•Emergence of new psychoactive substances require new approaches for drug monitoring.•Voltammetric studies to understand the oxidative mechanism of piperazine derivatives.•Crucial role of aromatic ...amine, present in molecular’ structures, on oxidative profiles.•Contribution to predict metabolites and development of new analytical methods.
The emergence of a large number of new psychoactive substance (NPS) on the global drug market poses a significant risk to public health and a challenge to drug control systems. Over the last decades, electrochemical sensing of illicit drugs has experienced a very significant growth, since these techniques can provide fast, portable, sensitive and low-cost detection alternatives for the analysis of drugs, metabolites and/or transformation products in different matrices.
To understand and clarify the oxidative mechanism of piperazine designer drugs, the voltammetric profile of psychoactive piperazine derivatives 1-phenylpiperazine (PhPIP), 3-chlorophenylpiperazine (mCPP), 3-trifluoromethylphenylpiperazine (TFMPP), 4-fluorophenylpiperazine (pFPP) and benzylpiperazine (BZP) has been investigated at a glassy carbon electrode. The data found showed the crucial role of the aromatic amine, present in PhPIP, mCPP, pFPP and TFMPP molecular’ structures, on the oxidative profiles. The voltammetric behavior of BZP is quite different from those found for the other piperazines under study due to the nature of the amine group present in BZP molecular’ structure, benzylic instead of an aromatic amine.
This work can be a helpful contribution to the ability to predict and identify metabolites and the development of new analytical approaches that can allow the rapid and specific quantitative detection of psychoactive piperazine derivatives.
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 (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.
•Psychiatric implication of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings.•Report on the main classes of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) consumed in custodial settings.•Report on the primary modalities of substance intake in prison.•It provides guidance and suggestions on how to strengthen harm reduction programs, enhance and expand access to treatment services.
•Several MDA analogs exhibited a pharmacological profile comparable to MDMA.•3C-BOH and N,α-DEPEA are dopaminergic stimulants similar to amphetamine.•DPIA displayed only minor monoaminergic activity ...compared to amphetamine.
3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The β‑methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 µM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. Furthermore, several compounds interacted with adrenergic receptors and the trace amine-associated receptor 1 (TAAR1) in the micromolar range. The pharmacological profiles of some fluorinated and nonfluorinated MDA analogs resemble the profile of MDMA. In contrast, 3C-BOH and N,α-DEPEA displayed more pronounced dopaminergic activity similar to amphetamine. Pharmacokinetics and pharmacodynamics studies are necessary to better establish the risks and therapeutic potential of the tested drugs.
New psychoactive substances (NPS), often referred as 'legal highs' or 'designer drugs', are derivatives and analogs of existing psychoactive drugs that are introduced in the recreational market to ...circumvent existing legislation on drugs of abuse. This work aims to review the state-of-the-art regarding chemical, molecular pharmacology, and in vitro and in vivo data on toxicokinetics of the potent synthetic cathinone α-pyrrolidinovalerophenone (α-PVP or flakka or zombie drug). Chemical, pharmacological, toxicological, and clinical effects of α-PVP were searched in PubMed (U.S. National Library of Medicine) and governmental websites without limitation of the period. α-PVP is a wide spread and easy to get special type of synthetic cathinone with seemingly powerful cocaine-like stimulant effects, high brain penetration, high liability for abuse and with increased risk of adverse effects such as tachycardia, agitation, hypertension, hallucinations, delirium, mydriasis, self-injury, aggressive behavior, and suicidal ideations. α-PVP undergoes extensive metabolism via different pathways and the α-PVP itself or its metabolites β-hydroxy-α-PVP and α-PVP lactam represent the main targets for toxicological analysis in urine. There is a limited knowledge regarding the short- and long-term effects of α-PVP and metabolites, and pharmacogenetic influence, hence further clinical and forensic toxicological studies are required. Moreover, since α-PVP cannot be detected with classic routine analysis procedures, statements on the frequency of their consumption cannot be made.
The word "cannabinoid" refers to every chemical substance, regardless of structure or origin, that joins the cannabinoid receptors of the body and brain and that have similar effects to those ...produced by the Cannabis plant and based on their source of production, cannabinoids can be classified into endocannabinoids, phytocannabinoids and synthetic cannabinoids. Synthetic cannabinoids represent the largest class of drugs detected through the EU Early Warning System with a total of 190 substances notified from 2008 to 2018 and about 280 have been reported worldwide to the United Nations Office on Drugs and Crime. Sprayed on natural herb mixtures with the aim to mimic the euphoria effect of cannabis and sold as "herbal smoking blends" or "herbal incense" under brand names like "Spice" or "K2", synthetic cannabinoids are available from websites for the combination with herbal materials or more recently, for the use in e-cigarettes. Currently labeled as "not for human consumption" to circumvent legislation, their legal status varies by country with many government institutions currently pushing for their control. However, due to the emergence of new substances, it requires a constant update of the list of controlled drugs. Little is known about how these substances work and their toxic effects in humans and the same product could vary not only in the amount and in the type of substance added. In the last years, synthetic cannabinoids have been associated with deaths and acute intoxications in Europe and, despite a range of new measures introduced in this area, continue to represent a challenge to current drug policy models. These synthetic substances are much more potent than natural cannabis, as well as displayed greater efficacy, acting as full agonists at the cannabinoid receptors. It is possible that, along with being highly potent, some may also have long half-lives, potentially leading to a prolonged psychoactive effect. The present work provides a review on existing literature about the development of synthetic cannabinoids as substances of abuse, current patterns of abuse and their legal status, chemical classification, and some pharmacological and toxicological properties.
Database-driven suspect screening has proven to be a useful tool to detect new psychoactive substances (NPS) outside the scope of targeted screening; however, the lack of retention times specific to ...a liquid chromatography (LC) system can result in a large number of false positives. A singular stream-lined, quantitative structure-retention relationship (QSRR)-based retention time prediction model integrating multiple LC systems with different elution conditions is presented using retention time data (n = 1281) from the online crowd-sourced database, HighResNPS. Modelling was performed using an artificial neural network (ANN), specifically a multi-layer perceptron (MLP), using four molecular descriptors and one-hot encoding of categorical labels. Evaluation of test set predictions (n = 193) yielded coefficient of determination (R2) and mean absolute error (MAE) values of 0.942 and 0.583 min, respectively. The model successfully differentiated between LC systems, predicting 54%, 81% and 97% of the test set within ±0.5, ±1 and ±2 min, respectively. Additionally, retention times for an analyte not previously observed by the model were predicted within ±1 min for each LC system. The developed model can be used to predict retention times for all analytes on HighResNPS for each participating laboratory's LC system to further support suspect screening.
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•A retention time prediction model was developed incorporating multiple LC systems.•The model was trained using the retention times of new psychoactive substances.•Retention times were obtained from the crowd-sourced database, HighResNPS.•A singular model demonstrated improved performance over individual models.•The model can be used to predict retention times for unique entries on HighResNPS.
Emerging new psychoactive substances (NPS) poses a great risk to public health. Analyzing these large numbers of NPS and other associated substances often relies on liquid chromatography coupled to ...triple quadrupole mass spectrometry (LC-QqQ-MS) with multiple-reaction monitoring (MRM) mode. However, the differentiation of critical pairs, coeluted isobaric and/or isomeric species, is one of the challenges for this analytical platform. MRM transitions with poor selectivity can jeopardize accurate quantification and lead to biased interpretation. Herein, we refined a novel workflow for developing an MRM-based method with in-house CriticalPairFinder and TransitionFinder tools for the effective identification of unique and selective MRM transitions. Transitions selected by TransitionFinder showed much better accuracies than those selected only by fragment abundance in some mixtures of critical pairs. Using the proposed analytical strategy, a method that can simultaneously determine 219 NPS and 65 other substances across a variety of NPS classes in urine samples was developed, validated and applied to analyze clinical urine samples. This automated workflow is anticipated to facilitate method development for analyzing complex analytes while considering selectivity.
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•Presentation of a novel workflow for choosing selective MRM transitions.•Development of CriticalPairFinder tool for effective identification of poor separated pairs.•Better accuracies for MRM transitions obtained from developed TransitionFinder.•Development of analytical method for determining 284 abused substances.•This workflow facilitates method development for complex analytes with considering selectivity.
•The current classification of psychoactive substances needs to be urgently reviewed.•A classification of NPS exclusively based on their chemical structure is proposed.•The chemical subcategories ...have been thoroughly revised and discussed to be consistent.•The CAS number/chemical structure of NPS should be always provided.
This work comprehensively reviews some fundamental concepts about drugs, especially focusing on new psychoactive substances (NPS), and their typical classifications based on either their effects (hallucinogens, stimulants or depressants), their origin (natural, synthetic, or semisynthetic), or legal situation (lawful, illicit, or unregulated). These classifications are highly useful in the medicine/legal field, but completely useless for the chemical determination of drugs. Hence, a classification of NPS based on their chemical composition is revised and discussed. This classification seeks to merge those recent and dispersed chemical groupings of NPS found in scientific literature and/or health/drugs reports from World/European/American Institutions facing the illicit use of drugs (WHO, UNODC, EMCDDA, OEDA, DEA, etc.) into a unique general classification, which might be useful for every forensic practitioner/researcher dealing with the identification of new psychoactive substances.
The consumption of psychoactive substances is considered a growing problem in many communities. Moreover, new psychoactive substances (NPS) designed as (legal) substitutes to traditional illicit ...drugs are relatively easily available to the public through e-commerce and retail shops, but there is little knowledge regarding the extent and actual use of these substances. This study aims to gain new and complementary information on NPS and traditional illicit drug use at six music festivals across Europe by investigating wastewater and pooled urine. Samples were collected, between 2015 and 2018, at six music festivals across Europe with approximately 465.000 attendees. Wastewater samples were also collected during a period not coinciding with festivals. A wide-scope screening for 197 NPS, six illicit drugs and known metabolites was applied using different chromatography-mass spectrometric strategies. Several illicit drugs and in total 21 different NPS, mainly synthetic cathinones, phenethylamines and tryptamines, were identified in the samples. Ketamine and the traditional illicit drugs, such as amphetamine-type stimulants, cannabis and cocaine were most abundant and/or frequently detected in the samples collected, suggesting a higher use compared to NPS.
The analyses of urine and wastewater is quick and a high number of attendees may be monitored anonymously by analysing only a few samples which allows identifying the local profiles of use of different drugs within a wide panel of psychoactive substances. This approach contributes to the development of an efficient surveillance system which can provide timely insight in the trends of NPS and illicit drugs use.
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•Substance use was assessed at music festivals across six European countries.•Urine and wastewater analyses can provide timely complementary information.•Wastewater-based epidemiology provides information on the pattern of drug use at festivals.•Specific local patterns of substance use were identified.•NPS were identified but cocaine, MDMA, cannabis and ketamine were most frequently detected.
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