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Royal Society Open Science Mar 2017Emotional mimicry and empathy are mechanisms underlying social interaction. Benzodiazepines have been proposed to inhibit empathy and promote antisocial behaviour....
Emotional mimicry and empathy are mechanisms underlying social interaction. Benzodiazepines have been proposed to inhibit empathy and promote antisocial behaviour. First, we aimed to investigate the effects of oxazepam on emotional mimicry and empathy for pain, and second, we aimed to investigate the association of personality traits to emotional mimicry and empathy. Participants (=76) were randomized to 25 mg oxazepam or placebo. Emotional mimicry was examined using video clips with emotional expressions. Empathy was investigated by pain stimulating the participant and a confederate. We recorded self-rated experience, activity in major zygomatic and superciliary corrugator muscles, skin conductance, and heart rate. In the mimicry experiment, oxazepam inhibited corrugator activity. In the empathy experiment, oxazepam caused increased self-rated unpleasantness and skin conductance. However, oxazepam specifically inhibited neither emotional mimicry nor empathy for pain. Responses in both experiments were associated with self-rated empathic, psychopathic and alexithymic traits. The present results do not support a specific effect of 25 mg oxazepam on emotional mimicry or empathy.
PubMed: 28405353
DOI: 10.1098/rsos.160607 -
Chemosphere Jun 2017Pharmaceuticals as environmental contaminants have received a lot of interest over the past decade but, for several pharmaceuticals, relatively little is known about...
Pharmaceuticals as environmental contaminants have received a lot of interest over the past decade but, for several pharmaceuticals, relatively little is known about their occurrence in European surface waters. Benzodiazepines, a class of pharmaceuticals with anxiolytic properties, have received interest due to their behavioral modifying effect on exposed biota. In this study, our results show the presence of one or more benzodiazepine(s) in 86% of the analyzed surface water samples (n = 138) from 30 rivers, representing seven larger European catchments. Of the 13 benzodiazepines included in the study, we detected 9, which together showed median and mean concentrations (of the results above limit of quantification) of 5.4 and 9.6 ng L, respectively. Four benzodiazepines (oxazepam, temazepam, clobazam, and bromazepam) were the most commonly detected. In particular, oxazepam had the highest frequency of detection (85%) and a maximum concentration of 61 ng L. Temazepam and clobazam were found in 26% (maximum concentration of 39 ng L) and 14% (maximum concentration of 11 ng L) of the samples analyzed, respectively. Finally, bromazepam was found only in Germany and in 16 out of total 138 samples (12%), with a maximum concentration of 320 ng L. This study clearly shows that benzodiazepines are common micro-contaminants of the largest European river systems at ng L levels. Although these concentrations are more than a magnitude lower than those reported to have effective effects on exposed biota, environmental effects cannot be excluded considering the possibility of additive and sub-lethal effects.
Topics: Benzodiazepines; Clobazam; Environmental Monitoring; Europe; Oxazepam; Rivers; Temazepam; Water Pollutants, Chemical
PubMed: 28273540
DOI: 10.1016/j.chemosphere.2017.02.126 -
Journal of Forensic Sciences Nov 2017Sampling site, technique, and time influence postmortem drug concentrations. In 57 cases, we studied drug concentration differences as follows: subclavian...
Site-, Technique-, and Time-Related Aspects of the Postmortem Redistribution of Diazepam, Methadone, Morphine, and their Metabolites: Interest of Popliteal Vein Blood Sampling.
Sampling site, technique, and time influence postmortem drug concentrations. In 57 cases, we studied drug concentration differences as follows: subclavian vein-dissection/clamping versus blind stick, femoral vein-dissection/clamping versus blind stick, right cardiac chamber, and popliteal vein-dissection and clamping only. Cases were distributed in group #1 (all cases with both techniques), group #2 (dissection/clamping), and group #3 (blind stick). Sampled drugs were diazepam, methadone, morphine, and their metabolites. To assess PMR, mean concentrations and ratios were calculated for each group. Time-dependent variations of blood concentrations and ratios were also assessed. Results indicate that site, method, and time may influence postmortem distribution interpretation in different ways. Popliteal blood seems less subject to PMR. In conclusion, our study is the first to evaluate concurrently three main aspects of PMR and confirms that the popliteal vein may represent a site that is more resistant to the changes seen as a result of PMR.
Topics: Adult; Blood Specimen Collection; Chromatography, Liquid; Diazepam; Female; Femoral Vein; Forensic Toxicology; Humans; Male; Methadone; Middle Aged; Morphine; Morphine Derivatives; Nordazepam; Oxazepam; Popliteal Vein; Postmortem Changes; Subclavian Vein; Young Adult
PubMed: 28105644
DOI: 10.1111/1556-4029.13404 -
Nature Communications Dec 2016Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are...
Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABA receptor function.
Topics: Animal Migration; Animals; Anti-Anxiety Agents; Circadian Rhythm; Muscles; Oxazepam; Salmo salar; Time Factors; Water; gamma-Aminobutyric Acid
PubMed: 27922016
DOI: 10.1038/ncomms13460 -
Archives of Environmental Contamination... Oct 2016This study is the first to investigate the pharmaceutical burden from point sources affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike, Sweden. The...
This study is the first to investigate the pharmaceutical burden from point sources affecting the UNESCO Biosphere Reserve Kristianstads Vattenrike, Sweden. The investigated Biosphere Reserve is a >1000 km(2) wetland system with inflows from lakes, rivers, leachate from landfill, and wastewater-treatment plants (WWTPs). We analysed influent and treated wastewater, leachate water, lake, river, and wetland water alongside sediment for six model pharmaceuticals. The two WWTPs investigated released pharmaceutical residues at levels close to those previously observed in Swedish monitoring exercises. Compound-dependent WWTP removal efficiencies ranging from 12 to 100 % for bendroflumethiazide, oxazepam, atenolol, carbamazepine, and diclofenac were observed. Surface-water concentrations in the most affected lake were ≥100 ng/L for the various pharmaceuticals with atenolol showing the highest levels (>300 ng/L). A small risk assessment showed that adverse single-substance toxicity on aquatic organisms within the UNESCO Biosphere Reserve is unlikely. However, the effects of combinations of a large number of known and unknown pharmaceuticals, metals, and nutrients are still unknown.
Topics: Conservation of Natural Resources; Environmental Monitoring; Pharmaceutical Preparations; Water Pollutants, Chemical; Wetlands
PubMed: 27480162
DOI: 10.1007/s00244-016-0303-7 -
Forensic Science International Sep 2016Powdered roots of iboga (Tabernanthe iboga) contain ibogaine, an alkaloid that has been used to treat addictions. We report the case of a 30-year-old woman who died...
Powdered roots of iboga (Tabernanthe iboga) contain ibogaine, an alkaloid that has been used to treat addictions. We report the case of a 30-year-old woman who died after ingesting a powder labeled as Tabernanthe iboga she had bought online. Analysis of the powder revealed the absence of ibogaine but the presence of toxic alkaloids (ajmaline, yohimbine and reserpine) found in Rauvolfia sp. plant species. An original and specific LC-MS/MS method developed to quantify ajmaline, yohimbine and reserpine showed respective concentrations of 109.1ng/mL, 98.2ng/mL and 30.8ng/mL in blood, and 1528.2ng/mL, 914.2ng/mL and 561.2ng/mL in bile. Moreover, systematic toxicological analyses of biological samples showed the presence of oxazepam at therapeutic concentration and cannabinoids. Death could be attributed to ingestion of a substantial quantity of crushed roots of Rauvolfia in association with concomitant drug withdrawal.
Topics: Adult; Chromatography, Liquid; Female; Forensic Toxicology; Humans; Powders; Product Labeling; Rauwolfia; Secologanin Tryptamine Alkaloids; Tandem Mass Spectrometry
PubMed: 27342343
DOI: 10.1016/j.forsciint.2016.06.014 -
BMC Psychiatry Mar 2016Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as...
BACKGROUND
Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical similarity between olanzapine and clozapine, we hypothesized the existence of such an association. We searched the spontaneous adverse drug reports database of the Danish Health and Medicines Authority for olanzapine and myocarditis in the period from October 21, 1996 to - June 03, 2015. We identified two fatal cases of eosinophilic myocarditis associated with the use of olanzapine.
CASE PRESENTATION
Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current treatment was olanzapine 20 mg/day +5 mg as PRN (prescribed for almost 4 years), aripiprazole 30 mg/day (prescribed for 6 months) and mirtazapine 30 mg/day (prescribed for 6 months). Both cases of eosinophilic myocarditis were confirmed by autopsy findings and both patients received olanzapine in doses exceeding the recommendations.
CONCLUSION
Olanzapine may have contributed to and/or worsened the two reported fatal cases of myocarditis. Additional studies are required to establish a causal link between olanzapine and eosinophilic myocarditis.
Topics: Adult; Antipsychotic Agents; Benzodiazepines; Eosinophilia; Fatal Outcome; Humans; Male; Myocarditis; Olanzapine; Schizophrenia
PubMed: 26988850
DOI: 10.1186/s12888-016-0776-y -
The British Journal of General Practice... Apr 2016Drug dependency may develop during long-term benzodiazepine use, indicated, for example, by dose escalation. The first benzodiazepine chosen may affect the risk of dose... (Observational Study)
Observational Study
BACKGROUND
Drug dependency may develop during long-term benzodiazepine use, indicated, for example, by dose escalation. The first benzodiazepine chosen may affect the risk of dose escalation.
AIM
To detect possible differences in benzodiazepine use between new users of diazepam and oxazepam over time.
DESIGN AND SETTING
This 5-year prescription database study included 19 747 new benzodiazepine users, inhabitants of Norway, aged 30-60 years, with first redemption for diazepam or oxazepam.
METHOD
Individuals starting on diazepam versus oxazepam were analysed by logistic regression with sex, age, other drug redemptions, prescriber's specialty, household income, education level, type of work, and vocational rehabilitation support as background variables. Time to reach a daily average intake of ≥1 defined daily doses (DDD) over a 3-month period was analysed using a Cox proportional hazard regression model.
RESULTS
New users of oxazepam had a higher risk for dose escalation compared with new users of diazepam. This was true even when accounting for differences in sociodemographic status and previous drug use (hazard ratio [HR] 1.33, 95% confidence interval = 1.17 to 1.51).
CONCLUSION
Most doctors prescribed, according to recommendations, oxazepam to individuals they may have regarded as prone to and at risk of dependency. However, these individuals were at higher risk for dose escalation even when accounting for differences in sociodemographic status and previous drug use. Differences between the two user groups could be explained by different preferences for starting drug, DDD for oxazepam being possibly too low, and some unaccounted differences in illness.
Topics: Adult; Anti-Anxiety Agents; Anxiety; Depression; Diazepam; Dose-Response Relationship, Drug; Drug Prescriptions; Female; Follow-Up Studies; Humans; Male; Middle Aged; Norway; Oxazepam; Prescription Drug Misuse; Prevalence; Proportional Hazards Models; Risk Factors; Substance-Related Disorders
PubMed: 26965028
DOI: 10.3399/bjgp16X684385 -
Journal of Analytical Toxicology Apr 2016Liquid chromatography-tandem mass spectrometry (LC-MS-MS) offers specific advantages over gas chromatography-mass spectrometry (GC-MS) such as the ability to identify... (Comparative Study)
Comparative Study
Liquid chromatography-tandem mass spectrometry (LC-MS-MS) offers specific advantages over gas chromatography-mass spectrometry (GC-MS) such as the ability to identify and measure a broader range of compounds with minimal sample preparation. Comparative analysis of LC-MS-MS versus GC-MS was performed for urinalysis detection of five benzodiazepine compounds currently part of the Department of Defense (DoD) Drug Demand Reduction Program (DDRP) testing panel; alpha-hydroxyalprazolam, oxazepam, lorazepam, nordiazepam and temazepam. In the analyses of internally prepared control urine samples at concentrations around the DDRP administrative decision point for benzodiazepines (100 ng/mL), both technologies produced comparable results with average accuracies between 99.7 and 107.3% and average coefficients of variation (%CV) <9%. Analysis of service member specimens that screened positive for benzodiazepines using both technologies produced comparable results for all analytes. Different degrees of matrix effect were observed for all analytes in the LC-MS-MS analysis. However, the effects were controlled by using deuterated internal standards (ISTDs). Additionally, there was a 39% increase in nordiazepam mean concentration analyzed by LC-MS-MS due to suppression of the ISTD ion by the flurazepam metabolite 2-hydroxyethylflurazepam. The ease and speed of sample extraction, the broader range of compounds that can be analyzed and shorter run time make the LC-MS-MS technology a suitable and expedient alternative confirmation technology for benzodiazepine testing.
Topics: Benzodiazepines; Chromatography, Liquid; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Tandem Mass Spectrometry
PubMed: 26755538
DOI: 10.1093/jat/bkv140