[Weighing the benefits and harms of psychotropic and analgesic substances - A perspective of German addiction medicine experts]. / Abwägung von Nutzen und Schädlichkeit von berauschenden und schmerzlindernden Substanzen aus der Perspektive von deutschen Suchtmedizinern.

BACKGROUND: 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. OBJECTIVES AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Novel Synthetic Opioids (NSO) Use in Opioid Dependents Entering Detoxification Treatment.

Introduction: Over 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. Method: A 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. Results: Sample 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. Discussion: NSO 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.

Prediction of the outcome of inpatient opiate detoxification treatment: results from a multicenter study.

BACKGROUND: Monocentric studies of inpatient opiate detoxification treatment show considerable variability regarding treatment success rates. This multicentric study investigates whether patient characteristics explain the different rates of regular discharge between treatment units. METHODS: 1,017 opiate-dependent patients from 12 detoxification units with similar treatment programs, funding, staffing and equipment were analyzed. Patient data and outcomes were documented by treatment staff using a standard form. RESULTS: Controlling for center, regular discharge (range: 14-49% between centers) was significantly associated with pre-existing plans for follow-up treatment, previous completed long-term residential and detoxification treatments, fewer unsuccessful detoxification treatments, higher age, later onset of opiate use, and longer duration of use. Controlling for patient characteristics, the center variable was significantly associated with outcome in a multiple logistic regression analysis. CONCLUSIONS: Regular discharge could best be predicted by patients' plans for follow-up treatment and previous treatment outcomes. Although treatment units had equivalent resources and regulations, and although patient effects were statistically controlled for, there were still considerable center effects. Setting factors as well as actual drop-out processes should be investigated more closely in the future.

Corrigendum: Prevalence of Novel Psychoactive Substance (NPS) Use in Patients Admitted to Drug Detoxification Treatment.

[This corrects the article DOI: 10.3389/fpsyt.2020.00569.].

Prevalence of Novel Psychoactive Substance (NPS) Use in Patients Admitted to Drug Detoxification Treatment.

BACKGROUND: About 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. OBJECTIVE: We investigated lifetime and recent use of NPS and other drugs in patients who underwent in-patient detoxification treatment from illicit drugs in Germany. METHODS: In 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. RESULTS: Interviews 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. CONCLUSION: Patients 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.

Ranking the Harm of Psychoactive Drugs Including Prescription Analgesics to Users and Others-A Perspective of German Addiction Medicine Experts.

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.

[Opioid Maintenance for Patients in Inpatient Long-Term Rehabilitation Treatment - which Patients Benefit?] / Substitution Opiatabhängiger im Rahmen der stationären Rehabilitationsbehandlung ­ welche Patienten profitieren?

OBJECTIVE: Patients from opioid maintenance treatment (OMT) may taper off from opioids during rehab treatment. It is investigated whether this option improves treatment outcomes in particular for those patients who are affected by psychiatric or somatic comorbidity, or by social problems. METHODS: Multicenter study with 4 rehab units. Patient characteristics and treatment outcomes were collected retrospectively. There were n = 227 patients who were admitted to treatment while still receiving OMT, and n = 156 who were opioid free. RESULTS: With regard to regular completion of rehab treatment, an interaction was observed between status at admission and diagnosis of affective, neurotic and anxiety disorders, and between status and previous rehab treatment experience. If admitted in an abstinent status, patients who had never entered rehab, and patients with affective or anxiety disorders showed decreased regular completion rates, while they showed increased completion rates if tapered off during treatment. There was no interaction between initial status and acute life crisis (release from prison, homelessness), somatic diagnoses, or number of stabilizing social factors. CONCLUSION: Admission while still receiving opiate maintenance could be helpful for patients with psychiatric comorbidity and for patients who had previously been reluctant to enter rehab treatment.

Prevalence and risk factors of syphilis infection among drug addicts.

BACKGROUND: Recent epidemiological data show an increased trend of official estimates for syphilis infection in the general population. Many of the infected cases remain undetected leaving an underestimation of the true prevalence of syphilis in the general population, but also among subpopulations such as illicit drug users. There is limited epidemiological data published on the proportion and risk factors of syphilis infections associated with illicit drug abuse. METHODS: Illicit drug addicts (n = 1223) in inpatients units in Germany were screened (2000-01) for syphilis and interviewed regarding patterns of drug use and sexual behaviour. TPHA-test for initial screening and FTA-ABS-IgM test in TPHA-positive patients were used. RESULTS: In total, TPHA-tests were positive in 39 (3.3%) and 7 patients (0.6%) were IgM positive. The prevalence rate for syphilis in males was 1.9% and for women it was 8.5%. Female patients were 4.56 (CI 95% 2.37-8.78) times more likely to have a positive TPHA test than males. Sexual behaviours such as high number of sexual partners, sex for drugs/money, sex on the first day were associated with syphilis infection only in women. Females with frequent sex for drugs or money had 4.31 (CI 95% 2.32-8.52) times more likely a reactive TPHA test than remaining patients. Neither the sociodemographic factors nor sexual behaviour were statistically significant associated with syphilis infection among men at all. CONCLUSION: Our data suggest the need for screening for syphilis among these illicit drug users in inpatient settings, in particular among sexual active women. This conclusion is corroborated by the finding of increasing numbers of syphilis infections in the general population. The identification of syphilis cases among drug addicts would give treatment options to these individuals and would help to reduce the spread of infection in this population, but also a spread into heterosexual populations related to prostitution.

Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR): tools to predict in vivo bioavailability from orally applied drug suspensions.

Low solubility of drug candidates generated in research contributes to their elimination during subsequent development due to insufficient oral bioavailability (BA) of crystalline compound. Therefore, the purpose of the study was to identify critical in vitro solubility and dissolution parameter that would predict critical in vivo dissolution by means of in vitro-in vivo correlation. Thermodynamic solubility and apparent dissolution rate (ADR) were determined using the shake-flask method and mini-flow-through-cell, respectively. Oral BA studies in rats and humans were conducted from drug solution and suspension/tablets. Relative BA was calculated using F(rel) [%]=AUC(suspension)/AUC(solution)*100, representing a measure of in vivo dissolution. Roughly, F(rel) rat >50% translates into F(rel) human of >90%. Both, ADR and log volume to dissolve applied dose (VDAD), when plotted against F(rel) rat, revealed certain threshold levels, (ADR, ∼150-200 µg of compound dissolved under respective assay conditions; VDAD, ∼100-500 ml/kg) which translate into F(rel) in rats of >50%. Thus, assuming that F(rel)>50% in rats is indicative of sufficient in vivo dissolution in humans after oral application, drugs should exhibit a VDAD of ∼100-500 ml/kg or less in aqueous media to avoid insufficient or varying drug absorption.

The effects of combined acamprosate and integrative behaviour therapy in the outpatient treatment of alcohol dependence: a randomized controlled trial.

AIMS: The aim of this randomized, controlled, multisite trial was to evaluate the efficacy of combined treatment with integrative behaviour therapy (IBT) and acamprosate on drinking behaviour in detoxified alcohol-dependent patients. METHODS: A total of 371 patients were randomized to one of the three treatment conditions: IBT plus acamprosate, IBT plus placebo, or supportive counselling ('treatment as usual', TAU) plus acamprosate. The main outcome was success rate, i.e., rate of abstinence plus improvement according to the criteria of Feuerlein and Küfner (1989), at the end of the six-month treatment phase and at the subsequent six-month follow-up. Drinking status was validated by blood parameters (CDT, GGT, and MCV). Data were analyzed by an intent-to-treat model and missing data were classified as relapse. RESULTS: The success rates at the end of treatment under both TAU plus acamprosate (37.7%) and IBT plus placebo (48%) almost reached the levels derived from the literature. However, adding acamprosate to IBT did not result in the expected increase in success rate (IBT plus acamprosate: 47.6%), and success rates did not differ significantly between groups. Similarly, there was no significant difference between treatment success rates at follow-up. CONCLUSION: The results suggest that the combination of acamprosate and IBT is not more effective than treatment with either IBT or acamprosate alone. However, the two acamprosate conditions differed in success rate by about 10%, which might constitute a clinically relevant though statistically non-significant effect.

Chromium-scandium multilayer mirrors for the nitrogen K(alpha) line in the water window region.

Chromium-scandium (Cr-Sc) is a promising material combination for multilayer mirrors in the water window region. A possible x-ray source for laboratory use in this wavelength range is the nitrogen K(alpha) line at 3.16 nm. High reflectivities at this wavelength can be achieved with Cr-Sc multilayer mirrors if the interfaces between adjacent layers are smooth. The growth parameters of the magnetron sputtering process for these materials have been optimized. It is shown that the reflectivity of such mirrors can be considerably improved by the application of a proper bias voltage during film growth. The high quality of the multilayer films is demonstrated with copper K(alpha) x-ray reflection and transmission electron microscopy. The reflective properties of the multilayers close to the nitrogen K(alpha) line were measured with synchrotron radiation for different angles of incidence. Reflectivities between R = 5.9% for near-normal incidence (theta = 1.5 degrees) and R = 29.6% for theta = 59.9 degrees were measured.