Target and Nontarget Screening to Support Capacity Scaling for Substance Use Assessment through a Statewide Wastewater Surveillance Network in New York.

Wastewater-based epidemiology (WBE) has been widely implemented around the world as a complementary tool to conventional surveillance techniques to inform and improve public health responses. Currently, wastewater surveillance programs in the U.S. are evaluating integrated approaches to address public health challenges across multiple domains, including substance abuse. In this work, we demonstrated the potential of online solid-phase extraction coupled with liquid chromatography-high-resolution mass spectrometry to support targeted quantification and nontargeted analysis of psychoactive and lifestyle substances as a step toward understanding the operational feasibility of a statewide wastewater surveillance program for substance use assessment in New York. Target screening confirmed 39 substances in influent samples collected from 10 wastewater treatment plants with varying sewershed characteristics and is anticipated to meet the throughput demands as the statewide program scales up to full capacity. Nontarget screening prioritized additional compounds for identification at three confidence levels, including psychoactive substances, such as opioid analgesics, phenethylamines, and cathinone derivatives. Consumption rates of 12 target substances detected in over 80% of wastewater samples were similar to those reported by previous U.S.-based WBE studies despite the uncertainty associated with back-calculations. For selected substances, the relative bias in consumption estimates was sensitive to variations in monitoring frequency, and factors beyond human excretion (e.g., as indicated by the parent-to-metabolite ratios) might also contribute to their prevalence at the sewershed scale. Overall, our study marks the initial phase of refining analytical workflows and data interpretation in preparation for the incorporation of substance use assessment into the statewide wastewater surveillance program in New York.

Metabolism and cytotoxicity studies of the two hallucinogens 1cP-LSD and 4-AcO-DET in human liver and zebrafish larvae models using LC-HRMS/MS and a high-content screening assay.

The continuous emergence of new psychoactive substances (NPS) attracted a great deal of attention within recent years. Lately, the two hallucinogenic NPS 1cP-LSD and 4-AcO-DET have appeared on the global market. Knowledge about their metabolism to identify potential metabolic targets for analysis and their cytotoxic properties is lacking. The aim of this work was thus to study their in vitro and in vivo metabolism in pooled human liver S9 fraction (pHLS9) and in zebrafish larvae (ZL) by means of liquid chromatography-high-resolution tandem mass spectrometry. Monooxygenases involved in the initial metabolic steps were elucidated using recombinant human isozymes. Investigations on their cytotoxicity were performed on the human hepatoma cell line HepG2 using a multiparametric, fluorescence-based high-content screening assay. This included measurement of CYP-enzyme mediated effects by means of the unspecific CYP inhibitor 1-aminbenzotriazole (ABT). Several phase I metabolites of both compounds and two phase II metabolites of 4-AcO-DET were produced in vitro and in vivo. After microinjection of 1cP-LSD into the caudal vein of ZL, three out of seven metabolites formed in pHLS9 were also detected in ZL. Twelve 4-AcO-DET metabolites were identified in ZL after exposure via immersion bath and five of them were found in pHLS9 incubations. Notably, unique metabolites of 4-AcO-DET were only produced by ZL, whereas 1cP-LSD specific metabolites were found both in ZL and in pHLS9. No toxic effects were observed for 1cP-LSD and 4-AcO-DET in HepG2 cells, however, two parameters were altered in incubations containing 4-AcO-DET together with ABT compared with incubations without ABT but in concentrations far above expected in vivo concentration. Further investigations should be done with other hepatic cell lines expressing higher levels of CYP enzymes.

Exploring a Lux® i-Amylose-3 column in normal phase and polar-organic mode for chiral separation of cathinone derivatives and pyrovalerones using high-performance liquid chromatography.

Each year, new psychoactive substances appear on the global drug market leading to constant changes. Most of these compounds with stimulating effect possess a chiral center, thus leading to two enantiomers with presumably different pharmacological properties. Among them, synthetic cathinones, often misleadingly traded as "bath salts," play an important role. There is little knowledge about the distinct effect of the enantiomers. The aim of this study was to test a commercially available Lux® i-Amylose-3 column by HPLC-UV for enantiorecognition of cathinone derivatives. Overall, 80 compounds were tested in normal phase mode, where 75 substances were separated under initial conditions. After method optimization, at least partial separation was achieved for the remaining compounds. The same set of substances was measured in polar-organic mode, where 63 analytes were resolved into their enantiomers under initial conditions with very short retention times. Both modes showed complementary results for the individual compounds. Furthermore, the tested methods proved to be suitable for differentiation of positional isomers, which can be useful for drug checking programs. All measurements were carried out under isocratic conditions, and intraday and interday repeatability tests were performed.

New trends of drug abuse in custodial settings: A systematic review on the misuse of over-the-counter drugs, prescription-only-medications, and new psychoactive substances.

The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused with caution (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes.

Screening of Astec® CHIRALDEX™ G-PN and LIPODEX™ D gas chromatography columns for enantioseparation of amphetamine derivatives.

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-ß-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.

Qualitative transformations of street-seized ecstasy over a decade: A case study in Rio de Janeiro (Brazil).

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.

Analytical and behavioral characterization of 1-dodecanoyl-LSD (1DD-LSD).

1-Acetyl-N,N-diethyllysergamide (1A-LSD, ALD-52) was first synthesized in the 1950s and found to produce psychedelic effects similar to those of LSD. Evidence suggests that ALD-52 serves as a prodrug in vivo and hydrolysis to LSD is likely responsible for its activity. Extension of the N1-alkylcarbonyl chain gives rise to novel lysergamides, which spurred further investigations into their structure-activity relationships. At the same time, ALD-52 and numerous homologues have emerged as recreational drugs ("research chemicals") that are available from online vendors. In the present study, 1-dodecanoyl-LSD (1DD-LSD), a novel N1-acylated LSD derivative, was subjected to analytical characterization and was also tested in the mouse head-twitch response (HTR) assay to assess whether it produces LSD-like effects in vivo. When tested in C57BL/6J mice, 1DD-LSD induced the HTR with a median effective dose (ED50) of 2.17 mg/kg, which was equivalent to 3.60 µmol/kg. Under similar experimental conditions, LSD has 27-fold higher potency than 1DD-LSD in the HTR assay. Previous work has shown that other homologues such as ALD-52 and 1-propanoyl-LSD also have considerably higher potency than 1DD-LSD in mice, which suggests that hydrolysis of the 1-dodecanoyl moiety may be comparatively less efficient in vivo. Further investigations are warranted to determine whether the increased lipophilicity of 1DD-LSD causes it to be sequestered in fat, thereby reducing its exposure to enzymatic hydrolysis in plasma and tissues. Further clinical studies are also required to assess its activity in humans and to test the prediction that it could potentially serve as a long-acting prodrug for LSD.

Target analysis of psychoactive drugs in oral fluid by QuEChERS extraction and LC-MS/MS.

This study aimed to validate a modified QuEChERS method, followed by liquid chromatography-tandem mass spectrometry, for the determination of 51 psychoactive substances and screening of 22 ones in oral fluid from electronic dance music party (EDM) attendees. Unstimulated oral fluid was collected in a polypropylene tube and stored in a glass vial at -20 ºC. The sample was extracted with acetonitrile:water and MgSO4/NaOAc, followed by cleanup with primary secondary amine and MgSO4. The effectiveness of the sample storage conditions was shown to be comparable to when the Quantisal™ buffer was used, with no substantial concentration loss (< 15%) for all the substances after up to 72 hours at -20º C. The method was satisfactorily validated, with limits of detection (LOD) and quantification (LOQ) ranging from 0.04 to 0.5 ng/mL and 0.1-1.5 ng/mL, respectively, and was applied to the analysis of 62 real samples. The main substances detected were 3,4-methylenedioxymethamphetamine (MDMA) (<0.5-829 ng/mL) and/or methylenedioxyamphetamine (MDA) (10.1 - 460.6 ng/mL), found in 27 samples, and cocaine (13.0-407.3 ng/mL) and its metabolites (benzoylecgonine 0.17-214.1 ng/mL; ecgonine methyl ester 1.8-150.1 ng/mL) in eight samples. Methamphetamine (11-439 ng/mL) was detected in eight samples, along with MDMA and MDA; eutylone was detected in two cases (4.7 and 24.1 ng/mL) reported as "ecstasy" ingestion. A comparison between self-reported drug use and results of oral fluid analysis indicated that the use of illicit substances is often underreported among EDM attendees, who are often unaware of the substances they consume.

Toxicity of butylone and its enantiomers to Daphnia magna and its degradation/toxicity potential using advanced oxidation technologies.

Butylone (BTL) is a chiral synthetic cathinone available as a racemate and reported as contaminant in wastewater effluents. However, there are no studies on its impact on ecosystems and possible enantioselectivity in ecotoxicity. This work aimed to evaluate: (i) the possible ecotoxicity of BTL as racemate or its isolated (R)- and (S)- enantiomers using Daphnia magna; and (ii) the efficiency of advanced oxidation technologies (AOTs) in the removal of BTL and reduction of toxic effects caused by wastewaters. Enantiomers of BTL were obtained by liquid chromatography (LC) using a chiral semi-preparative column. Enantiomeric purity of each enantiomer was > 97 %. For toxicity assessment, a 9-day sub-chronic assay was performed with the racemate (at 0.10, 1.0 or 10 µg L-1) or each enantiomer (at 0.10 or 1.0 µg L-1). Changes in morphophysiological, behavioural, biochemical and reproductive endpoints were observed, which were dependent on the form of the substance and life stage of the organism (juvenile or adult). Removal rates of BTL in spiked wastewater (10 µg L-1) treated with different AOTs (ultraviolet, UV; ozonation, O3; and UV/O3) were similar and lower than 29 %. The 48 h D. magna acute toxicity assays demonstrated a reduction in the toxicity of the treated spiked effluents, but no differences were found amongst AOTs treatments. These results warn for the contamination and negative impact of BTL on ecosystems and highlight the need for efficient removal processes.

Smartphone swabs as an emerging tool for toxicology testing: a proof-of-concept study in a nightclub.

OBJECTIVES: Smartphones have become everyday objects on which the accumulation of fingerprints is significant. In addition, a large proportion of the population regularly uses a smartphone, especially younger people. The objective of this study was to evaluate smartphones as a new matrix for toxico-epidemiology. METHODS: This study was conducted during two separate events (techno and trance) at an electronic music nightclub in Grenoble, France. Data on reported drug use and whether drugs were snorted directly from the surface of the smartphone were collected using an anonymous questionnaire completed voluntarily by drug users. Then, a dry swab was rubbed for 20 s on all sides of the smartphone. The extract was analyzed by liquid chromatography coupled to tandem mass spectrometry on a Xevo TQ-XS system (Waters). RESULTS: In total, 122 swabs from 122 drug users were collected. The three main drugs identified were MDMA (n=83), cocaine (n=59), and THC (n=51). Based on declarative data, sensitivity ranged from 73 to 97.2 % and specificity from 71.8 to 88.1 % for MDMA, cocaine, and THC. Other substances were identified such as cocaine adulterants, ketamine, amphetamine, LSD, methamphetamine, CBD, DMT, heroin, mescaline, and several NPS. Numerous medications were also identified, such as antidepressants, anxiolytics, hypnotics, and painkillers. Different use patterns were identified between the two events. CONCLUSIONS: This proof-of-concept study on 122 subjects shows that smartphone swab analysis could provide a useful and complementary tool for drug testing, especially for harm-reduction programs and toxico-epidemiolgy studies, with acceptable test performance, despite declarative data.

Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

Efficient magnetic solid-phase extraction, UPLC-MS/MS detection, and consumption assessment of five trace psychoactive substances.

Wastewater-based epidemiology (WBE) has become an objective and updated surveillance strategy for monitoring and estimating consumption trends of psychoactive substances (PSs) in the population. Firstly, magnetic shrimp shell biochar-based adsorbent (DZMBC) was synthesized and employed for extraction trace PSs from municipal wastewater. Proper pyrolysis temperature and increased KOH activator content favored the pore structure and surface area, thus facilitating extraction. DZMBC delivered exceptional extraction performance such as pH stability, anti-interference property, fast magnetic separation ability, reusability, and reproducibility. Then, a method based on magnetic solid-phase extraction (MSPE) followed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed, validated, and utilized for the quantitative determination of five PSs in real wastewater samples. Methodological validation results indicated a favorable linearity, low method limits of detection (1.00-4.75 ng/L), and good precisions (intra-day and inter-day relative standard deviations < 4.8%). Finally, an objective snapshot of Chongqing drug use and consumption pattern was obtained. Methamphetamine (MAMP) and 3,4-methylenedioxymethamphetamine (MDMA) were the prevalent illegal drugs in local. Both concentrations and per capita consumption of MDMA displayed a change (P < 0.05) between July and September, while no statistical differences were observed for each week.

Synthetic Cathinones: Epidemiology, Toxicity, Potential for Abuse, and Current Public Health Perspective.

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as ß-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies.

Target and suspect screening of psychoactive substances in seizures and oral fluid exploiting retention time prediction and LC-MS/MS analysis.

BACKGROUND: Novel psychoactive substances (NPS) are a group of substances, mainly of synthetic origin, characterized by toxicological properties extremely dangerous. The main difficulty in recognizing NPS in seizures and biological samples lies in their dynamic nature, related to the continuous synthesis and introduction on the market of new drugs, often with very similar structures to existing ones. The aim of this study was the creation of a robust and versatile method for the analysis of traditional drugs and NPS in different matrices. RESULTS: Both target analysis and suspect screening methodologies were developed. The strategy used for suspect screening allowed to collect data through a scheduled multi reaction monitoring (sMRM) survey which triggered the collection of enhanced product ion (EPI) spectra when a compound met information dependent acquisition (IDA) criteria. The retention time of the different drugs, which was crucial to define the sMRM survey scan parameters, was predicted with a Quantitative Structure Retention (Chromatographic) Relationship (QSRR) model by Multiple Linear Regression. The model was validated through the evaluation of training set predictions, an external validation set and a leave-one out strategy; the results showed that the method fit for its purpose. The target method was validated in oral fluid as a testing matrix, with excellent results in term of recovery, accuracy, precision and matrix effect. Finally, the performances of the suspect method were evaluated by analysing a mixture containing 8 reference standards not included in the initial dataset, as well as seizures and real oral fluid samples. Four NPS were putatively identified in the analysed samples. SIGNIFICANCE: The advantage of the proposed approach is the possibility of quantifying 65 classical drugs of abuse and NPS and, at the same time, detect and putatively identify 146 additional drugs in one single LC-MS/MS run. This is an innovative strategy for multi analyte detection and enables detection of low concentrations of drugs in complex biological matrices such as oral fluid. Considering the highly dynamic drug market, a strength of this strategy is that the analytical method can be kept up to date through the addition of new compounds based on the last drug monitoring bodies alerts without the need of authentic standards.

A critical review of workplace drug testing methods for old and new psychoactive substances: Gaps, advances, and perspectives.

Workplace drug testing (WDT) is essential to prevent drug abuse disorders among the workforce because it can impair work performance and safety. However, WDT is limited by many challenges, such as urine adulteration, specimen selection, and new psychoactive substances (NPS). This review examined the issues related to WDT. Various scientific databases were searched for articles on WDT for drug detection published between 1986 (when WDT started) and January 2024. The review discussed the history, importance, and challenges of WDT, such as time of specimen collection/testing, specimen adulteration, interference in drug testing, and detection of NPS. It evaluated the best methods to detect NPS in forensic laboratories. Moreover, it compared different techniques that can enhance WDT, such as immunoassays, targeted mass spectrometry, and nontargeted mass spectrometry. These techniques can be used to screen for known and unknown drugs and metabolites in biological samples. This review assessed the strengths and weaknesses of such techniques, such as their validation, identification, library search, and reference standards. Furthermore, this review contrasted the benefits and drawbacks of different specimens for WDT and discussed studies that have applied these techniques for WDT. WDT remains the best approach for preventing drug abuse in the workplace, despite the challenges posed by NPS and limitations of the screening methods. Nontargeted techniques using high-resolution liquid chromatography-mass spectrometry (MS)/gas chromatography-tandem MS can improve the detection and identification of drugs during WDT and provide useful information regarding the prevalence, trends, and toxicity of both traditional and NPS drugs. Finally, this review suggested that WDT can be improved by using a combination of techniques, multiple specimens, and online library searches in case of new NPS as well as by updating the methods and databases to include new NPS and metabolites as they emerge. To the best of the author's knowledge, this is the first review to address NPS as an issue in WDT and its application and propose the best methods to detect these substances in the workplace environment.

A comparative study of old versus novel psychoactive substances on craving, perceived stigma and suicidal risk among rural-dwelling patients with substance abuse.

WHAT IS KNOWN ON THE SUBJECT?: According to recent estimates, 10.4% of adults are patients with substance abuse, which is almost double the global rate. Rural areas are typically marginalized, compounded by a lack of access to mental health care, creating a startling disparity in suffering from drug use issues among rural cohorts. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Drawing on data from a descriptive comparative design would provide a distinctive picture related to the similarities and/or differences in relation to craving and how it affects perceived stigma and suicidal risk among patients using old versus novel psychoactive substances. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Substance abuse is a leading public health concern that forces nurses to encompass it into their agendas to tackle this looming problem. Addiction rehabilitation services are frequently run by nurses. They are well-versed in supporting patients during their journey to recovery and enabling them to adjust to a new lifestyle. ABSTRACT: INTRODUCTION: Substance use disorder is a leading public health concern that currently, nations regulatory agencies are grappled with. The noticeable difference in the chemical structures between old and novel psychoactive substances can result in significant clinical complications among patients with substance abuse. AIM: The study aims to compare substance craving, perceived stigma and suicidal risk among patients addicted to old and novel psychoactive substances (NPS). METHOD: A descriptive comparative design was adopted on a sample of 105 patients with substance use who completed The Penn Alcohol Craving Scale (PACS), The Perceived Stigma of Addiction Scale (PSAS) and Suicide Probability Scale (SPS). DISCUSSION: Most participants were male, with 89.5% in the old addictive substance group and 93.8% in the new addictive substance group. A statistically significant difference in the NPS groups' perceptions of stigma (23.4 ± 5.3) compared to the old addictive substance group (20.6 ± 4.2), (t = 3.037, p = .003). IMPLICATION FOR PRACTICE: Participants in the new substance group report more suicidal ideation, negative self-evaluation and hostility than those in the old substance group. Policies and practices should be tailored to the type of drug used and potential risk factors to avoid suicide among patients with substance abuse.

Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats.

BACKGROUND: The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted. METHODS: By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties. RESULTS: 2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs. CONCLUSIONS: This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users.

Occurrence, ecotoxicity and ecological risks of psychoactive substances in surface waters.

Psychoactive substances (PSs) represent a subset of emerging contaminants. Their widespread production and utilization contribute to a growing ecological burden and risk on a global scale. Conventional wastewater treatment methods have proven insufficient in adequately removing psychoactive substances, leading to their occurrence in surface water ecosystems worldwide. As of present, however, a thorough understanding of their geographical prevalence and distribution patterns remains elusive. Further, in the existing literature, there is a scarcity of comprehensive overviews that systematically summarize the toxicity of various psychoactive substances towards aquatic organisms. Through summarizing almost 140 articles, the present study provides an overview of the sources, pollution status, and biotoxicity of psychoactive substances in surface waters, as well as an assessment of their ecological risks. Concentrations of several psychoactive substances in surface waters were found to be as high as hundreds or even thousands of ng·L-1. In parallel, accumulation of psychoactive substances in the tissues or organs of aquatic organisms was found to potentially cause certain adverse effects, including behavioral disorders, organ damage, and DNA changes. Oxidative stress was found to be a significant factor in the toxic effects of psychoactive substances on organisms. The application of the risk quotient approach indicated that psychoactive substances posed a medium to high risk in certain surface water bodies, as well as the need for sustained long-term attention and management strategies.

Crystal structure and analytical profile of 1,2-diphenyl-2-pyrrolidin-1-ylethanone hydrochloride or `α-D2PV': a synthetic cathinone seized by law enforcement, along with its diluent sugar, myo-inositol.

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT-IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant complete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hydrochloride hemihydrate or 1-(2-oxo-1,2-diphenylethyl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+·Cl-·0.5H2O, (I), a synthetic cathinone called `α-D2PV', and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) interesting hydrogen bonding observed in pairwise interactions by the drug molecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π-π interactions in the case of the phenyl rings of the drug which are of two different types, namely, π-π stacking and edge-to-π. Finally, the inositol crystallizes with Z' = 2 and the resulting diastereoisomers were examined by overlay techniques.