten und Experten, dass die traditionellen illegalen Drogen Heroin, Crack/Kokain und Methamphetamin das größte Schädlichkeitspotential besitzen. Synthetische Cannabinoide, Alkohol und Benzodiazepine befanden sich im oberen Mittelfeld, Cannabis und psychotrope Pilze im unteren Mittelfeld und Gabapentinoide am Ende der Gefährdungsrangordnung beider Gruppen. Methadon und Benzodiazepine wurden von Konsumenten signifikant gefährlicher eingestuft. Hinsichtlich des Substanznutzens bewerteten Konsumenten traditionelle illegale Drogen einschließlich Cannabis und psychotrope Pilze ebenso wie Nikotin als signifikant nützlicher als die Experten. Im Gegensatz zu den Experten bewerteten die Konsumenten keine Substanz als extrem gefährlich bei gleichzeitig geringer Nützlichkeit. Erfahrungen mit Opioid-Analgetika konnten nur von wenigen Konsumenten berichtet werden, wurden aber bezüglich ihres Risiko/Nutzen-Profils ähnlich den Expertenurteilen eingeordnet. Durch Legalisierung von Cannabis erwarten weder Konsumenten noch Experten eine Änderung des Gefährdungspotentials. In beiden Gruppen existierten spezifische kognitive Bewertungsverzerrungen.Die vorliegende Studie zeigt erste Informationen aus dem deutschsprachigen Raum zur Risiko/Nutzen-Bewertung psychotroper Substanzen aus der Perspektive von Suchtexperten und Konsumenten. Diese können als Beitrag für die Psychoedukationsarbeit in der Behandlung von Substanzabhängigen aber auch für aktuelle gesundheitspolitischen Debatten zur legalen Verfügbarkeit von Drogen zum Freizeitgebrauch hilfreich sein.

Introduction Several psychiatric and somatic medications are assumed to improve COVID-19-symptoms. These include antidepressants, antipsychotics, and anticonvulsants as well as anticoagulants, statins, and renin-angiotensin-aldosterone-system (RAAS)-inhibitors for somatic comorbid conditions. All these agents may reduce the hyperinflammatory response to SARS/CoV-2 or the related negative cardio-cerebrovascular outcomes. Methods In a retrospective longitudinal, multi-center inpatient study, we sought to explore the influence of psychiatric medications on COVID-19, comprising the period from diagnosing SARS/CoV-2-infection via PCR (nasopharyngeal swab) up to the next 21 days. Ninety-six psychiatric inpatients (mean age [SD] 65.5 (20.1), 54% females) were included. The primary outcome was the COVID-19-duration. Secondary outcomes included symptom severity and the presence of residual symptoms. Results COVID-19-related symptoms emerged in 60 (62.5%) patients, lasting 6.5 days on average. Six (6.3%) 56–95 years old patients died from or with COVID-19. COVID-19-duration and residual symptom-presence (n=22, 18%) were not significantly related to any substance. Respiratory and neuro-psychiatric symptom-load was significantly and negatively related to prescription of antidepressants and anticoagulants, respectively. Fatigue was negatively and positively related to RAAS-inhibitors and proton-pump-inhibitors, respectively. These significant relationships disappeared with p-value adjustment owed to multiple testing. The mean total psychiatric burden was not worsened across the study. Discussion None of the tested medications was significantly associated with the COVID-19-duration and -severity up to the end of post-diagnosing week 3. However, there were a few biologically plausible and promising relationships with antidepressants, anticoagulants, and RAAS-inhibitors before p-value adjustment. These should encourage larger and prospective studies to re-evaluate the influence of somatic and psychiatric routine medications on COVID-19-related health outcomes.

The interaction between cannabis use or addiction and SARS-COV-2 infection rates and COVID-19 outcomes is obscure. As of 08/01/2022 among 57 evaluated epidemiological/clinical studies found in Pubmed-database, most evidence for how cannabis use patterns were influenced by the pandemic was given by two systematic reviews and 17 prospective studies, mostly involving adolescents. In this age group, cannabis use patterns have not changed markedly. For adults, several cross-sectional studies reported mixed results with cannabis use having increased, decreased or remained unchanged. Two cross-sectional studies demonstrated that the severity of adults´ cannabis dependence was either increased as a consequence of increasing cannabis use during the pandemic or not changed. Regarding the effect of cannabis use on COVID-19 outcomes, we found only five retrospective/cross-sectional studies. Accordingly, (i) cannabis use did not impact mild COVID-19 symptoms; (ii) cannabis using individuals experienced more COVID-19-related hospitalizations; (iii) cannabis using veterans were associated with reduced SARS-COV-2 infection rates; (iv) frequent cannabis use was significantly associated with COVID-19 mortality, and (v) cannabis dependents were at higher risk of COVID-19 breakthrough after vaccination. It should be outlined that the validity of these retrospective/cross-sectional studies (all self-reports or register/e-health-records) is rather low. Future prospective studies on the effects of cannabis use on SARS-COV-2 infection rates and COVID-19 outcomes are clearly required for conclusive risk–benefit assessments of the role of cannabis on users’ health during the pandemic. Moreover, substance dependence (including cannabis) is associated with (often untreated) somatic comorbidity, which severity is a proven key risk factor for worse COVID-19 outcomes.

Background Internet-based self-help-programs like deprexis have been increasingly shown to reduce depressive symptoms if added to distinct, primarily outpatient-treatment-settings. There is limited information about the effectiveness of deprexis if started at routine psychiatric hospital inpatient treatment of moderate-to-severe major depressive disorder (MDD). Subjects and methods To examine, sixty-nine adult MDD-inpatients were randomly assigned to a 12-week-period of treatment-as-usual (TAU, N=33) or TAU plus guided deprexis (TAU-PLUS, N=36). The study was planned as a pragmatic approach considering psychiatric routine conditions, particularly, offering an instant and flexible discharge management when the patients felt stabilized enough for primary/secondary care. Therefore, there was no fixed time frame for the inpatient treatment duration. Post-discharge, patients were followed by structured telephone interviews up to study-endpoint, i. e., 12 weeks after deprexis-initiation. Primary (Beck-Depression-Inventory-II, BDI-II) and secondary outcome-measures (Hamilton-Depression-Scale, Clinical-Global-Impression-Severity, WHO-Well-Being-Index, Helping-Alliance-Questionnaire) were carried out at study entry and every 2 weeks. Furthermore, the working alliance with deprexis as well as the inpatient treatment duration, the daily activity and the utilization of post-hospital care after discharge were determined. Results At week 12, modified ITT-analyses showed significant between-group differences of BDI-II scores in favor of the TAU-PLUS-patients (p=.03) corresponding to a medium effect size (d=−.73, 95% CI −1.4 to .06). TAU-PLUS-patients showed greater daily activity (p=.04, d=.70, 95% CI −.03 to 1.38) and had been discharged significantly earlier from inpatient treatment (p=.003). Post-discharge, the TAU-PLUS-group reported a lower rate of post-hospital care (p=.01) and re-admissions (p=.04). Secondary outcome-measures including the alliance with the therapists were not significantly different between the groups at study-endpoint. The patients´ working-alliance with deprexis significantly predicted MDD-improvement and wellbeing. Both groups (TAU and TAU plus deprexis) were comparable with regard to the prescribed antidepressant medication. Unfortunately, detailed data on the amount and actual duration of the psychotherapeutic and special therapeutic individual and group settings of the TAU were not collected Conclusion TAU plus deprexis was superior to TAU in improving subjective depression-severity (BDI-II) and daily activity in patients having sought psychiatric inpatient MDD-treatment before. This beneficial effect appeared 12 weeks after inpatient deprexis-initiation, i. e. when the vast majority of patients were back in primary/secondary care. Adjunctive deprexis was associated with earlier discharges and a significant advantage for post-hospital stabilization. In this regard, it could be promising to include deprexis into inpatient treatment conditions, thereby also preparing its continuing outpatient use. We found no evidence that deprexis interfered negatively with the alliance between the patients and their therapists.

Over the past few years, there has been a growing concern about prescription opioid misuse and dependence in the elderly. Our study aimed to investigate the prevalence of previous and current prescription opioid dependence among elderly medical inpatients recruited from a large German hospital.This cross-sectional study analyzed a cohort of inpatients aged 65 years and older who were assessed with a structured clinical interview. Levels of past and current dependence on opioids benzodiazepines, hypnotics, and non-opioid analgesics were assessed.Of 2108 elderly inpatients admitted to the hospital during a 6-month period, 400 fulfilled the inclusion criteria and agreed to participate to the survey. Among these 400 subjects, 43 (10.8%) presented with a dependence on opioid analgesics, including 41 with current dependence and 22 (51.2%) with a de novo condition. Addiction severity was considered mild in 65.1% of cases and severe in 11.6% of cases. Tilidine and oxycodone were the most typically reported molecules.Further research is warranted, to better understand the possible risk factors of prescription drug misuse, abuse, and addiction in this vulnerable population. Clinicians should be updated and informed regarding both prescription medication misuse potential and safe prescribing practices in the elderly.

The treatment of patients diagnosed with a narcissistic personality disorder (NPS) is considered to be extra challenging. Well-controlled studies on the effectiveness of psychotherapy in NPS patients are not available; so many interventions are based on theoretical constructs. The clarification-oriented psychotherapy (COP) is a psychotherapeutic approach, which emerged from concepts of the cognitive behavioral therapy, client-centered psychotherapy and various process-oriented procedures. The present ambulatory therapy-evaluation of COP aimed to evaluate the effectiveness of a psychotherapeutic treatment for patients suffering from NPS. Retrospective cohort-study including 173 treatment-seeking NPS-patients. Via pre-post per-protocol-analysis, significant improvements mostly with medium effect sizes were found in all relevant parameters after completion of the COP (58.6±10.5 sessions). In particular, the ambitious/narcissistic personality style in the "Personality Style and Disorders Inventory (PSSI)" (primary outcome) was improved (medium effect size: d=-0.49 [-0.67; -0.31], As no intention-to-treat analysis has been carried out, the effect sizes of COP in the treatment of NPS might be overestimated. Nevertheless, our findings support the use of COP for the treatment of NPS. In light of evidence-based medicine, the present so far most comprehensive study on this topic warranted an increase of the evidence of COP in the treatment of NPS from level IV to level III. Patienten mit einer narzisstischen Persönlichkeitsstörung (NPS) gelten im Rahmen der therapeutischen Arbeit als besonders herausfordernd. Allerdings liegen gut kontrollierte Studien zur Effektivität von Psychotherapie bei NPS-Patienten bislang nicht vor, sodass viele Interventionsprozesse auf theoretischen Konstrukten basieren. Die Klärungsorientierte Psychotherapie (KOP) ist ein psychotherapeutisches Verfahren, welches sich aus Konzepten der Kognitiven Verhaltenstherapie, der Klientenzentrierten Psychotherapie und verschiedenen prozessorientierten Verfahren entwickelt hat. Die vorliegende Untersuchung versucht eine Quantifizierung der Effektivität einer psychotherapeutischen Behandlung der NPS per KOP. Retrospektive Kohorten-Studie. Die prä-post per-Protokoll-Analyse von 173 behandlungssuchenden NPS-Patienten1 zeigte nach Abschluss der Behandlung (58,6±10,5 Sitzungen) signifikante Verbesserungen von zentralen störungsrelevanten Parametern (mit größtenteils mittleren Effektstärken). Insbesondere das primäre Zielkriterium (d.h. der ehrgeizige/narzisstische Persönlichkeitsziel im „Persönlichkeits-Stil- und Störungs-Inventar“ (PSSI) zeigte eine positive Veränderung (mittlere Effektstärke: d=−0,49 [−0,67; −0,31], Da keine intention-to-treat-Analyse durchgeführt wurde, kann eine Überschätzung der Effektstärken der Behandlung nicht ausgeschlossen werden. Die Ergebnisse deuten an, dass der KOP eine bevorzugte Position bei der Behandlung der narzisstischen Persönlichkeitsstörung eingeräumt werden kann. Aus Sicht der evidenzbasierten Medizin unterstützen die Ergebnisse dieser bisher umfangreichsten Studie zur Psychotherapie der NPS eine Anhebung des Evidenzlevels der Wirksamkeit der KOP bei der Behandlung dieser Störung von Stufe IV auf Stufe III.

Background: Mammalian central neurons regulate their intracellular pH (pHi) strongly and even slight pHi-fluctuations can influence inter-/intracellular signaling, synaptic plasticity and excitability. Objective: For the first time, we investigated topiramate´s (TPM) influence on pHi- behavior of human central neurons representing a promising target for anticonvulsants and antimigraine drugs. Methods: In slice-preparations of tissue resected from the middle temporal gyrus of five adults with intractable temporal lobe epilepsy, BCECF-AM-loaded neocortical pyramidal-cells were investigated fluometrically. The pHi-regulation was estimated by using the recovery-slope from intracellular acidification after an ammonium-prepulse (APP). Results: Among 17 pyramidal neurons exposed to 50 µM TPM, seven (41.24%) responded with an altered resting-pHi (7.02±0.12), i.e. acidification of 0.01-0.03 pH- units. The more alkaline the neurons, the greater the TPM-related acidifications (r=0.7, p=0.001, n=17). The recovery from APP-acidification was significantly slowed under TPM (p Conclusion: TPM modulated the bicarbonate-driven pHi-regulation just as previously described in adult guinea-pig hippocampal neurons. We discussed the significance of the resulting subtle acidifications for beneficial antiepileptic, antimigraine and neuroprotective effects as well as for unwanted cognitive deficits. Study Limitations: Although these results are the only available pHi-measurements of human brain neurons to this issue, to the best of our knowledge, the study is limited by the small number of cells analyzed due to limited human material. Thus, the results presented here are preliminary data. Greater sample size is required to reach more reliable conclusions.”

Introduction Recent years have seen a dramatic escalation of off-label prescribing for gabapentin and pregabalin (gabapentinoids) owing in part to generic versions of each being released over the past two decades, but also in part as a response to increasing calls for multimodal and non-opioid pain management strategies. In this context, several recent articles have been published alleging widespread misuse, with speculations on the unappreciated addictive potential of the gabapentinoid class of drugs. Reports of a 1% population-level abuse prevalence stem from a single internet survey in the UK, and the vanishingly small adverse event outcomes data do not support such frequency. In this targeted narrative review, we aim to disabuse pain physicians and other clinicians, pharmacists, and policymakers of both the positive and negative myths concerning gabapentinoid medications. Results Gabapentinoids inhibit the joint action of voltage-gated calcium channel (VGCC) α2δ subunits in conjunction with the n-methyl-d-aspartate (NMDA) receptor, with subsequent downregulation of VGCC expression and excitatory neurotransmitter release, and possibly synaptogenesis as well, through actions on thrombospondins. These activities reduce the likelihood of central sensitization, which explains in part the efficacy of the gabapentinoids in the management of neuropathic pain. Gabapentinoids also facilitate slow-wave sleep, a relatively rare phenomenon among central nerve system-acting agents, which is also thought to explain some of the therapeutic benefit of the class in conditions such as fibromyalgia. The number needed to treat to see benefit overlaps that of the nonsteroidal anti-inflammatory drugs, but with a considerably improved safety profile. Along these lines, in the context of over 50 million prescriptions per year in the USA alone, the gabapentinoids display remarkably low risk, including risks of misuse, abuse, and dependence. Furthermore, the neurobiology of these agents does not lend plausibility to the allegations, as they have never been shown to elicit dopaminergic activity within the nucleus accumbens, and in addition likely confer a "negative-feedback loop" for habituation and dependence by serving as functional NMDA antagonists, possibly through their actions on thrombospondins. Clinical and epidemiological addictionology studies corroborate the lack of any significant addictive potential of the gabapentinoids, and these drugs are increasingly being used in the treatment of addiction to other substances, with excellent results and no evidence of cross-addiction. However, among individuals with other substance use disorders and, in particular opioid use disorder, there are consistent data showing misuse of gabapentinoids in up to 20% of this population. Although there are allegations of using gabapentinoids to amplify the hedonic effects of opioids, the vast majority of misuse events appear to occur in an attempt to ameliorate opioid withdrawal symptoms. Furthermore, rare but potentially serious respiratory depression may occur, again amplified in the context of opioid or other sedative use. Careful risk:benefit assessment and stratification are warranted when prescription of a gabapentinoid is under consideration, in particular among individuals using opioids. Conclusions Gabapentinoids remain a vital tool in the pain physician’s multimodal armamentarium, but these drugs may not be effective in every clinical situation. Individuals with central sensitization and pain associated with slow-wave sleep deficits and potentially persons with comorbid addictions may benefit the most. The gabapentinoids appear to possess no addictive potential on their own, based on laboratory and clinical data, but they may be abused by persons with opioid use disorders; consequently, cautious risk stratification must take place.

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.

Gabapentinoids (GPT) are reported to be increasingly misused by opioid- and polydrug-users, but the addictive potential of GPT outside of these populations remains understudied. Investigations comparing GPT abuse and dependence liability to that of other commonly prescribed Central Nervous System-acting medications are therefore warranted. We provide a comparison of GPT-abuse/dependence to that of other GABAmimetics within an elderly population.DSM-IV-TR-based data (previously prospectively collected by SKID-I-interview) from a random sample of elderly patients admitted to a metropolitan German general hospital were reviewed. The prevalence and severity of GPT, benzodiazepine (BDZ), and z-hypnotic drug (ZD)-abuse and -dependence were compared, stratified also by mono-substance (no concurrent current or previous substance use) and de novo-substance (first)-abuse and -dependence states.Among 400 patients (75 ± 6.4 years old; 63% females), neither current nor past abuse of BDZ, ZD or GPT, nor other illicit substances was observed. Dependence upon BDZ, ZD or GPT was observed among 55 (13.75%) individuals. The related lifetime/12-month prevalence-rates were: dependence condition (BDZ: 7%/2.45%; ZD: 4.25%/4.25%; GPT: 2.75/2.5%); mono-dependence condition (BDZ: 2.25%/0.75%; ZD: 1%/1%, GPT: 0%/0%); de novo-dependence condition (BDZ: 2.75%/1.75%; ZD: 1%/1%, GPT: 0.5%/0.5%). Opioid analgesic-dependence (N = 43/400) was significantly more frequently linked with BDZ than with GPT (p 0.01) [Correction added on 29 December 2021, after first online publication: In the sentence 'Opioid analgesic-dependence…', the term 'and ZD' has been deleted]. For all three GABAmimetic classes, most mono- and de novo-dependence states were mild-to-moderate and lasted 2-6 years (median).GABAmimetic-dependence was usually mixed with other substance-dependences. Every third to fourth instance of BDZ- or ZD-dependence was a mono-dependence condition, while a pure GPT-dependence was absent in this elderly (and illicit substance-naïve) population.

Background: Only a minority of subjects with substance use disorders (SUDs) are in addiction-specific treatment (treatment gap). Co-operation between an unemployment office and a psychiatric hospital was established for the assessment and counseling of long-term unemployed clients with SUD. We aim at validating whether such a treatment gap exists in that group, and whether clients from an unemployment office differed from a matched group of inpatient detoxification patients with regard to socio-economic characteristics, substance use and treatment history, and the prevalence of mental disorders Methods: Unemployment office clients (n = 166) with an SUD were assessed using a standardized sociodemographic and clinical interview. They were compared with 83 inpatients from a local detoxification ward, matched for age, sex, and primary addictive disorder (matching ratio 2:1). Results: Most (75.9%) subjects were males, with an average age of 36.7 years. The SUDs mostly related to alcohol (63.9%) and cannabis (27.7%). Although most unemployment office clients had a long SUD history, only half of them had ever been in addiction-specific treatment during their lifetime, and only one in four during the last year. There were no statistically significant differences between the groups regarding age at onset of problematic substance use, the proportion of migrants, and prevalence of comorbid mental disorders. The unemployment office sample showed lower levels of education (p < 0.001), job experience (p = 0.009), and current employment rates (p < 0.001). Conversely, inpatients showed lower rates of imprisonment (p < 0.001), more inpatient detoxification episodes (p < 0.03); and longer abstinence periods (p < 0.005). Conclusions: There was a lifetime and recent treatment gap in the group of long-term unemployed subjects with alcohol and cannabis dependence. The markedly lower educational attainment, chronic employment problems and higher degree of legal conflicts in the client group, as compared with patients in detoxification treatment, might require specific access and treatment options. The co-operation between the psychiatric unit and the unemployment office facilitated access to that group.

ZusammenfassungAnders als Spiritualität ist der Placebo-Effekt bestens operationalisiert. Vor diesem Hintergrund wird versucht, eine phänomenologische Verwandtschaft zwischen der therapeutischen Wirksamkeit von Spiritualität und Placebo zu finden. Ähnliche Kontexteinflüsse sowie die mögliche gemeinsame Nutzung einer phylogenetisch gut konservierten protektiven Route über das mesolimbisch dopaminerge Belohnungssystem werden herausgestellt. Die klinische Wirksamkeit beider Phänomene scheint ubiquitär zu sein, wobei die Effektivität des Placebo-Effektes wissenschaftlich viel valider abgesichert ist als dieses bezüglich eines „Spiritualität-Effektes“ aktuell methodologisch möglich wäre. Die Vorhersagbarkeit für beide Effekte ist unsicher und beide sind Janus-köpfig (z. B. Placebo vs. Nocebo-Effekt). Aktuell wird sowohl für Placebo als auch für spiritualitäts-orientierte Verfahren versucht, deren klinische Wirksamkeit durch Modulation der therapeutischen Rahmenbedingungen und Gesprächsinhalte zu maximieren. Die Diskussion endet mit der reflexiven Frage, ob der Placebo-Effekt im Wesentlichen Züge von „Spiritualität-light“ besitzen könnte.

In Europe, there have been several addiction-expert rankings of harms related to the use of psychotropic substances in the last 15 years. Among them, only one expert ranking took into account the potential benefits of these drugs. Non-Opioidergic Analgesics (NOAs), such as gabapentinoids and NSAIDs, which have been increasingly the subject of abuse / misuse reports, have not been considered in such expert rankings. Likewise, there is currently no multi-substance comparison as to whether the valuation rank of the harmfulness of an illegal drug may change along with an imagined change in legal status in Germany.Using a questionnaire, 101 experienced addiction physicians (first cohort) evaluated 33 psychoactive substances including analgesics with regard to their health and social harms as well as potential usefulness for the consumer and their environment / society ('others'). In addition, this cohort investigated whether the harmfulness assessment of an illegal substance changes if it would be legalized. In order to obtain the average overall harmfulness (overall risk) of a substance, the percentage contribution of each dimension to the overall harmfulness was determined in a second survey (second cohort, 36 experienced addiction medicine experts). Finally, the average benefit and overall risk ratings of each substance were related to each other.Prescription psychoactive substances such as analgesics, NOAs (including gabapentinoids) and opioidergic maintenance medications to treat opiate dependence were judged to have a favorable benefit-harm profile. Cannabis and ketamine were placed in the midfield of both, the harm and benefit rankings. Together with most illicit narcotic drugs, alcohol and nicotine, have been ranked among the most harmful and least useful substances, whereby alcohol was judged on average to be more harmful but also more useful than nicotine. In the event of potential legalization, the overall harm of the traditional illegal drugs methamphetamine, heroin, cocaine and cannabis was estimated to be reduced. This was mainly due to a more favorable valuation of the harm to others under these virtual conditions.Prescription substances including opioidergic and non-opioidergic analgesics as well as opioid maintenance therapy medications (methadone and buprenorphine) were assigned a favorable benefit-harm profile. Alcohol, nicotine and traditional illicit drugs (with the exception of cannabis and ketamine) were determined to have an unfavorable profile. The overall harm of traditional illicit drugs was assessed to decrease along with legalization, mainly by decreasing the harm to others in this virtual event.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.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.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.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.

CA extern

Background: Only a minority of subjects with substance use disorders (SUDs) are in addiction-specific treatment (treatment gap). Co-operation between an unemployment office and a psychiatric hospital was established for the assessment and counseling of long-term unemployed clients with SUD. We aim at validating whether such a treatment gap exists in that group, and whether clients from an unemployment office differed from a matched group of inpatient detoxification patients with regard to socio-economic characteristics, substance use and treatment history, and the prevalence of mental disorders Methods: Unemployment office clients (n = 166) with an SUD were assessed using a standardized sociodemographic and clinical interview. They were compared with 83 inpatients from a local detoxification ward, matched for age, sex, and primary addictive disorder (matching ratio 2:1). Results: Most (75.9%) subjects were males, with an average age of 36.7 years. The SUDs mostly related to alcohol (63.9%) and cannabis (27.7%). Although most unemployment office clients had a long SUD history, only half of them had ever been in addiction-specific treatment during their lifetime, and only one in four during the last year. There were no statistically significant differences between the groups regarding age at onset of problematic substance use, the proportion of migrants, and prevalence of comorbid mental disorders. The unemployment office sample showed lower levels of education (p < 0.001), job experience (p = 0.009), and current employment rates (p < 0.001). Conversely, inpatients showed lower rates of imprisonment (p < 0.001), more inpatient detoxification episodes (p < 0.03); and longer abstinence periods (p < 0.005). Conclusions: There was a lifetime and recent treatment gap in the group of long-term unemployed subjects with alcohol and cannabis dependence. The markedly lower educational attainment, chronic employment problems and higher degree of legal conflicts in the client group, as compared with patients in detoxification treatment, might require specific access and treatment options. The co-operation between the psychiatric unit and the unemployment office facilitated access to that group.

Background Over the last 15 years, a large number of new psychoactive substances (NPS) has been identified, with their use being associated with a range of acute medical and psychopathological complications. Conversely, NPS addictive liability levels have not been systematically assessed in clinical populations. Aims of the study Investigating the lifetime and current prevalence of NPS use in a sample of substance use disorder (SUD) patients admitted to an inpatient detoxification treatment centre. Methods Assessment of previous/current NPS intake carried out with the means of standardised questionnaire based on the European version of Addiction Severity Index. Results Some 206 patients (males 77.1%; average age: 30.7 years-old; most typical diagnosis: opioid/polydrug dependence) participated to the survey. Roughly half (e.g. 111/206; 53.9%) of them reported a lifetime use of NPS, most typically synthetic cannabinoids. Conversely, the current prevalence of NPS use was 2.9%; no NPS dependence condition was diagnosed. Among NPS users, 56.3% reported severe side-effects such as heavy anxiety or psychotic experience, and 64% reported an aversion of ever using the respective NPS again, whilst 84.3% of those reporting a single NPS intake reported an aversion. Discussion The sharp contrast between lifetime prevalence of NPS use and prevalence of current use might be explained by the high frequency of severe side effects reported by NPS users.

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/−12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders.

The intracellular pH (pHi) in the cytosol of mammalian central neurons is tightly regulated and small pHi-fluctuations are deemed to modulate inter-/intracellular signaling, excitability, and synaptic plasticity. The resting pHi of young rodent hippocampal pyramidal neurons is known to decrease alongside aging for about 0.1 pH-units. There is no information about the relationship between age and pHi of human central neurons. We addressed this knowledge gap using 26 neocortical slices from 12 patients (1-56-years-old) who had undergone epilepsy surgery. For fluorometric recordings, the slice-neurons were loaded with the pHi-sensitive dye BCECF-AM. We found that the pyramidal cells' resting pHi (n = 26) descended linearly alongside aging (r = - 0.71, p

Aims In cortical mammalian neurons, small fluctuations of intracellular pH (pHi) play a crucial role for inter- and intracellular signaling as well as for cellular and synaptic plasticity. Yet, there have been no respective data about humans. Thus, we investigated the interrelation of pHi and excitability of human cortical neurons. Materials and methods Intracellular electrophysiological and pH-recordings were made in neurons in slices taken from brain tissue resected from the middle temporal gyrus of two male children (26 months and 35 months old) who suffered from pharmacotherapy-resistant temporal lobe epilepsy. To excite the tissue (n = 13), we used the 0-Mg2+/high-K+-in vitro epilepsy model producing robust epileptiform discharges (ED). To evoke an intracellular acidification (n = 12), we used the well-established propionate-model and applied 10 mM propionate to the bath solutions. In addition, we recorded the effects of other strongly related short-chain monocarboxylates ( l -lactate (10 mM) and the ketone body DL-β-hydroxybutyrate (10 mM)) on ED and pHi. Key findings The ED-frequency was reversibly reduced by propionate (n = 5), l -lactate (n = 5), or DL-β-hydroxybutyrate (n = 3), while the durations of EDs and their after-depolarizations increased. In parallel experiments, all three short-chain monocarboxylates (each n = 4) lowered the pHi of the neurons (n = 12) by 0.05–0.07 pH units which was temporally related to the reported changes in bioelectric activity. Significance A mild drop of the intraneuronal pH was associated with the control of even over-excited human neocortical tissue. This is identical with prior observations in non-human mammalian cortical neurons. Possible implications for neuroplasticity and the treatment of neuropsychiatric disorders are discussed.