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Forensic Chemistry (Amsterdam,... Sep 2023An LC-MS/MS method for the analysis of 53 benzodiazepines, including various designer benzodiazepines, was developed. The developed method was applied to a total of 79...
An LC-MS/MS method for the analysis of 53 benzodiazepines, including various designer benzodiazepines, was developed. The developed method was applied to a total of 79 illicit street drug samples collected in Chicago, IL. Of these samples, 68 (84%) had detectable amounts of at least one benzodiazepine. Further, of the 53 benzodiazepines included in the developed method just 14 were measured in samples. Clonazolam, a potent designer benzodiazepine and derivative of clonazepam, was the most frequently measured benzodiazepine in 63% of samples and was measured in the highest concentrations. Other benzodiazepines measured in more than 10% of samples included clonazepam, alprazolam, flualprazolam, and oxazepam. Mixtures of benzodiazepines were frequently measured in samples, with just 24% of samples containing just one benzodiazepine. To determine the response of benzodiazepines on a rapid, point-of-use drug checking tool, all 53 benzodiazepine standards were screened on a lateral flow immunoassay benzodiazepine test strip. Sixty eight percent of standards gave a positive BTS response at a concentration of 20 μg/mL, demonstrating BTS have response to a wide variety of benzodiazepines, including many designer benzodiazepines. A comparison of this data to previous data reported for the same samples demonstrated all samples containing a benzodiazepine also had an opioid present, with fentanyl being present in 94% of benzodiazepine samples. These results highlight high rates of polysubstance drug presence in Chicago, IL illicit drug samples, posing an increased risk of drug overdoses in people who use drugs.
PubMed: 37483533
DOI: 10.1016/j.forc.2023.100512 -
Evidence-based Complementary and... 2023[This retracts the article DOI: 10.1155/2022/2344946.].
[This retracts the article DOI: 10.1155/2022/2344946.].
PubMed: 37387975
DOI: 10.1155/2023/9821717 -
European Journal of Clinical... Sep 2023To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To compare the efficacy and safety of non-benzodiazepines (non-BZDs) to benzodiazepines (BZDs) in the treatment of alcohol withdrawal syndrome (AWS).
METHODS
For relevant literature, Google Scholar, PubMed, Embase, OVID MEDLINE, EBSCO, Cochrane Central Registry of Controlled Trials, Web of Science, and Scopus were searched. Randomized control trials (RCTs) were included, omitted were nonblinded trials, blinded trials that were not randomized, and open-label studies. The Effective Public Health Practice Project Quality Assessment was used to assess the trial's quality. A meta-analysis and a narrative synthesis were carried out.
RESULTS
Twenty non-BZDs and five BZDs were investigated in thirty RCTs. Meta-analysis favored gabapentin over chlordiazepoxide and lorazepam (d = 0.563, p < 0.001) and carbamazepine over oxazepam and lorazepam (d = 0.376, p = 0.029), for reducing Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scale scores. Eleven non-BZDs fared better than BZDs for reducing CIWA-Ar, Total Severity Assessment, Selective Severity Assessment, Borg and Weinholdt, and Gross Rating Scale for Alcohol Withdrawal scores. Eight non-BZDs outmatched BZDs regarding autonomic, motor, awareness, and psychiatric symptoms. Sedation and fatigue were prevalent in BZDs, while seizures were prevalent in non-BZDs.
CONCLUSION
For AWS treatments, non-BZDs are superior to or equally effective as BZDs. Non-BZD adverse events warrant further investigation. Agents that inhibit gated ion channels are promising candidates.
PROTOCOL REGISTRATION
PROSPERO CRD42022384875.
Topics: Humans; Alcoholism; Benzodiazepines; Ethanol; Lorazepam; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 37380897
DOI: 10.1007/s00228-023-03523-2 -
Ecotoxicology and Environmental Safety Jul 2023Pharmaceutically active compounds are common and increasing in the aquatic environment. Evidence suggests they have adverse effects on non-target organisms, and they are...
Pharmaceutically active compounds are common and increasing in the aquatic environment. Evidence suggests they have adverse effects on non-target organisms, and they are classified as emerging pollutants for a variety of aquatic organisms. To determine the effects of environmentally relevant levels of psychoactive compounds on non-target organisms, we analyzed cardiac and locomotory activity in early developmental stages of marbled crayfish Procambarus virginalis. Responses to sertraline, methamphetamine, and a mixture of citalopram, oxazepam, sertraline, tramadol, venlafaxine, and methamphetamine at a concentration of 1 µg L of each compound were assessed. On day four of exposure, cardiac activity was recorded for 5 min, and on day eight, locomotory activity was recorded for 15 min. There was a significant increase (p < 0.01) in heart rate in methamphetamine-exposed and Mix-exposed juveniles compared to the unexposed control and there was significant difference (p < 0.01) in proportion of time (activity %) was observed with sertraline-exposed, whereas velocity, and distance moved did not significantly differ (p > 0.05) in exposed and control animals. These findings revealed that low concentrations of chemicals and their mixtures can modify the physiological state of aquatic animals without outward manifestations (activity, distance moved, and velocity). Aquatic animals can be impacted earlier than is visible, but effects can potentially lead to substantial changes in populations and in ecosystem processes. Additional research to investigate chemical combinations, exposure systems, and organism physiological and molecular responses may provide evidence of broad impact of environmental pharmaceuticals.
Topics: Animals; Astacoidea; Ecosystem; Sertraline; Methamphetamine; Locomotion; Water Pollutants, Chemical
PubMed: 37267780
DOI: 10.1016/j.ecoenv.2023.115084 -
The Science of the Total Environment Sep 2023The presence of pharmaceuticals (PHA) and narcotics (NAR) in wastewater (WW) has attracting growing interest due to concern for aquatic environment and the possibility...
Pharmaceutical and narcotics monitoring in Brno wastewater system and estimation of seasonal effect on the abuse of illicit drugs by a wastewater-based epidemiology approach.
The presence of pharmaceuticals (PHA) and narcotics (NAR) in wastewater (WW) has attracting growing interest due to concern for aquatic environment and the possibility to exploit their presence to estimate drug consumption by population. This work aims to (i) quantify PHA and NAR in the WW of the Brno metropolitan area, (ii) determine the effectiveness of the current conventional wastewater treatment plant (WWTP), and (iii) estimate the illicit drug (ID) consumption. 23 PHA and 9 NAR were frequently detected in the untreated WW and studied for their removal. One year monitoring was carried out to highlight a possible seasonal pattern with PHA and NAR load in WW, WWTP effectiveness, and illicit consumption. Results highlighted that the most abundant PHA and NAR were caffeine (73.9 ± 6.9 μg L) and methamphetamine (2.3 ± 0.1 μg L) while oxazepam (0.13 ± 0.05 μg L) and EDDP (0.02 ± 0.01 μg L) were the lowest ones, respectively. Only paracetamol, caffeine, atenolol, ciprofloxacin, amphetamine, cocaine, morphine, and benzoylecgonine exhibited a high biodegradability being removed almost completely (> 90 %). A predominant illicit use of methamphetamine was estimated (17 ± 0.6 doses 1000.inh d) that might suggest a higher number of consumers than previous official estimation. A lower abuse of cocaine (2.7 ± 0.5 doses 1000.inh d), amphetamine (2.2 ± 0.3 doses 1000.inh d), methadone (1.1 ± 0.2 doses 1000.inh d), heroin (0.9 ± 0.2 doses 1000.inh d), and MDMA (0.7 ± 0.1 doses 1000.inh d) was found. A seasonality pattern was highlighted for some PHA and NAR influent load and removal, and, about ID consumption, only for heroin and methadone. These results will be useful for water utilities, to enhance the knowledge about the presence and removal of PHA and NAR, and local and national authorities to evaluate and counteract the problem of ID abuse.
Topics: Humans; Wastewater; Illicit Drugs; Narcotics; Wastewater-Based Epidemiological Monitoring; Heroin; Seasons; Caffeine; Water Pollutants, Chemical; Environmental Monitoring; Amphetamine; Methamphetamine; Cocaine; Methadone; Substance Abuse Detection; Substance-Related Disorders
PubMed: 37263433
DOI: 10.1016/j.scitotenv.2023.164386 -
Addiction (Abingdon, England) Oct 2023The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the...
AIMS
The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10 years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France.
DESIGN
This was a nation-wide, repeated cross-sectional study.
SETTING AND PARTICIPANTS
Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use).
MEASUREMENTS
The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug.
FINDINGS
The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6 DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1 DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/.
CONCLUSIONS
In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.
Topics: Prescription Drug Misuse; Prescription Drugs; Cross-Sectional Studies; Psychotropic Drugs; France; Humans; Office Visits
PubMed: 37203878
DOI: 10.1111/add.16261 -
Bioaccumulation as a method of removing psychoactive compounds from wastewater using aquatic plants.Journal of Chromatography. B,... May 2023Since WWTPs are not able to eliminate all psychoactive pharmaceuticals, these compounds become a part of the aquatic ecosystem. Our results indicate that compounds such...
Since WWTPs are not able to eliminate all psychoactive pharmaceuticals, these compounds become a part of the aquatic ecosystem. Our results indicate that compounds such as codeine or citalopram are eliminated with low efficiency (<38%), and compounds such as venlafaxine, oxazepam, or tramadol even with almost no efficiency. Lower elimination efficiency may be caused by the accumulation of these compounds in the wastewater treatment process. This study is focused on the possibility to remove problematic psychoactive compounds using aquatic plants. HPLC-MS analysis of the leaf extract obtained from studied plants showed that the amount of accumulated methamphetamine was highest in Pistia stratiotes and lower in the leaves of Limnophila sessiliflora and Cabomba caroliniana. However, tramadol and venlafaxine were accumulated considerably only in Cabomba caroliniana. Our study demonstrates that especially these three compounds - tramadol, venlafaxine, and methamphetamine, are accumulated in aquatic plants and can be removed from the aquatic environment. In our study was also observed that helophytic aquatic plants show a higher ability to remove psychoactive compounds from wastewater. Iris pseudacorus showed the best results in selected pharmaceuticals removal with no bioaccumulation effect in leaves or roots.
Topics: Wastewater; Tramadol; Venlafaxine Hydrochloride; Ecosystem; Water Pollutants, Chemical; Plants; Methamphetamine; Pharmaceutical Preparations; Environmental Monitoring
PubMed: 37148853
DOI: 10.1016/j.jchromb.2023.123717 -
Journal of Analytical Toxicology Jul 2023Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of...
Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of this study was to investigate the influence of lipemia on postmortem analysis as well as demonstrate the usage of Intralipid in comparison to pooled postmortem lipids as matrix additives for meaningful evaluation and validation of hyperlipidemic postmortem samples. Hyperlipidemic blood samples were simulated by adding different concentrations of Intralipid or pooled authentic postmortem lipids to bovine whole blood. The hyperlipidemic blood samples were spiked with 14 benzodiazepines and five sedative and antianxiety drugs (alprazolam, clonazepam, 7-aminoclonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, hydroxyzine, lorazepam, midazolam, nitrazepam, 7-aminonitrazepam, nordazepam, oxazepam, propiomazine, dihydropropiomazine, temazepam, triazolam, zolpidem and zopiclone). Samples were prepared with liquid-liquid extraction followed by ultra-high performance liquid chromatography-mass spectrometry. The effects of lipemia on the recovery of analytes and internal standards (ISs) were evaluated to determine the effect of, and any differences between, the two additives. Lipemia was found to cause major interference when quantifying the analytes. For most analytes, the ISs could compensate for analyte losses. However, the most hydrophilic analytes (7-amino metabolites), together with the most lipophilic analytes (propiomazine and dihydropropiomazine), were greatly affected by lipemia (<50% recovery), and the IS could not compensate for analyte losses. In general, lower analyte recoveries were observed for samples with Intralipid as a lipemic additive in comparison to those containing pooled postmortem lipids. Both Intralipid and pooled postmortem lipids showed marked effects on the analytical results. Intralipid gave a good indication of the effects of lipemia and could be a useful tool for making a meaningful evaluation of hyperlipidemic postmortem samples during the method development and validation.
Topics: Animals; Cattle; Tandem Mass Spectrometry; Benzodiazepines; Phospholipids; Hyperlipidemias
PubMed: 37130054
DOI: 10.1093/jat/bkad025