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Purpose: Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography–tandem mass spectrometry (LC–MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ9-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline). Methods: The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC–MS/MS was applied to forensic autopsy samples after thorough validation. Results: We found that the recombinant β-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC–MS/MS-based calibration curves processed with this method showed good linearity, with r2 values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0–109.7% and 0.8–8.8%, respectively. The recovery efficiencies were in the range of 56.1–104.5%. Matrix effects were between 78.9 and 126.9%. Conclusions: We have established an LC–MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations. [ABSTRACT FROM AUTHOR]

Objective: Alternatives to conventional acute hospitalizations have been particularly useful during the COVID-19 pandemic. However, little is known on the management and outcomes of COVID-19 in older patient admitted to non-acute settings. The main aim of this study was to determine the effect of geriatrics syndromes on functional outcomes in older COVID-19 patients cared in sub-acute units. Methods: Prospective multicenter observational cohort study of patients aged 65 years and older with COVID-19, admitted to sub-acute units in Italy and Spain. Multivariable logistic regression models were used to test the association between geriatric syndromes and other clinical variables, and the functional status at discharge, defined by a Barthel Index > = 80. Results: A total of 158 patients were included in the study with a median age of 82 [Interquartile Range 81, 83]; of these 102 (65%) patients had a Barthel Index ≥ 80 at discharge. In the main multivariable logistic regression model a higher severity of frailty-measured with the Clinical Frailty Scale—(OR 0.30; CI 0.18–0.47), and the presence of delirium (OR 0.04; CI 0.00–0.35) at admission were associated with lower odds of a higher functional status at discharge. Other variables associated with lower functional status were female gender (OR 0.36; CI 0.13–0.96), and a higher number of comorbidities (OR 0.48; CI 0.26–0.82). Conclusion: The study reports a relatively high prevalence of functional recovery for older COVID-19 patients admitted to sub-acute units. Additionally, it underlines the importance of targeting geriatrics syndromes, in particular frailty and delirium, for their possible effects on functional recovery. [ABSTRACT FROM AUTHOR]

The increasing presence of pharmaceutical products in municipality wastewaters has raised serious environmental concerns. Ozonation is one of the advanced oxidation processes that can degrade these substances, instead of simply transferring them from aqueous to another phase. Treatability studies applying ozonation to degrade benzodiazepine drugs are scarce. The aim of this investigation was to apply design of experiments (DoE) to optimize ozonation processes for removal of bromazepam, clonazepam, and diazepam from two effluents of municipal wastewater treatment plants (WWTP1 and WWTP2) both located in Rio de Janeiro City, Brazil. During a preliminary study using ultrapure water, OHº radicals were more efficient (removal efficiency greater than 99% (< LOQ) at pH = 10, 15 min) than O3 in degrading all psychoactive drugs (removal efficiency from 46 to 85% at pH = 4, 15 min). The optimum values for the tested variables were pH = 8.03; O3 specific dose = 4.8 mgO3.mgDOC−1; and O3 mass flow rate = 22.07 mgO3.min−1. The WWTP1 and WWTP2 effluents were treated under optimized conditions by ozonation in two effluent volumes (5L and 8L). When 8 L effluent was treated, the degradation of all benzodiazepine drugs was improved, due to the higher water column used, which favors the mass transfer of O3 from the gas phase to the liquid phase, promoting greater contact between oxidant and target compounds. Using a specific dose of 1.8 mgO3.mgDOC−1, more than 93% of all anxiolytic drugs were removed from 8 L of WWTP2 effluent, whereas for the WWTP1, more than 90% were removed using 2.7 times higher specific dose (4.8 mgO3.mgDOC−1). [ABSTRACT FROM AUTHOR]

Antidepressants, antiepileptics, mood stabilizers, and antipsychotics are extremely broadly used psychoactive drugs. These drug terms are universally used in the literature. However, the indications of these drugs have broadened substantially and overlap. The mismatch between drug classification and clinical uses causes a lot of confusion in communication and renders literature searches increasingly difficult. Therefore, we propose to drop the above terms altogether and replace them by simple mechanistic terms. Antidepressants are re-named as norepinephrine/serotonin (NE/5-HT) enhancers, antiepileptics comprising drugs with different mechanisms become neuronal inhibitors with pleiotropic effects (NIPEs), and antipsychotics become antagonists at multiple G protein–coupled receptors (mGPCR antagonists). Alkali metal ions, comprising lithium, are integrated into NIPEs. The terms "typical/first-generation/conventional" and "atypical/second-generation/non-conventional" antipsychotics should be dropped, because the original criterion for distinction, i.e., the presence and absence of extrapyramidal motor effects, respectively, is not valid anymore. The suggested changes in drug nomenclature have already been implemented into a recent textbook (Seifert R, Basic Knowledge of Pharmacology). The revised nomenclature ensures consistency with other fields of pharmacology and assignment of drug classes to indications without causing confusion. The authors acknowledge that the change in drug nomenclature is a cultural process that will take time and openly discuss the problems associated with the proposal. Ultimately, international learned societies will have to agree on a new nomenclature. [ABSTRACT FROM AUTHOR]

The paper presents literary and original data on the problems of falling for elderly patients. The relationship between the occurrence of a fall and the initiation of drug therapy with a known negative effect on the risk of falling is considered. Data on the frequency and structure of falls by patients with cardiovascular diseases over the age of 75 who received treatment at a multidisciplinary hospital are presented. The data analysis showed a tendency of fall prevalence: a fall was observed in 33.8% of patients in the first 5 days of the hospital stay. This may be associated with a high drug burden and the prescription of new drugs to the patient. The study noted that the therapy was chosen on the first day. Additional drugs were often prescribed, which led to the polypharmacy state. Analysis of individual groups of drugs allowed reliable confirmation of the relationship between the prescription of drugs that increase the fall risk and occurrence in relation to the ophthalmic form of β-blockers (p = 0.04). Polypharmacy as a risk factor of falling in gerontological patients, which was described in the scientific literature, also confirmed the negative effect in our study. Thus, patients who are newly administered drugs known to have negative effect on fall development can be attributed to the risk group for falling. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines "2C series" in monoaminergic neurons. Methods: After the exposure to "2C series", 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-ethylthiophenthylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I) or 2,5-dimethoxy-4-chlorophenethylamine (2C-C), we examined their neurotoxicity, morphological changes, and effects of concomitant exposure to 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine (METH), using cultured neuronal dopaminergic CATH.a cells and serotonin-containing B65 cells. Results: Single dose exposure to "2C series" for 24 h showed significant cytotoxicity as increase in lactate dehydrogenase (LDH) release from both monoaminergic neurons: 2C-T-7, 2C-C (EC50; 100 µM) > 2C-T-2 (150 µM), 2C-T-4 (200 µM) > 2C-I (250 µM) in CATH.a cells and 2C-T-7, 2C-I (150 µM) > 2C-T-2 (250 µM) > 2C-C, 2C-T-4 (300 µM) in B65 cells. The "2C series"-induced neurotoxicity in both cells was higher than that of MDMA or METH (EC50: ≥ 1–2 mM). In addition, apoptotic morphological changes were observed at relatively lower concentrations of "2C series". The concomitant exposure to non-toxic dose of MDMA or METH synergistically enhanced 2C series drugs-induced LDH release and apoptotic changes in B65 cells, but to a lesser extent in CATH.a cells. In addition, the lower dose of 2C-T-7, 2C-T-2 or 2C-I promoted reactive oxygen species production in the mitochondria of B65 cells, even at the early stages (3 h) without apparent morphological changes. Conclusion: The 2,5-dimethoxy-substitution of "2C series" induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons. [ABSTRACT FROM AUTHOR]

The consumption of psychoactive pharmaceuticals has increased worldwide, and wastewater treatment plants are not able to eliminate them from the effluent. An extensive review was carried out to assess the environmental risk (ERA model) based on secondary data about potential impacts on non-target organisms of seven psychoactive drugs consumed worldwide (alprazolam, bromazepam, citalopram, clonazepam, diazepam, lorazepam, and oxazepam). Risk quotients (RQs) were calculated according to the European Medicines Agency (EMA) on ERA of Medicinal Products For Human Use based on (i) the predicted and measured environmental concentrations (PEC and MEC, respectively) of the psychoactive drug in surface water, groundwater, and wastewater effluent and (ii) the predicted no-effect concentration (PNEC) derived from ecotoxicological assays or ECOSAR software. Furthermore, this study reviews and discusses non-standardized ecotoxicity assays, such as sublethal and behavioral effects on different organisms. In total, 903 MEC entries of psychoactive drugs and 162 data on ecotoxicological assays were gathered from the literature survey addressing behavioral effects (115), acute/chronic effects (35), and sublethal effects (12). Citalopram and diazepam were the only substances that are likely to pose an environmental risk (RQ > 1) to surface waters. Even though there is considerable amount of data on behavioral effects of psychoactive drugs to aquatic species, results are currently not integrated into the EMA risk assessment framework. The large amount of data on psychoactive drug concentrations and effects on non-target organisms collected, interpreted, and discussed in the present study should be used as a baseline for future improvement of ERA strategies. [ABSTRACT FROM AUTHOR]

A set of psychoactive drugs has been analyzed with the use of quantitative structure-activity/property relationships methods. The purpose of this study was to demonstrate both the common and differentiating characteristics of the above-mentioned chemical compounds, physicochemical as well as pharmacological based on the quantum chemical calculations and selected biological activity data and chromatographic retention parameters. During the study, the ab initio model of molecular modeling was performed and PCA, FA, and MLR as the types of chemometric approach. QSAR/QSPR models were proposed based on chosen statistically significant descriptors. The relationship between the structure and biological activity data was able to class and describe the psychoactive properties of the molecules studied. The applied chemometric approaches revealed the influential features of tested structures responsible for their pharmacological activity together with some additional physicochemical properties. [ABSTRACT FROM AUTHOR]

Breastfeeding women are excluded from clinical trials of psychoactive drugs because of ethical concerns. Animal testing, which often is predictive of adverse effects in humans, represents the only avenue available for assessing drug safety for human offspring exposed to drugs during lactation. I determined whether behavioral outcomes for children exposed during breastfeeding to antidepressants, anxiolytics, antipsychotics, anti-seizure medications, analgesics, sedatives, and marijuana can be predicted by rodent studies of offspring exposed to drugs during lactation. Animal data were available for only 10 of 80 CNS-active drugs canvassed. Behavioral deficits in adolescence or adulthood in rats and mice after various drug exposures during lactation included reductions in sexual behavior, increased anxiety, hyperactivity, and impaired learning and memory. Whether similar adverse effects will emerge in adulthood in children exposed to drugs during breastfeeding is unknown. Rodent research has the potential to forecast impairments in breastfed children long before information emerges from post-marketing reports and should be prioritized during preclinical drug evaluation by the FDA for new drugs and for drugs currently prescribed off-label for lactating women. [ABSTRACT FROM AUTHOR]

Rationale: Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders.Objectives: We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior.Methods: Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP). Subsequently, we assessed the effects of acute administration of scopolamine (0.125, 0.25, and 0.5 mg/kg), methamphetamine (0.25, 0.5, 1.25, and 2.5 mg/kg), ketamine (1.25, 2.5, 5, and 10 mg/kg), cannabidiol (1 and 3 mg/kg), WIN21255–2 (0.5, 075, and 1 mg/kg), and AM404 (0.25 and 0.5 mg/kg) on compulsive drinking in SIP.Results: Scopolamine reduced dose-dependent compulsive drinking in HD compared with LD rats in SIP. Methamphetamine induced a dose-dependent inverted U-curve effect in both groups, in which lower doses increased and higher doses reduced compulsive drinking in SIP. Ketamine, cannabidiol, WIN21255-2, and AM404 did not have any relevant effects in SIP.Conclusions: These data provide new evidence that low doses of scopolamine and intermediate doses of methamphetamine might therapeutically reduce compulsive behaviors and suggest that there is not a direct participation of the endocannabinoid system in compulsive behavior on SIP. The research in the underlying neurochemical mechanisms of these psychoactive drugs might provide an additional insight on new therapeutic targets in compulsive neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

This review focused on seven psychoactive drugs being six benzodiazepines (alprazolam, bromazepam, clonazepam, diazepam, lorazepam, and oxazepam) and one antidepressant (citalopram) widely consumed by modern society and detected in different aqueous matrices (drinking water, surface water, groundwater, seawater, estuary water, influent and effluent of wastewater treatment plants). The review included 219 selected scientific papers from which 1642 data/entries were obtained, each entry corresponding to one target compound in one aqueous matrix. Concentrations of all investigated drugs in all aqueous matrices varied from 0.14 to 840,000 ng L. Citalopram presented the highest concentrations in the aqueous matrices. Based on the Wilcoxon-Mann-Whitney test, differences between wastewater influents and effluents were not significant for most wastewater categories, suggesting that conventional wastewater treatment systems as such do not remove or remove partially these compounds. High-income countries showed much lower concentrations in surface water than the group formed by upper-middle-, lower-middle-, and low-income countries. Regarding analytical methods, solid-phase extraction (SPE) was by far the most used extraction method (83%) and performance liquid chromatography (HPLC) (73%) coupled to mass spectrometry (99%) the most common analytical method. Changes in behavior and in survival rates were the most common effects reported on bioindicators (aquatic species) due to the presence of these drugs in water. Concentrations of psychoactive drugs found in surface waters were most of the time within the range that caused measurable toxic effects in ecotoxicity assays. [ABSTRACT FROM AUTHOR]

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A multi-analyte method for the detection and quantification of 87 psychoactive drugs (antidepressants, antipsychotics, benzodiazepines, and z-drugs) in human hair has been developed and fully validated using the liquid chromatography-tandem mass spectrometry system. Due to the remarkable increase in requests of hair sample tests (such as for driver's license renewals, child custody, DFA cases, and postmortem toxicology), we focused on the development of a rapid sample preparation. About 20 mg of hair samples, previously washed and cut into snippets, was ultrasonicated with 700 μl of methanol. Samples were then directly analyzed using a 4000 QTRAP (AB SCIEX, Foster City, CA, USA) with an electrospray ionization (ESI) Turbo V Ion Source. The validation criteria parameters were satisfactory and in accordance with the international guidelines. All the compounds tested were successfully detected. One important aspect is the LODs in the low picogram per milligram concentration which may suggest a potential use of this method in cases of detection of single drug exposure. However, the LC-MS/MS method has been successfully applied for the analysis of postmortem cases ( n = 9). [ABSTRACT FROM AUTHOR]

The study was conducted in response to the lack of epidemiological data in recent time on the use of psychoactive substances by adolescents in metropolitan Lagos-a city unique for its socio-economic profile. We considered some methodological issues omitted in several previous studies. A total of 4,286 school pupils (mean age 15.2) were anonymously administered a Self-Report Questionnaire to ascertain a range of key drug use factors in lifetime and 1-year periods. The rate of use of most of the 14 substances investigated was much higher than reported in any other study on comparable population sample. We found that 61.8 and 32.1% of respondents have used one or more substances in their lifetime and in the past 1 year, respectively. High lifetime rates of use were found for common stimulants: coffee, kolanut, and prescription drugs (barbiturates and minor tranquilisers). The rate of use of proscribed addictive substances, cannabis, heroin, and cocaine, ranged between 4.0 and 4.8%. Missing data and non-response rates were few; however, social acquiescence, under and over reporting, could be mitigant to estimation of rates and patterns of use. We advocate properly articulated school-based educative programmes that can facilitate drug demand reduction. [ABSTRACT FROM AUTHOR]

Background: Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as a cheaper alternative to other classified recreational drugs. Aims: We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities. Methods: Because of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem. Discussion and Conclusions: Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the relationship between health-related quality of life (HRQOL) and tobacco consumption in adult individuals (over the age of 15). The study was based on individual data from the City of Madrid Health Survey (ESCM05). Subjects were divided into three groups according to tobacco consumption: smokers, nonsmokers, and ex-smokers. HRQOL was measured using the COOP/WONCA quality-of-life vignettes. A multivariate adjustment with multinomial logistic regression was made, including the following as covariables: sociodemographic characteristics, comorbidities, drug use, and lifestyles. A total of 7341 individuals were interviewed (53.7% women), with an average age of 46.7 (SD = 19.02) years. The percentage of smokers was 27%, that of ex-smokers was 16.5%, and that of nonsmokers was 56.5%. There were no significant differences between smokers, ex-smokers, and nonsmokers in the raw scores obtained as totals from the COOP/WONCA questionnaire. Multivariate analysis revealed that smokers consume more antidepressant drugs (OR = 1.54, 95% CI = 1.09–2.16) and tranquilizers (OR = 1.91, 95% CI = 1.45–2.51), drink more alcohol (OR = 2.55, 95% CI = 2.11–3.08), get less physical exercise (OR = 1.33, 95% CI = 1.11–1.60), and have a lower quality of life (OR = 1.02, 95% CI = 1.00–1.04) than nonsmokers. Following adjustment for a significant number of covariables, sociodemographic as well as health-related, smokers consume more antidepressant drugs and tranquilizers, drink more alcohol, get less physical exercise, and demonstrate a lower HRQOL than nonsmokers. [ABSTRACT FROM AUTHOR]

This contribution to the “antidepressant debate” focuses on the validity of randomized controlled trials (RCTs). We argue that: (a) made-up psychiatric diagnostic categories destroy the purpose and logic of the RCT as a medical experiment, (b) RCTs do everything possible to methodologically stamp out high placebo response rates rather than reveal their clinical implications, (c) assessing a psychoactive drug’s effects greatly exceeds the RCT’s purpose, requiring substantial investigation on normal volunteers, and (d) adverse drug reactions remain understudied, under-recognized, and underappreciated, in parallel with the muting of subjects’ voice and the reliance on surrogate measures of efficacy. The standard psychopharmacotherapy RCT has lost virtually all clinical and scientific relevance, and needs complete revamping. The backdrop for the discussion is American biopsychiatry’s insistence that personal difficulties must be viewed as the expression of idiopathic somatic diseases and the pharmaceutical industry’s dominance of the entire drug treatment research enterprise. [ABSTRACT FROM AUTHOR]

A method has been developed which permits monkeys to self-administer drug solutions, at will, through indwelling intravenous catheters. Psychological dependence on the effects of a drug occurs when a naive monkey voluntarily initiates and maintains self-administration of the drug. If, in addition to psychological dependence, the drug also produces psychotoxicity, either directly or upon abrupt withdrawal, it has a potential abuse liability. In the present study monkeys developed psychological dependence on morphine, codeine, cocaine, d-amphetamine, pentobarbital, ethanol, and caffeine. All of these drugs except caffeine produced psychotoxicity. Monkeys did not develop psychological dependence on nalorphine, morphine-nalorphine mixtures, chlorpromazine, mescaline or physiological saline. [ABSTRACT FROM AUTHOR]

Cannabis products (marijuana, weed, hashish) are among the most widely abused psychoactive drugs in the world, due to their euphorigenic and anxiolytic properties. Recently, hair analysis is of great interest in analytical, clinical, and forensic sciences due to its non-invasiveness, negligible risk of infection and tampering, facile storage, and a wider window of detection. Hair analysis is now widely accepted as evidence in courts around the world. Hair analysis is very feasible to complement saliva, blood tests, and urinalysis. In this review, we have focused on state of the art in hair analysis of cannabis with particular attention to hair sample preparation for cannabis analysis involving pulverization, extraction and screening techniques followed by confirmatory tests (e.g., GC–MS and LC–MS/MS). We have reviewed the literature for the past 10 years' period with special emphasis on cannabis quantification using mass spectrometry. The pros and cons of all the published methods have also been discussed along with the prospective future of cannabis analysis. [ABSTRACT FROM AUTHOR]